INTRODUCTION AND OVERVIEW NG MEMBRANE FUNCTION
The plasma membrane, also known as the cell membrane, serves as a barrier in all cells,
dividing the cell's interior from its external surroundings. In bacterial and plant cells, there is
an additional outer layer called the cell wall, which is connected to the outer surface of
the plasma membrane.
Membrane Functions
1. Compartmentalization
a. Cell membranes create separate compartments like the plasma, nuclear, and
cytoplasmic membranes. These compartments facilitate specialized
activities, shield against external interference, and allow for independent
regulation of cellular processes due to their distinct contents.
2. Scaffold for biochemical activities
a. Membranes function as both compartments and organized structures,
enabling more effective interactions compared to random collisions in
solution.
3. Providing a selectively permeable barrier
a. Membranes act as selective barriers, controlling molecule exchange and
facilitating communication. The plasma membrane, like a castle moat, is a
barrier with controlled entry points for specific elements to move in and out
of the enclosed space.
4. Transporting solutes
a. The plasma membrane actively transports essential molecules like sugars
and amino acids while also establishing critical ionic gradients, which are
particularly vital for nerve and muscle cells.
5. Responding to external stimuli
a. The plasma membrane is essential for a cell's response to external signals via
signal transduction. Membranes contain receptors for interacting with
molecules and stimuli, and different cell types have unique receptors for
diverse cues. When these receptors encounter external stimuli, they trigger
signals that activate or inhibit internal processes.
6. Intercellular interaction
a. The plasma membrane, situated at a cell's outer edge, plays a vital role in
mediating interactions between cells in multicellular organisms. It enables cell
recognition, signaling, adhesion, material exchange, and information
transfer. Membrane proteins also assist in linking extracellular substances
to the intracellular cytoskeleton.
7. Energy transduction
a. Membranes are crucial for converting energy, like sunlight into chemical energy
in photosynthesis, and for transferring chemical energy from carbohydrates and
fats to ATP. These processes occur within the membranes of eukaryotic cell
structures like chloroplasts and mitochondria.
[SHANE] LIPID COMPOSITION OF MEMBRANES NATURE
Membranes are lipid-protein assemblies in which the components are held together in a thin
sheet by noncovalent bonds. The ratio of lipid to protein in a membrane varies, depending on
the type of cellular membrane, the type of organism, and the type of cell. These differences can
be correlated with the basic function of these membranes.
MEMBRANE LIPIDS
Membranes contain a wide diversity of lipids, all of which are amphipathic, that is, they contain
both hydrophilic and hydrophobic regions.
THREE MAIN TYPES OF MEMBRANE LIPIDS
1. PHOSPHOGLYCERIDES
- Most membrane lipids contain a phosphate group, which makes them phospholipids.
And because most of these membrane phospholipids are built on a glycerol backbone,
they are called phosphoglycerides.
- The membrane of glycerides are diglycerides, meaning they only two hydroxyl groups of
the glycerol are esterified to fatty acids
- Most phosphoglycerides have additional groups attached to them.
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If the additional group is choline, then it will form phosphatidylcholine.
If the additional group is ethanolamine, then it will form phosphatidylethanolamine.
If the additional group is serine, then it will form phosphatidylserine.
If the additional group is inositol, then it will form phosphatidylinositol.
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Each of these groups is small and hydrophilic, and together with the negatively charged
phosphate to which it is attached, forms a highly water-soluble domain at one end of the
molecule, called the head group or hydrophilic head.
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In contrast, fatty acyl chains are hydrophobic.
There are three types of fatty acid membrane:
Fully saturated - without double bonds
Monounsaturated - with one double bonds
Polyunsaturated - with more than one double bonds
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To summarize the composition of phosphoglycerides, phosphoglycerides contain one
saturated and one unsaturated fatty acyl chain. With fatty acid chains (hydrophobic) at
one end of the molecule and a polar (hydrophilic) head group at the other end, all the
phosphoglycerides exhibit a distinct amphipathic character.
2. SPHINGOLIPIDS
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Sphingolipids are derivatives of sphingosine, an amino alcohol that contains a long
hydrocarbon chain.
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Most sphingolipids have additional groups esterified to their terminal alcohol:
If the additional group is phosphorylcholine, then the molecule will be sphingomyelin.
If the additional group is carbohydrate, then the molecule will be glycolipid.
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There are two types of glycolipid:
If the carbohydrate is simple sugar, then the glycolipid is called cerebroside.
If the carbohydrate is a small cluster of sugars that includes sialic acid, then the
glycolipid is called ganglioside.
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Some of the functions of sphingolipids are they participate in tissue development,
cell recognition and adhesion, and they also act as receptors for toxins.
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To summarize, since all sphingolipids have two long, hydrophobic hydrocarbon chains at
one end, and a hydrophilic region at the other, they are also amphipathic and basically
similar in overall structure to the phosphoglycerides. The only difference is that the
fatty acyl chains of sphingolipids tend to be longer and more highly saturated.
3. CHOLESTEROL
- Cholesterol is a carbon compound that has a unique structure. It has a hydrocarbon tail,
a central sterol nucleus composed of four hydrocarbon rings and one hydroxyl group.
- The hydrophobic rings of cholesterol, which are flat and rigid , interact with the
hydrophobic tails of phospholipids. This stabilizes them and makes them more rigid as
well. That is the reason why cell membranes become less permeable to small
molecules.
- Cholesterol is essential, especially for regulating membrane fluidity in changing
temperatures.
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They act as a buffer:
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When the temperature is too high, cholesterol stabilizes the cell membrane and raises
its melting point.
When the temperature is too low, cholesterol raises the membrane fluidity to prevent
the membrane lipids from packing close together.
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THE NATURE AND IMPORTANCE OF THE LIPID BILAYER
- Each type of cellular membrane has its own characteristic lipid composition, differing
from one another in the types of lipids, the nature of the head groups, and the particular
species of fatty acyl chains.
- The lipids of a membrane are more than simple structural elements, they can have
important effects on the biological properties of a membrane.
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Some of the important effects of lipids on the biological properties of a membrane:
They can determine the physical state of the membrane.
They can influence the activity of particular membrane proteins.
They provide the precursors for highly active chemical messengers that regulate cellular
functions.
4. They make the membrane deformable.
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Lipid bilayer has the ability to self-assemble, which can be demonstrated during
experimentation.
For example, when a small amount of phosphatidylcholine is dispersed in an aqueous
solution, the phospholipid molecules assemble spontaneously to form the walls of
fluid-filled spherical vesicles, called liposomes.
Liposomes as used in medical therapies:
Liposomes have been developed as vehicles to deliver drugs or DNA molecules
within the body.
The drugs or DNA can be linked to the wall of the liposomes or contained at high
concentration within its lumen.
The walls of the liposomes are constructed to contain specific proteins that allow the
liposomes to bind selectively to the surfaces of the particular target cells where the drug
or DNA is intended to go.
Caelyx is an example of liposomes, it contains the chemotherapy drug doxorubicin.
Caelyx is now an accepted therapy for treatment of metastatic breast cancer.
THE ASYMMETRY OF MEMBRANE LIPIDS
- The lipid bilayer consists of two distinct leaflets that have a distinctly different lipid
composition.
- The outer leaflet has high concentration of phosphatidylcholine and low concentration of
phosphatidylethanolamine and phosphatidylserine.
- We can conclude that lipid bilayer is indeed composed of two independent monolayers
that have different physical and chemical properties.
The asymmetric distribution of phospholipids in the plasma membrane of human
erythrocytes
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Different classes of lipids:
The glycolipids of plasma membranes, which are concentrated in the outer leaflet
where they often serve as receptors for extracellular ligands.
The phosphatidylethanolamine, which is concentrated in the inner leaflet, tends to
promote the curvature of the membrane.
The phosphatidylserine, which is concentrated in the inner leaflet, has a negative
charge which makes it a candidate for binding positively charged lysine and
arginine residues.
The phosphatidylinositol, which is also concentrated in the inner leaflet of the lipid
bilayer, converts the lipid into a phosphoinositide.
Phosphoinositide transfers the stimuli from the plasma membrane to the cytoplasm and
they also recruit the proteins to the cytosolic face of the plasma membrane.
[HANNA VIANNEY] MEMBRANE CARBOHYDRATES
The plasma membranes of eukaryotic cells also contain carbohydrates. Membrane
carbohydrates are always found on the exterior surface of cells. Depending on the species and
cell type, the carbohydrate content of the plasma membrane ranges between 2 and 10 percent
by weight. More than 90 percent of the membrane’s carbohydrate is covalently linked to proteins
to form glycoproteins; the remaining carbohydrate is covalently linked to lipids to form
glycolipids.
A carbohydrate chain or glycan is another name given to glycolipids and
glycoproteins. Carbohydrate chains are found in the members of every living cell. These
carbohydrate chains may consist of 2–60 monosaccharide units and can be either
straight or branched.
Function
The main purpose of carbohydrate chains is cell-to-cell recognition. The primary
function of these chains is to recognize harmful cells (cell-cell recognition). Along with
peripheral proteins, carbohydrates form specialized sites on the cell surface that allow
cells to recognize each other. This recognition function is very important to cells, as it
allows the immune system to differentiate between body cells (called “self”) and foreign
cells or tissues (called “non-self”). Similar types of glycoproteins and glycolipids are
found on the surfaces of viruses and may change frequently, preventing immune cells
from recognizing and attacking them.
Example:
Blood‐group antigens. Whether a person has type A, B, AB, or O blood is determined
by a short chain of sugars covalently attached to membrane lipids and proteins of the
red blood cell membrane.
MEMBRANE PROTEINS
Membrane proteins are those proteins that are either a part of or interact with
biological membranes. Depending on the cell type and the particular organelle within
that cell, a membrane may contain hundreds of different proteins. It can be composed of
up to 75% protein, around ⅓ of human proteins and most cell membranes have 50% or
less protein.
Types of proteins in cell membranes
Integral protein - appear anywhere in the cell membrane and there are quite few of
these in the entire cell. Transmembrane proteins are firmly inserted into the
phospholipid bilayer.
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Channel protein - Allow things to pass through the cell membrane. There
is a channel or hole inside the cell and let things pass through.
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Carrier protein - carries substances into the cell. If there are molecules
outside the cell and the cell needs the molecules, the carrier protein protects this
substance so they can enter the cell safely or vice versa.
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Glycoprotein - chain of sugars attached to a protein, can be on integral or
peripheral proteins.
Peripheral proteins - appear on the surface of the membrane and sometimes it can be
slightly into the membrane. It can also rest on top of integral proteins. It is called
peripheral because it is on the outside of the membrane. However, peripheral proteins
can exist in the cell membrane.
Lipid-bound protein - rare type of protein. Proteins are there to interact with the
outside environment, and lipid-bound proteins are stuck on the interior of the cell
membrane. This protein enhances the aqueous solubility of lipids and facilitates their
transport between tissues and within tissue cells.
Function
Membrane proteins can serve a variety of key functions:
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Junctions – Serve to connect and join two cells together
Enzymes – Fixing to membranes localizes metabolic pathways
Transport – Responsible for facilitated diffusion and active transport
Recognition – May function as markers for cellular identification
Anchorage – Attachment points for cytoskeleton and extracellular matrix
Transduction – Function as receptors for peptide hormones
[STEVEN] STRUCTURE AND PROPERTIES OF INTEGRAL MEMBRANE PROTEINS
Integral Membrane Proteins
● Also called transmembrane proteins or intrinsic proteins
● Spans across the phospholipid bilayer
● Permanently embedded in the lipid bilayer
● Serves as channels through which molecules move across the cell membrane
● Amount and types of amino acids vary between different integral proteins
Typology of Transmembrane Proteins
● Based on the Structure
○ α-helix integral membrane proteins:
These are single long strand of amino
acids with intramolecular hydrogen
bonding within the polypeptide chain,
creating a spiral or right-handed coiled
rod-like structure
○ α-helix bundle (helical bundle): These
are several alpha helices packed
together in a parallel or antiparallel
orientation
○ β-barrel integral membrane proteins: These consist of several beta-sheets
(two or more hydrogen-bonded parallel or antiparallel beta strands with amino
acids in an extended conformation, i.e., linear or sheet-like structure) rolled up
forming a barrel-like structure. It is formed by a closed beta sheet around a
central pore. Beta barrels consist usually of an even number of beta strands
(between 8 and 24), and are found only in bacterial outer membranes,
mitochondria and chloroplasts. (This is one evidence of endosymbiotic theory:
eukaryotic cells acquired these organelles through the ingestion of prokaryotes)
General Characteristic:
The surface of the alpha helix that interacts with
the hydrophobic tails of the phospholipid bilayer
is also hydrophobic. It contains hydrophobic
nonpolar amino acids that help prevent
repulsion and keep the integral protein in place.
However, the internal part of the helix and the
region that branches out to the cytosol and
outside the cell contain hydrophilic polar amino
acids. This structure favors the passage of water
molecules and other ions. Likewise, the
beta-barrel has a hydrophobic outer layer that
interacts with the hydrophobic part of the lipid
bilayer while its hydrophilic inside forms an
aqueous pore that supports transport of water
molecules and other ions.
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Based on Number of Passes in the Lipid
Bilayer
○ Single-pass membrane proteins
(Bitopic): These are also called
single-spanning proteins which span the
lipid bilayer only once, from one end to
another.
○ Multipass membrane proteins
(Polytopic): These are transmembrane
proteins that traverse the lipid bilayer
multiple times like the helix bundle and β-barrel membrane proteins.
Additional Characteristic:
Most transmembranes are glycosylated: Most integral membrane proteins undergo
glycosylation, the attachment of sugar molecules to proteins by glycosidic linkage. The
transmembrane proteins with attached carbohydrates are referred to as glycoproteins. They
perform vital biochemical and structural functions. They enable cells to recognize another cell as
familiar or foreign, which is called cell-cell recognition. They also help cells attach to and bind
other cells, which is called cell adhesion. Furthermore, they also act as receptors – when a
specific molecule binds to its receptor, it triggers a chain reaction inside the cell which will
generate a desired effect.
Transport Membrane Proteins
Transport proteins function in both active and passive transport to move molecules across the
plasma membrane. The two major classes of membrane transport proteins are the carrier
proteins and channel proteins.
Carrier proteins (also called carriers, permeases, or transporters) bind the specific solute to be
transported and undergo a series of conformational changes to transfer the bound solute across
the membrane. Channel proteins, in contrast, interact with the solute to be transported much
weaker. They form aqueous pores that extend across the lipid bilayer; when these pores are
open, they allow specific solutes (usually inorganic ions of appropriate size and charge) to pass
through them and thereby cross the membrane.
Channel and carrier proteins transport material at different rates. In general, channel proteins
transport molecules much more quickly than do carrier proteins. This is because channel
proteins are simple tunnels; unlike carrier proteins, they don't need to change shape and “reset”
each time they move a molecule.
Carrier proteins
Channel proteins
Carrier proteins are essential proteins that
carry chemicals across the membrane in both
directions, down and up the concentration
gradient.
Channel proteins are proteins that can
generate hydrophilic holes in cell
membranes, allowing molecules to go down a
concentration gradient.
Carrier proteins transport substances both
uphill and downhill the concentration gradient.
Substances are transported down a
concentration gradient by channel proteins.
Carrier proteins are proteins that bind to
molecules or ions on one side of the
membrane and release them on the other.
Channel proteins create holes/pores that
penetrate the membrane, enabling target
molecules or ions to flow through via diffusion
without interfering with one another.
Uniporters, symporters, antiporters, and other
transport carrier proteins are classified
according to their characteristics.
The channel proteins are
potential-dependent, ligand-dependent,
mechanically dependent, and so on,
depending on the component that activates or
inactivates them.
Carrier proteins require energy only to
transport molecules in the opposite direction
of the concentration gradient.
Channel proteins do not use energy.
Sodium-potassium pump, glucose-sodium
cotransport, valinomycin, and other carrier
proteins are examples.
Chloride, potassium, calcium, sodium ion
channels, aquaporins, and other channel
proteins are examples.
Methods for Solubilization of Transmembrane Proteins
In order to study the structure and functions of integral membrane proteins these proteins must
be extracted and isolated in soluble form. However, membrane proteins, unlike soluble proteins,
are difficult to analyze in their native environment due to their insertion in the lipid membrane.
The hydrophobic domains won’t interact with water and it tends to aggregate when taken out of
the lipid bilayer resulting in sticky precipitation of unfolded proteins.
There are three possible methods for solubilization of transmembrane proteins:
● Using Detergent: Like membrane lipids, detergents are amphipathic, being composed
of a polar end and a nonpolar hydrocarbon chain. As a consequence of their structure,
detergents can substitute for phospholipids in stabilizing integral proteins while rendering
them soluble in aqueous solution. Once the proteins have been solubilized by the
detergent, various analyses can be carried out to determine the protein’s amino acid
composition, molecular mass, amino acid sequence, and so forth.
● Using Lipopeptides: Lipopeptides have a lipid-like structure attached to a peptide. The
lipid molecules, which are hydrophobic, will interact with the hydrophobic domain of the
transmembrane proteins. However, since lipids are hydrophobic, they will also still not
interact with water, thus, the proteins in the peptide chain will serve as the hydrophilic
region. In other words, the lipopeptide serves as the detergent with amphipathic
molecules, the hydrophobic lipid and hydrophilic proteins/peptide.
● Using Nanodiscs: Nanodiscs are small disc-shaped structures consisting of two main
components: phospholipids that are either of artificial origin or from the cell membrane
and; the stabilizing belt that holds the phospholipids together. Surfaces of membrane
proteins in the hydrophobic core of the lipid bilayer are also hydrophobic, whereas
surface areas in contact with the aqueous membrane environment are as hydrophilic as
the surfaces of ordinary soluble proteins. The presence of extensive hydrophobic and
hydrophilic surfaces on the same molecule is characteristic of membrane proteins. As a
result, membrane proteins are not soluble in standard aqueous buffers without a
solubilizing agent. Therefore, nanodiscs are used to solubilize them by mimicking the
amphipathic environment of a lipid bilayer whilst maintaining the structure of the
membrane protein in a physiologically relevant state.
[RICHMOND] MEMBRANE LIPIDS AND MEMBRANE FLUIDITY
Phospholipids are compound lipids, consisting of phosphoric acids, nitrogen base, alcohol and
fatty acids. These compound lipids are major components of the cell membrane and also
provide a fluid character to the membranes. In cell membranes, these phospholipids have a
hydrophilic head and a hydrophobic tail, which forms the inside of the bilayer.
In 1972, S. Jonathan Singer and Garth Nicolson developed the fluid-mosaic model of
membrane structure. According to this model, a membrane is a double layer (bilayer) of proteins
and phospholipids and is fluid rather than solid. The phospholipid bilayer forms a fluid “sea” in
which specific proteins float like icebergs. Being fluid, the membrane is in a constant state of
flux—shifting and changing, while retaining its uniform structure. This model describes the
structure of the plasma membrane as a mosaic of components — including phospholipids,
cholesterol and proteins that gives the membrane a fluid character.
These important points in the fluid mosaic model are also the factors that lead to membrane
fluidity.
MEMBRANE LIPIDS IMPORTANCE
What is important about the structure of a phospholipid membrane? First, it is fluid. This
allows cells to change shape, permitting growth and movement. The fluidity of the membrane is
regulated by the types of phospholipids and the presence of cholesterol. Second, the
phospholipid membrane is selectively permeable.
The ability of a molecule to pass through the membrane depends on its polarity and to
some extent its size. Many non-polar molecules such as oxygen, carbon dioxide, and small
hydrocarbons can flow easily through cell membranes. This feature of membranes is very
important because hemoglobin, the protein that carries oxygen in our blood, is contained within
red blood cells. Oxygen must be able to freely cross the membrane so that hemoglobin can get
fully loaded with oxygen in our lungs, and deliver it effectively to our tissues. Most polar
substances are stopped by a cell membrane, except perhaps for small polar compounds like the
one carbon alcohol, methanol. Glucose is too large to pass through the membrane unassisted
and a special transporter protein ferries it across. One type of diabetes is caused by
misregulation of the glucose transporter. This decreases the ability of glucose to enter the cell
and results in high blood glucose levels. Charged ions, such as sodium (Na+) or potassium (K+)
ions seldom go through a membrane, consequently they also need special transporter
molecules to pass through the membrane. The inability of Na+ and K+ to pass through the
membrane allows the cell to regulate the concentrations of these ions on the inside or outside of
the cell. The conduction of electrical signals in your neurons is based on the ability of cells to
control Na+ and K+ levels.
Selectively permeable membranes allow cells to keep the chemistry of the cytoplasm
different from that of the external environment. It also allows them to maintain chemically unique
conditions inside their organelles.
MEMBRANE FLUIDITY
The structure of the cell membrane is dynamic and because of its dynamic structure, proteins
and phospholipids can move around freely. The ability of molecules to move freely within the
membrane is referred to as "fluidity," which is crucial for cell function.
There are multiple factors that lead to membrane fluidity:
1. The plasma membrane is kept fluid because of its mosaic structure. The essential lipids
and proteins are separate but loosely bound molecules that are present in the
membrane. The membrane is fairly rigid and can burst if penetrated or if a cell takes in
too much water, rather than being like a balloon that can expand and contract. A very
fine needle can, however, easily penetrate a plasma membrane due to its mosaic
structure; the membrane will flow and self-seal when the needle is removed.
2. The characteristics of the phospholipids themselves are the second factor contributing to
fluidity. The phospholipid tails' fatty acids are in their saturated form, which lacks the
presence of double bonds between nearby carbon atoms and is saturated with bound
hydrogen atoms. As a result, the tails are mostly straight. Unsaturated fatty acids, in
contrast, do not contain the greatest amount of hydrogen atoms, but they do contain
some double bonds between adjacent carbon atoms; a double bond causes the string of
carbons to bend by about 30 degrees. Therefore, if straight-tailed saturated fatty acids
are compressed by lowering temperatures, they press in on each other to create a dense
and reasonably rigid membrane. When unsaturated fatty acids are compressed, the
"kinks" in their tails push nearby phospholipid molecules apart, preserving some distance
between them. At temperatures where membranes with saturated fatty acid tails in their
phospholipids would "freeze" or "solidify," this "elbow room" aids in maintaining fluidity in
the membrane. In a cold environment, the relative fluidity of the membrane is crucial.
Membranes made primarily of saturated fatty acids are often compressed in a cold
environment, becoming less fluid and more prone to rupturing. By altering the proportion
of unsaturated fatty acids in their membranes in response to the drop in temperature,
many organisms, including fish, are able to adapt to cold environments.
3. In animals, cholesterol is the third factor that maintains the fluidity of the membrane. It
resides in the membrane next to the phospholipids and can reduce the effects of
temperature on the membrane. As a result, cholesterol acts as a buffer, preventing both
the excessive increase in fluidity caused by higher temperatures and the inhibition of
fluidity caused by lower temperatures. The range of temperatures in which the
membrane is appropriately fluid and, as a result, functional is expanded in both
directions by cholesterol. Other jobs for cholesterol include forming lipid rafts from
collections of transmembrane proteins.
[JAMAICA] THE DYNAMIC NATURE OF THE PLASMA MEMBRANE
This part discusses the dynamic nature of the plasma membrane, which is the outer
layer of cells. It explains that the membrane is made up of a lipid bilayer, and these lipids can
move around within the same layer quite easily. This movement can be observed under a
microscope. It also mentions that while lipids can move within one layer quickly, it takes a longer
time for them to move to the other layer. This is because moving through the membrane's
internal structure is difficult. However, cells have enzymes called flippases that help move
certain lipids from one layer to the other, which is important for maintaining the membrane's
structure.
Furthermore, this part highlights that the physical state of these lipids affects how
proteins within the membrane can move. The ability of proteins to move within the membrane
was a key concept in the development of the fluid-mosaic model, which describes the structure
of cell membranes. This part also hints at various ways scientists have discovered the dynamic
properties of these membrane proteins.
The Diffusion of Membrane Proteins after Cell Fusion
This part discusses a technique called cell fusion, where two different types of cells or
cells from different species are combined to form a single cell with a shared interior and one
continuous outer membrane.
To achieve cell fusion, scientists make the cell surfaces "sticky" so that their membranes
stick together. This can be done using methods like inactivated viruses, a compound called
polyethylene glycol, or mild electric shocks. Cell fusion is an essential tool in cell biology and is
used for various purposes, including preparing specific antibodies.
Restrictions on Protein and Lipid Mobility
This part discusses techniques used by researchers to understand how molecules move within
the cell's membranes.
Fluorescence Recovery After Photobleaching (FRAP): This technique involves labeling
integral membrane components with a fluorescent dye.
Single-Particle Tracking (SPT): This method tracks individual membrane protein molecules
labeled with fluorescent tags. The results vary depending on the protein studied:
● Some proteins move randomly within the membrane, albeit at rates slower than
expected.
● Some proteins remain immobilized and do not move.
● Others show directed movement, moving purposefully toward specific parts of the cell.
● Most proteins exhibit random, Brownian movement, but their long-range diffusion is
slower due to barriers within the membrane.
In essence, these techniques help researchers understand how proteins and other molecules
move within cell membranes, shedding light on their mobility and behavior in different cellular
contexts.
Control of Membrane Protein Mobility
This part discusses how the mobility of proteins within the cell's plasma membrane is controlled
and influenced.
Crowded Membranes: Some cell membranes have many proteins packed closely together.
This crowding can hinder the random movement of individual proteins because they can bump
into their neighbors.
Influence from Beneath the Membrane: The most significant influences on the movement of
integral membrane proteins come from just beneath the membrane on its inner, cytoplasmic
side. Many cell membranes have a network of proteins called a "membrane skeleton" on this
side. Some integral proteins are anchored to this skeleton or constrained by it, limiting their
mobility.
Using Optical Tweezers: Scientists use a technique called optical tweezers, which relies on
focused laser beams, to trap and move integral proteins within the membrane. They found that
these proteins can be dragged for a short distance before encountering a barrier that makes
them spring back. This suggests the presence of elastic structures acting as barriers.
Genetic Modification: Researchers modify cells genetically to produce altered membrane
proteins. When the cytoplasmic portion of integral proteins is genetically deleted, these proteins
can move longer distances, indicating that barriers exist on the inner side of the membrane.
These barriers create compartments within the membrane, and proteins can move between
these compartments through breaks in the barriers. This organization may facilitate protein
interactions.
Impact of Extracellular Materials: Proteins that have portions projecting into the extracellular
space typically move more slowly through the membrane. This is because extracellular
materials can entangle these external portions of the protein, slowing down their movement.
The movement of proteins within the cell's membrane is not random. It's influenced by factors
like protein crowding, the presence of a membrane skeleton, genetic modifications, and
interactions with extracellular materials. These factors help organize and control the mobility of
proteins in the membrane.
Membrane Lipid Mobility
This part discusses the movement of lipids, specifically phospholipids, within the cell's lipid
bilayer.
Size Difference: Proteins are large molecules, so it's understandable that their movement
within the lipid bilayer is limited. On the other hand, phospholipids are much smaller and make
up the structure of the lipid bilayer. You might expect them to move freely, but studies have
shown that their diffusion is also restricted.
Phospholipid Movement: When researchers tag individual phospholipid molecules in the cell's
membrane and observe them under high-speed cameras, they notice that the phospholipids are
confined to small areas for short periods and then move to adjacent areas. It's as if they hop
from one confined region to another.
Fences in the Membrane: These confined areas are likened to compartments surrounded by
"fences." Treatment of the membrane with certain agents that disrupt the underlying membrane
skeleton can remove some of these fences, allowing phospholipids to move more freely.
Membrane Skeleton's Role: The membrane skeleton is situated beneath the lipid bilayer.
Researchers believe that the fences restricting phospholipid movement are made up of rows of
integral membrane proteins whose inner parts are connected to the membrane skeleton. This
arrangement is similar to how picket fences in the ground confine animals like horses or cows.
While phospholipids are small, their movement within the cell's membrane is not entirely free,
and the presence of integral membrane proteins connected to the membrane skeleton appears
to play a role in this confinement.
Membrane Domains and Cell Polarity
This part discusses how cell membranes can vary in terms of protein composition and mobility,
especially in cells with different functions on various surfaces.
Cell Surface Variations: While many studies focus on the uniform plasma membrane of cells
cultured in a dish, most membranes in living organisms exhibit differences in the types of
proteins and how they move. This is particularly true in cells with distinct functions on different
surfaces.
Examples of Variations: For instance, in cells like intestinal lining cells or kidney tubule cells,
different surfaces of the cell have different functions. The top surface (apical plasma membrane)
may have different enzymes than the sides (lateral plasma membrane) that interact with
neighboring cells or the bottom (basal membrane) that attaches to the underlying structure
(basement membrane).
Specialized Membrane Regions: In other examples, certain receptors concentrated in specific
regions of the plasma membrane facilitate specialized functions. For instance, receptors for
neurotransmitters are found in specific areas within synapses, and receptors for low-density
lipoproteins are concentrated in patches of the plasma membrane specialized for their
internalization.
Sperm Cell Complexity: Sperm cells are highly specialized, with distinct regions for different
functions like the head, midpiece, and tail. Despite these divisions, the sperm cell's outer
membrane is continuous but consists of different localized domains. These domains can be
revealed through various techniques, showing unique patterns when treated with specific
antibodies targeting certain protein antigens.
Cell membranes are not uniform; they have specialized regions with different protein
compositions and functions. This variation helps cells perform their specific roles efficiently.
REVIEW QUESTIONS
1. Techniques to Measure Protein Diffusion Rates:
Fluorescence Recovery After Photobleaching (FRAP): This technique involves labeling
specific membrane proteins with a fluorescent dye. A laser beam is then used to bleach a small
area of fluorescence in the membrane. If the labeled proteins are mobile, they gradually
reappear in the bleached area. The rate at which fluorescence returns provides a measure of
the protein's diffusion rate within the membrane.
Single-Particle Tracking (SPT): In SPT, individual membrane protein molecules are labeled
with fluorescent tags. Specialized microscopy, such as Total Internal Reflection Fluorescence
(TIRF), is used to observe these labeled molecules at the cell's surface. This allows researchers
to track the movement of individual protein molecules and determine their diffusion rates.
2. Figure 4.28 describes various patterns of movement exhibited by integral membrane
proteins within cell membranes. Let's compare and contrast these patterns:
Protein A - Random Diffusion:
Pattern: Capable of random diffusion throughout the membrane.
Limitation: Movement rate may be limited.
Protein B - Immobilized:
Pattern: Immobilized due to its interaction with the underlying membrane skeleton.
Protein C - Directed Movement:
Pattern: Moved in a specific direction due to interaction with a motor protein on the cytoplasmic
surface
Protein D - Restricted by Other Proteins:
Pattern: Movement is restricted by the presence of other integral proteins in the membrane.
Protein E - Movement with Hopping:
Pattern: Movement is restricted by fences formed by proteins in the membrane skeleton.
Additional Detail: It can hop into adjacent compartments through temporary openings in these
"fences."
Protein F - Restrained by Extracellular Materials:
Pattern: Movement is restrained by extracellular materials outside the cell.
Comparison:
Proteins A and E: Both can experience some level of restricted movement. Protein A can
diffuse randomly but might be slower, while Protein E is confined within compartments but can
hop between them through openings.
Proteins B and F: Both are restricted in their movement but by different factors. Protein B is
immobilized due to interactions with the membrane skeleton, while Protein F is restrained by
extracellular materials.
Proteins C and D: Both experience directed movement or restrictions within the membrane, but
for different reasons. Protein C is moved by motor proteins, while Protein D is restricted by other
integral proteins.
Contrast:
Protein A vs. Protein B: Protein A can move randomly but may have some limitations in
speed, while Protein B is completely immobilized.
Protein C vs. Protein D: Protein C undergoes directed movement due to interactions with
motor proteins, while Protein D experiences movement restrictions because of the presence of
other integral proteins.
Protein E vs. Protein F: Protein E is confined by fences formed by membrane skeleton
proteins but can hop between compartments. In contrast, Protein F is restrained by extracellular
materials outside the cell.
Integral membrane proteins can exhibit diverse patterns of mobility within cell membranes,
influenced by their interactions with various cellular components and the extracellular
environment. These patterns range from free diffusion to complete immobilization, directed
movement, or confinement with occasional hopping between compartments.
3. Comparison of Lipid Lateral Diffusion with Flip-Flop:
Lateral Diffusion: Lipids within the lipid bilayer can move laterally within the same leaflet with
relative ease. Their lateral diffusion rate is relatively fast because they can move within the
same layer of the membrane, which is composed of hydrophobic tails that allow for relatively
unhindered movement.
Flip-Flop: Flip-flop refers to the process of a lipid molecule moving from one leaflet of the lipid
bilayer to the other, effectively "flipping" across the membrane. This process is much slower
than lateral diffusion because it involves the hydrophilic head group of the lipid passing through
the hydrophobic interior of the membrane. This is thermodynamically unfavorable and requires
specific enzymes known as flippases to facilitate the process.
Reason for the Difference: The main reason for the difference in rates between lateral
diffusion and flip-flop is the barrier posed by the hydrophobic core of the lipid bilayer. Lateral
diffusion occurs within the same leaflet and primarily involves interactions between the lipid tails,
which are hydrophobic and allow for relatively free movement.
In contrast, flip-flop requires the hydrophilic head group of the lipid to traverse the hydrophobic
core, which is energetically unfavorable due to the mismatch in polarity. This process is slowed
down significantly and is not thermodynamically favored. To overcome this barrier, cells have
specialized enzymes (flippases) that actively facilitate flip-flop to maintain lipid asymmetry
between the leaflets of the membrane.
SUMMARY OF EACH FIGURES:
[JHON REY]
RED BLOOD CELL AN EXAMPLE OF PLASMA MEMBRANE STRUCTURE
The plasma membrane of erythrocytes is a classic example of a plasma membrane
structure because of their:
○
○
○
○
○
○
Phospholipid bilayer- in the bilayer, the hydrophilic heads face outward,
interacting with the aqueous environment, while the hydrophobic tails are
shielded inside, away from water.
Integral proteins- embedded within the lipid bilayer; they serve as transporters.
Peripheral proteins- plays a role in cell signaling, cell adhesion, and membrane
stability.
Glycoproteins and glycolipids- essential for cell recognition and interaction
with other cells.
Selective permeability- erythrocyte’s plasma membrane is selectively
permeable.
Flexibility- erythrocyte membrane is flexible and elastic which allows it to
deform and squeeze through capillaries in the circulatory system without
rupturing.
○
Lack of nucleus and organelles- erythrocytes lack nucleus, and in most
mammals, erythrocytes do not contain any organelles.
Why is the plasma membrane of erythrocytes a good model for membrane structure
studies?
●
●
●
●
They lack most of the complex membrane-bound organelles and they have a simple
structure.
They are abundant.
They lack a nucleus.
They are stable and robust.
To summarize, a red blood cell's plasma membrane exemplifies the fundamental
structure of cell membranes found in all living cells. It is made up of a phospholipid bilayer with
proteins embedded in it, forming a selective barrier that controls the movement of molecules
and ions while maintaining the cell's integrity and functionality. This structure is critical for red
blood cell survival and function as they circulate through the body, delivering oxygen to tissues
and removing carbon dioxide.
SOLUTE MOVEMENT ACROSS CELL MEMBRANES
Solute movement across cell membranes is a fundamental biological process that is essential
for cell function and homeostasis. Understanding how solutes cross cell membranes is critical
for many biological and physiological processes.
1. Passive Transport:
a. Diffusion:
Diffusion is one of the primary mechanisms for solute movement across
cell membranes. Diffusion is the spontaneous movement of solute molecules
from a high concentration area to a low concentration area. This movement
occurs as a result of solute molecules spreading out to achieve equilibrium.
Because of factors such as size, charge, and lipid solubility, cell membranes are
selectively permeable, allowing some solutes to pass through while blocking
others. Small, nonpolar molecules (such as oxygen and carbon dioxide) can
freely diffuse through the lipid bilayer, whereas larger or polar molecules may
necessitate the assistance of transport proteins.
b. Facilitated Diffusion:
Because of their size or charge, some solutes cannot easily diffuse
through the lipid bilayer. In such cases, cells use specialised proteins known as
transporters or channels to help them move. Because solutes move from high to
low concentration, facilitated diffusion is still a passive process, but it requires the
assistance of specific proteins. Glucose transporters, for example, aid in the entry
of glucose molecules into cells by facilitating their diffusion across the membrane.
2. Active Transport:
a. Primary Active Transport:
Active transport is a process that requires energy input, typically in the
form of ATP (adenosine triphosphate). In primary active transport, specific
membrane proteins known as pumps actively move solutes against their
concentration gradient, from an area of lower concentration to an area of higher
concentration. A classic example is the sodium-potassium pump, which is found
in many cell types. It pumps sodium ions out of the cell and potassium ions into it
in order to maintain ion gradients, which are required for a variety of cellular
functions.
b. Secondary Active Transport (Cotransport):
Secondary active transport, also known as cotransport, uses energy from
primary active transport to move solutes indirectly. It involves the coupling of the
movement of one solute against its gradient to the movement of another solute
down its gradient. In the intestinal lining, for example, the sodium-glucose
cotransporter (SGLT) couples the movement of glucose against its concentration
gradient to the movement of sodium ions with their concentration gradient.
3. Vesicular Transport:
a. Endocytosis:
Some large or macromolecular solutes cannot be transported across the
cell membrane via diffusion or active transport. In such cases, cells use
endocytosis, a vesicular transport process, to engulf and internalize solutes. This
includes processes such as phagocytosis (the engulfment of solid particles) and
pinocytosis (the engulfment of liquid droplets), both of which are essential for
nutrient uptake and immune defense.
b. Exocytosis:
Cells, on the other hand, use exocytosis to expel solutes or substances
contained in vesicles from the cell. This process is required for the release of
neurotransmitters, hormones, and other cellular products.
In conclusion, solute movement across cell membranes is a complex and highly
regulated process involving a variety of mechanisms. Active transport requires energy
expenditure to move solutes against concentration gradients, whereas passive transport relies
on diffusion and facilitated diffusion. The bulk movement of solutes via endocytosis and
exocytosis is referred to as vesicular transport. These processes work together to ensure that
cells can keep their internal environment stable, regulate ion concentrations, and transport
essential molecules for various physiological functions.
[TANTAN] DIFFUSION THROUGH THE LIPID BILAYER
The plasma membrane is an essential component of cells, acting as a gatekeeper that controls
the entry and exit of substances. Therefore, Understanding the mechanisms by which solutes
traverse on this barrier is a fundamental to comprehending cellular physiology.
One of the primary mechanisms by which solutes traverse the plasma membrane is simple
diffusion through the lipid bilayer. This process is characterized by its energy-independence.
Meaning, It allows solutes to move down an electrochemical gradient, dissipating the free
energy stored within the gradient.
On the other hand, The plasma membrane exhibits selective permeability, meaning it allows
some solutes to pass freely while restricting the passage of others. This selectivity is crucial for
maintaining cellular homeostasis.
The permeability is determined by the nature of the solute:
•
Small Inorganic Solutes:
Small inorganic solutes, including oxygen (O2), carbon dioxide (CO2), and water (H2O), readily
penetrate the lipid bilayer. Their molecular size and lipophilic properties enable them to traverse
the membrane without the need for specialized transporters.
•
Solutes with High Lipid Solubility:
Similarly, solutes with high lipid solubility can efficiently traverse the lipid bilayer due to their
compatibility with the hydrophobic environment of the membrane.
•
Ions and Polar Organic Solutes:
In contrast, ions and polar organic solutes such as sugars and amino acids face a different
challenge since their hydrophilic nature makes it difficult for them to pass through the lipid
bilayer. As a result, these solutes require special transporters to facilitate their entry into or exit
from the cell.
Diffusion of Substances through Membranes
Two qualifications must be met before a nonelectrolyte can diffuse passively across a plasma
membrane:
A.
The substance must be present at higher concentration on one side of the membrane
than the other, and
B.
The membrane must be permeable to the substance. Specifically, a membrane may be
permeable to a given solute either (1) because that solute can pass directly through the lipid
bilayer, or (2) because that solute can traverse an aqueous pore that spans the membrane.
There are selective consideration/factors leading to diffusion.
(1)
Concentration gradient: the concentration difference of a solute on either side of the
bilayer determines the direction and rate of diffusion. Movement occurs from an area of higher
concentration to an area of lower concentration (down the concentration gradient).
(2)
Lipid solubility: lipophilic or hydrophobic molecules diffuse more readily through the
bilayer than hydrophilic molecules.
One of the measurements used to determine the rate of solubility of specific substance is its
polarity. Measure of polarity is utilized through partition coefficient, which is the ratio of its
solubility in a nonpolar solvent, such as octanol, to that in water under conditions where the
nonpolar solvent and water are mixed together. In other words, it is the ratio of the concentration
of a substance in one medium or phase (C1) to the concentration in a second phase (C2) when
the two concentrations are at equilibrium. It is a measure of the lipophilicity of a drug/chemical
and an indication of its ability to cross the cell membrane. It is a concept of whether the
molecule is partitioning or not.
•
the greater the lipid solubility, the faster the penetration.
(3)
Molecular size: smaller molecules typically diffuse more rapidly than larger ones.
(4)
Temperature: higher temperatures generally increase the kinetic energy of molecules,
promoting faster diffusion.
DIFFUSION OF WATER THROUGH MEMBRANES
Water molecules move much more rapidly through a cell membrane than do dissolved ions or
small polar organic solutes, which are essentially nonpenetrating. Because of this difference in
the penetrability of water versus solutes, membranes are said to be semipermeable .
Water moves readily through a semipermeable membrane from a region of lower solute
concentration to a region of higher solute concentration. This process is called osmosis , and it
is readily demonstrated by placing a cell into a solution containing a nonpenetrating solute at a
concentration different than that present within the cell itself.
When two compartments of different solute concentration are separated by a semipermeable
membrane, the compartment of lower solute concentration, which is described as being
hypotonic (or hypoosmotic ) reative to compartment of higher solute concentration is said to be
hypertonic (or hyperosmotic).
Looking at the figure , When a cell is placed into a hypotonic solution, the cell rapidly gains
water by osmosis and swells). Conversely, a cell placed into a hypertonic solution rapidly loses
water by osmosis and shrinks. These simple observations show that a cell’s volume is controlled
by the difference between the solute concentration inside the cell and that in the extracellular
medium. The swelling and shrinking of cells in slightly hypotonic and hypertonic media are
usually only temporary events. Within a few minutes, the cells recover and return to their original
volume.
In a hypotonic medium, recovery occurs as the cells lose ions, thereby reducing their internal
osmotic pressure. In a hypertonic medium, recovery occurs as the cells gain ions from the
medium. Once the internal solute concentration (which includes a high concentration of
dissolved proteins) equals the external solute concentration, the internal and external fluids are
isotonic (or isosmotic ), and no net movement of water into or out of the cells occurs.
Osmosis is an important factor in a multitude of bodily functions. Your digestive tract, for
example, secretes several liters of fluid daily, which is reabsorbed osmotically by the cells that
line your intestine. If this fluid weren’t reabsorbed, as happens in cases of extreme diarrhea, you
would face the prospect of rapid dehydration.
THE EFFECTS OF OSMOSIS ON A PLANT CELL.
Plants utilize osmosis in different ways. Unlike animal cells, which are generally isotonic with the
medium in which they are bathed, plant cells are generally hypertonic compared to their fluid
environment. As a result, there is a tendency for water to enter the cell, causing it to develop an
internal ( turgor ) pressure that pushes against its surrounding wall as you can see on figure on
the left, letter A. Turgor pressure provides support for nonwoody plants and for the nonwoody
parts of trees, such as the leaves. If a plant cell is placed into a hypertonic medium, its volume
shrinks as the plasma membrane pulls away from the surrounding cell wall, a process called
plasmolysis like letter B. The loss of water due to plasmolysis causes plants to lose their support
and wilt.
FIGURE 2. PASSAGE OF WATER MOLECULES THROUGH AN AQUAPORIN CHANNEL.
Cell permeability to water varies among different cells, and many cells exhibit higher water
permeability than can be explained by simple lipid bilayer diffusion. Aquaporins, a family of small
integral proteins, facilitate the passive movement of water across the plasma membrane. These
proteins have a central channel with hydrophobic amino acid residues, specifically designed for
water molecules. Remarkably, each aquaporin channel can allow approximately a billion water
molecules to pass through it per second, while effectively excluding H+ ions.
Structural insights into aquaporins have been gained through X-ray crystallography and
molecular dynamics simulations. These studies reveal that aquaporin channels contain
strategically positioned positive charges (N203 and N68 residues) near their narrowest point.
These charges attract and redirect water molecules passing through the channel, disrupting
their normal hydrogen bonding pattern and preventing the transfer of protons between water
molecules.
Aquaporins are especially prominent in cells where water transport is crucial, such as kidney
tubule cells and plant root cells. The hormone vasopressin regulates water retention in the
kidney's collecting ducts by acting on one of these aquaporin proteins, AQP2. Mutations in the
aquaporin channel, like AQP2, can lead to congenital nephrogenic diabetes insipidus, a
hereditary disorder characterized by excessive urine excretion due to the kidneys' inability to
respond to vasopressin.
Explanation of Figure:
This passage presents a molecular dynamics simulation snapshot showing a stream of water
molecules (depicted as red and white spheres) moving in single file through a channel in one of
the subunits of an aquaporin molecule within a membrane. The simulation is accompanied by a
model explaining how water molecules pass through an aquaporin channel while excluding
protons.
In the model, nine water molecules are observed lined up in a single file along the channel's
wall. Each water molecule is represented as a red circular oxygen (O) atom with two associated
hydrogen atoms (H). Notably, the four water molecules at the top and bottom of the channel
have their hydrogen atoms oriented away from the center of the channel due to interactions with
the protein's carbonyl (C=O) groups. This orientation enables these water molecules to form
hydrogen bonds (depicted as dashed lines) with their neighboring water molecules.
Conversely, the single water molecule positioned at the center of the channel is oriented in a
way that prevents it from forming hydrogen bonds with other water molecules. This unique
orientation disrupts the flow of protons through the channel, illustrating how aquaporin channels
selectively allow the passage of water molecules while excluding protons.
[CHRISTINE] THE DIFFUSION OF IONS THROUGH MEMBRANES
As we go through the cell membrane which separates the interior of the cell from the outside
environment. The cell membrane can be semi-permeable, impermeable, permeable and
selectively permeable in nature because it regulates the transport of materials entering and
exiting the cell.
In 1955, Alan Hodgkin and Richard Keynes first proposed that cell membranes contain ion
channels which are the openings in the membrane that are permeable to specific ions. Ion
channels are protein molecules that span across the cell membrane allowing the passage of
ions from one side of the membrane to the other.
In late 1970s and early 1980s, direct proof of the existence of ion channels emerged through the
work of Bert Sakmann and Erwin Neher. They developed techniques to monitor the ionic current
passing through a single ion channel. Most ion channels are highly selective in allowing only
one particular type of ion to pass through the pore. As with the passive diffusion, it is a process
by which molecules diffuse from a region of higher concentration to a region of lower
concentration.
Most of the ion channels that have been identified can exist in either an open or a closed
conformation; such channels are said to be gated. Three major categories of gated channels
are distinguished:
1. VOLTAGE-GATED CHANNELS
- whose conformational state depends on the difference in ionic charge on the two
sides of the membrane
2. LIGAND-GATED CHANNELS
- whose conformational state depends on the binding of a specific molecule (the
ligand), which is usually not the solute that passes through the channel
3. MECHANO-GATED CHANNELS
- whose conformational state depends on mechanical forces that are applied to the
membrane
FOR NEXT DISCUSSION, we will focus more on the structure and function of voltage‐gated
potassium ion channels
Back in 1998, Roderick MacKinnon and his colleagues at Rockefeller University provided the
first atomic‐resolution image of an ion channel protein. But here the bacterial K + ion channel
called KcsA. The formulation of this structure led directly to an understanding of the mechanism
by which these remarkable molecular machines are able to select overwhelmingly for K + ions
over Na + ions, yet at the same time allow an incredibly rapid conductance of K + ions through
the membrane.
The KcsA potassium channel is a well-studied ion channel protein found in the membranes of
certain bacteria. It plays a crucial role in regulating the flow of potassium ions (K+) across the
bacterial cell membrane. The KcsA channel consists of four identical subunits arranged in a
symmetric fashion around a central pore. Each subunit is comprised of M1 and M2 helices
joined by a P (pore) segment consisting of a short helix and a nonhelical portion that lines the
channel through which the ions pass.
A portion of each P segment contains a conserved pentapeptide (GYGVT) whose residues line
the selectivity filter that screens for K + ions. The oxygen atoms of the carbonyl groups of these
residues project into the channel where they can interact selectively with K + ions within the
filter. As indicated in the top inset, the selectivity filter contains four rings of carbonyl O atoms
and one ring of threonyl O atoms; each of these five rings contains four O atoms, one donated
by each subunit. The diameter of the rings is just large enough so that eight O atoms can
coordinate a single K + ion, replacing its normal water of hydration. Although four K + binding
sites are shown, only two are occupied at one time.
Although there are four potential K + ion binding sites, only two are occupied at any given time.
Potassium ions are thought to move, two at a time, from sites 1 and 3 to sites 2 and 4. The entry
of a third K + ion into the selectivity filter creates an electrostatic repulsion that ejects the ion
bound at the opposite end of the line. Studies indicate that there is virtually no energy barrier
for an ion to move from one binding site to the next, which accounts for the extremely rapid flow
of ions across the membrane.
The hinge-bending model is a theoretical framework used to explain the opening and closing
mechanism of ion channels, such as the KcsA potassium channel. In this model, the channel's
structure is thought to undergo a specific type of conformational change, resembling the
movement of a hinge, to regulate the flow of ions. We have six helices that can be grouped into
two functionally distinct domains:
1. PORE DOMAIN- contains the selectivity filter that permits the selective passage of K +
ions.
2. VOLTAGE-SENSING DOMAIN- senses the voltage across the plasma membrane.
[DIANA]
FACILITATED DIFFUSION
A passive movement of molecules across a plasma membrane from a region of higher
concentration to a region of lower concentration without integrating energy.
To facilitate the diffusion process, a membrane-spanning protein called a facilitative
transporter lets the diffusing substance selectively bind in it. Then this transporter triggers a
conformational change to move the substance on the other side of the membrane.
These transporters have specific molecules that they transport, unlike ion channels
which conduct millions of ions per second, facilitative transporters move only about hundreds to
thousands of solute molecules per second across the membrane. When the concentration of
ions increases, the transport rate levels off to this maximum value, and the transporters are
saturated. The activities of these transporters can be regulated. Facilitated diffusion is
particularly important in mediating the entry and exit of polar solutes, such as sugars and amino
acids, that do not penetrate the lipid bilayer
An example of facilitated diffusion is the glucose transporters. The body’s primary source
of direct energy is glucose and most mammalian cells contain a membrane protein that
facilitates the diffusion of glucose from the bloodstream into the cell.
The solute concentration is directly proportional to the rate of solute movement during
simple diffusion and facilitated diffusion. However, the rate of solute movement is greater on the
facilitated diffusion than that of simple diffusion.
ACTIVE TRANSPORT
Unlike facilitated diffusion, however, the movement of a solute against a gradient
requires the coupled input of energy. Proteins that carry out active transport are often referred to
as “pumps.”
PRIMARY ACTIVE TRANSPORT: COUPLING TRANSPORT TO ATP HYDROLYSIS
Primary Active Transport - direct use of chemical energy (e.g. ATP) to transport molecules
across a membrane against their concentration gradient.
Jens Skou - discovered an ATP hydrolyzing enzyme in the nerve cells of a crab that was only
active in the presence of both Na+ and K+. This same enzyme was active in transporting two
ions and is called Na+/K+-ATPase or the sodium-potassium pump.
Sodium-potassium pumps result in an excess sodium ions outside the cell and excess
potassium ions inside the cell. The ratio of Na+ to K+ pumped by this Na+/K+-ATPase is 3:2
instead of 1:1. Thus, for every three sodium ions that are pumped out of the cell, two potassium
ions enter the cell. This is an example of a P-type ion pump wherein P stands for
phosphorylation which indicates that during the pumping cycle, ATP hydrolysis results in the
transfer of a released phosphate group to an aspartic acid residue of a transport protein. Note
that this Na+/K+-ATPase moves the molecules against its concentration gradient and it picks the
sodium and potassium ions from a region with low concentration to release it in a region with a
higher concentration.
Sodium-potassium pump can only be found in animal cells. The same ionic gradients are
used in non-excitable cells to power the movement of other solutes.
OTHER PRIMARY ION TRANSPORT SYSTEMS
The best-studied P-type pump is the Ca2+-ATPase where its three-dimensional structure
has been determined at several stages of the pumping cycle. It is present in the endoplasmic
reticulum membrane where it actively transports calcium ions out of the cytosol and releases it
into the lumen of this organelle.
Meanwhile, plants have H+-transporting, P-type, plasma membrane pump. This proton
pump is important in the secondary transport of solutes, in cytosolic pH control, and possibly in
cell growth through acidification of the plant cell wall.
On the other hand, sodium-potassium ATPase can also be seen in the epithelial lining of
the stomach which secretes a solution of concentrated acid into the stomach chamber.
Moreover, there is also another P-type pump, the H+/K+-ATPase in the epithelial lining of
the stomach to secret a solution of concentrated acid into the stomach chamber.
Unlike P-type pumps, V-type pumps utilize the energy of ATP without forming a
phosphorylated protein intermediate. It actively transports hydrogen ions across the walls of
cytoplasmic organelles and vacuoles. They also occur in membranes of other organelles where
they maintain the low pH of the contents, including the plasma membranes of a variety of cells.
In addition, V-type pumps that are found in the plasma membrane of the kidneys help to
maintain the body’s acid-base balance by secreting protons into the forming urine.
Another diverse group of proteins is ATP-binding cassette (ABC) transporters which
actively transport ions. All of the members of this superfamily share a homologous ATP-binding,
hence the name.
USING LIGHT ENERGY TO ACTIVELY TRANSPORT IONS
Bacteriorhodopsin - the first discovered and most studied light-driven proton pump. It
functions as a single molecule and is found in Halobacterium salinarium (or H. halobium). H.
halobium lives in extremely salty environments like the Great Salt Lake. The plasma membrane
of these prokaryotes turns into a purple color under anaerobic conditions because of the
presence of the protein bacteriorhodopsin. It contains a retina which absorbs light energy that
induces a series of conformational changes in the protein which cause a proton to move from
the retinal group to the exterior of the cell through a channel. Thus, it results in the translocation
of protons from the cytoplasm to the external environment, generating a steep H+ gradient
across the plasma membrane.
SECONDARY ACTIVE TRANSPORT (OR COTRANSPORT): COUPLING TRANSPORT TO
EXISTING ION GRADIENTS
The establishment of the concentration gradients like sodium, potassium, and hydrogen
provides a means to store free potential energy in a cell. Then, this energy is used by cells in
various ways to perform work which includes transporting solutes.
Cotransport = coupled movement of one molecule down its concentration gradient together
with a second molecule going against its concentration gradient.
TWO TYPES OF COTRANSPORT
Symport - two molecules are moving through the membrane protein in the same
direction (e.g. sodium-glucose transporter)
Na+ + glucose & H+ + sucrose
Antiport - two molecules are moving through the membrane protein in opposite
direction (e.g. sodium-calcium exchanger)
Exchangers - cotransporters that mediate antiport
[IVY]
● MEMBRANE POTENTIALS
● PROPAGRAN OF ACTION POTENTIALS AS AN IMPULSE
4.16 Membrane Potential
I.Parts of a Neuron
Nerve cells (or neurons )
- specialized for the collection, conduction, and
transmission of information, which is coded in the
form of fast‐moving electrical impulses.
- The nucleus of the neuron is located within an
expanded region called the cell body ,
which is the metabolic center of the cell and the site
where most of its material contents are manufactured.
Dendrites
- Extending from the cell bodies of most neurons
are a number of fine extensions
- receive incoming information from external
sources, typically other neurons.
Axon
single, more prominent extension
- Conducts outgoing impulses away from the cell body and toward the target cell(s).
- Most axons split near their ends into smaller processes, each ending in a terminal knob
—a specialized site where impulses are transmitted from neuron to target cell.
Terminal Knob
- allowing these brain cells to communicate with thousands of potential targets.
II.Membrane potential
-
-
-
-
-
-
refers to the difference in electrical charge between the inside and outside of a neuron,
which is created due to the unequal distribution of ions on both sides of the cell
membrane.
It is maintained through mechanisms like the sodium-potassium pump
The difference in electrical charge develops due to the grouping of ions on the inside and
outside of the membrane. (Ions are atoms that have either lost or gained electrons and
thus have a positive or negative charge)
There are positively charged sodium ions and negatively charged chloride ions. When a
neuron is at rest, the sodium ions and chloride ions are more prevalent outside of the
cell.
There are also positively charged potassium ions and various negatively charged ions,
often referred to as organic anions ( negatively charged ions). When a neuron is at rest,
the potassium ions and organic anions are more prevalent inside the cell.
At rest, the inside of the neuron is more negatively charged than the outside, causing the
resting membrane potential of an average neuron to be around -70 mV.
This is a transport protein that uses energy to constantly pump three sodium ions out of
the cell while at the same time pumping two potassium ions into the cell. Because there
are more positive ions being pumped out than negative, it helps to keep the membrane
potential negative.
Potassium will pass out of the neuron until it reaches the point where it is at an
equilibrium---when forces like diffusion aren’t pushing it in one direction or the other.
At this point, the membrane potential of the neuron is around -65 to -70 mV, which is
known as the resting membrane potential.
III.Resting potential
Voltage (or electric potential difference)
- A neuron at rest is negatively charged: the inside of a cell is
approximately 70 millivolts more negative than the outside (−70 mV,
note that this number varies by neuron type and by species). This
voltage is called the resting membrane potential; it is caused by
differences in the concentrations of ions inside and outside the cell.
- can be measured by inserting one fine glass electrode (or
microelectrode ) into the cytoplasm of a cell, placing another electrode
in the extracellular fluid outside the cell, and connecting the electrodes
to a voltmeter,
- Voltmeter- an instrument that measures a difference in charge between two points
- The difference in the number of positively charged potassium ions (K+) inside and
outside the cell dominates the resting membrane potential.
The presence of a membrane potential is not unique to nerve cells
-
such potentials are present in all types of cells, the magnitude varying between about
−15 and −100 mV.
Resting potential - a nerve or muscle cell is in an unexcited state, because it is subject
to dramatic change
IV.The Action Potential
Action potential
- The
understanding
of
membrane
potentials and nerve impulses rests on a
body of research carried out on the giant
axons of the squid in the late 1940s and
early 1950s by a group of British
physiologists, most notably Alan Hodgkin,
Andrew Huxley, and Bernard Katz.
- is a momentary reversal of membrane
potential that is the basis for signaling
within neurons.
- The energy required to create an action potential is stored ahead of time by the Na + /K
+ ‐ATPase, which generates steep ionic gradients across the plasma membrane.
- Once that is accomplished, the various ions are poised to flow through the membrane
down their respective electrochemical gradients as soon as their ion channels are
opened, just like water flowing from a dam once the flood‐gates are released.
The movements of ions across the plasma membrane of nerve cells form the basis for
neural communication.
A.Resting Potential
- The membrane in this region of the nerve cell exhibits the resting potential, in which only the
K+ leak channels are open and the membrane voltage is approximately −70 mV.
B.Depolarization Phase
- This opportunity for positively charged ions to move into the cell reduces the membrane
potential, making it less negative. Because the positive change in membrane voltage
causes a decrease in the polarity between the two sides of the membrane
- When neurotransmitters bind to receptors on the dendrites of a neuron, they can have
an effect on the neuron .This means that they make the membrane potential less
polarized, or cause it to move closer to 0.
- When neurotransmitters interacting with receptors cause repeated depolarization of the
neuron, eventually the neuron reaches what is known as its threshold membrane
potential. In a neuron with a membrane potential of -70 mV, this is generally around -55
mV.
-
-
When threshold is reached, a large number of sodium channels open, allowing
positively charged sodium ions into the cell. This causes massive depolarization of the
neuron as the membrane potential reaches 0 and then becomes positive.
The membrane has depolarized beyond the threshold value, opening the
voltage‐regulated sodium gates, leading to an influx of Na + ions .
The increased Na + permeability causes the membrane voltage to temporarily reverse
itself
Rising phase of the action potential
- influx of positive ions initiates the action potential, which then travels down the neuron.
- It is this reversal of membrane potential that constitutes the action potential.
Action potential reaches its peak
- sodium channels close and potassium channels open, which allow potassium to flow out
of the cell.
C.Repolarization (falling phase of the action potential)
- Within a tiny fraction of a second, the sodium gates are inactivated and the potassium
gates open, allowing potassium ions to diffuse across the membrane and establish an
even more negative potential at that location (−80 mV) than that of the resting potential.
- The loss of positive potassium ions promotes repolarization.The neuron returns to
resting membrane potential.
D.Hyperpolarized. (refractory period)
- When the neuron overshoots it the cell becomes hyperpolarized. It is very difficult to
cause the neuron to fire again.
E. Resting membrane potential
- Eventually the potassium channels close and the membrane returns to resting
membrane potential, ready to be activated again. The signal generated by the action
potential travels down the neuron and can cause the release of neurotransmitters at the
axon terminals to pass the signal to the next neuron.
4.17 Propagation of Action Potentials as an Impulse
Once an action potential has been initiated, it does not remain localized at a particular site but is
propagated as a nerve impulse down the length of the cell to the nerve terminals.
An action potential at one site on the membrane
depolarizes an adjacent region of the membrane, triggering
an action potential at the second site. The action potential
can only flow in the forward direction because the portion of the membrane that has just
experienced an action
potential remains in a refractory period.
●
●
●
●
●
An action potential is propagated in one direction along the axon
During an action potential the inside of the cell membrane becomes positive with respect
to the outside
An action potential generates local currents that tend to depolarize the membrane
immediately adjacent to the action potential
When depolarization caused by the local currents reaches threshold a new action
potential is produced adjacent to the original one
Action potential propagation occurs in one direction because the recently depolarized
area of the membrane is in absolute refractory period and cannot generate an action
potential
During the evolution of vertebrates, an increase in conduction velocity was achieved when the
axon became wrapped in a myelin sheath
Myelin sheath
- it is composed of many layers of lipid‐containing membranes,
- ideally suited to prevent the passage of ions across the plasma membrane.
Nodes of Ranvier
- nearly all of the Na + ion channels of a myelinated neurons reside in this unwrapped
gaps, between adjacent Schwann cells or oligodendrocytes that make up the sheath
- the only sites where action potentials can be generated.
- Here ions can flow with ease, the density of voltage-gated Na channels is very high in
this area.
Saltatory conduction
- An action potential at one node triggers an action potential at the next node causing the
impulse to jump from node to node without having to activate the intervening membrane.
- Propagation of an impulse by this mechanism is called saltatory conduction.
- Impulses are conducted along a myelinated axon at speeds up to 120 meters per
second, which is more than 20 times faster than the speed that impulses travel in an
unmyelinated neuron of the same diameter.
REFERENCES:
● Karp, G., Iwasa, J., & Marshall, W. (2019). Karp’s cell and Molecular Biology: Concepts
and Experiments. Wiley.
● Lumen Learning. (n.d.). Resting Membrane Potential | Biology for Majors II. Retrieved
from
●
●
●
https://courses.lumenlearning.com/wm-biology2/chapter/resting-membrane-potential/?fb
clid=IwAR1CFx_z-Jx9AbzdpYmv3wJqqR8c28KORibrLEvHNVSuDsS2eFFLzL8Wn8E
Neuroscientifically Challenged (2014). 2-Minute Neuroscience: Membrane Potential.
Retrieved from
https://neuroscientificallychallenged.com/posts/2-minute-neuroscience-membrane-potent
ial
Neuroscientifically Challenged (2014). 2-Minute Neuroscience: Action Potential.
Retrieved from
https://neuroscientificallychallenged.com/posts/2-minute-neuroscience-membrane-potent
ial-action-potential
Nonstop Neuron (2021). Propagation of Action Potential. Retrieved from
https://www.nonstopneuron.com/post/propagation-of-action-potential
[STEVEN] NEUROTRANSMISSION: JUMPING THE SYNAPTIC CLEFT
Neurotransmission is the transfer of information between neurons. Neurons are linked with
their target cells at specialized junctions called synapses. Careful examination of a synapse
reveals that the two cells do not make direct contact but are separated from each other by a
narrow gap of about 20 to 50 nm. This gap is called the synaptic cleft. A presynaptic cell (a
receptor cell or a neuron) conducts impulses toward a synapse, and a postsynaptic cell (a
neuron, muscle, or gland cell) always lies on the receiving side of a synapse. A number of
synapses between the terminal branches of an axon and a skeletal muscle cell are called
neuromuscular junctions.
How does an impulse in a presynaptic neuron jump across the synaptic cleft and affect the
postsynaptic cell? Studies carried out decades ago indicated that a chemical substance is
involved in the transmission of an impulse from one cell to another. The very tips (terminal
knobs) of the branches of an axon appear in the electron microscope to contain large numbers
of synaptic vesicles that serve as storage sites for the chemical transmitters that act on
postsynaptic cells. Two of the best-studied neurotransmitters are acetylcholine and
norepinephrine, which transmit impulses to the body’s skeletal and cardiac muscles.
What initiates the process of neurotransmission? Action potentials are the rapid sequence
changes in the voltage across the membrane and these spike-like events or nerve impulses are
what initiates neurotransmission.
In response to the appropriate stimulus, the cell membrane of a nerve cell goes through a
sequence of depolarization from its rest state followed by repolarization to that rest state. In the
sequence, it actually reverses its normal polarity for a brief period before reestablishing the rest
potential. The action potential sequence is essential for neural communication. The simplest
action in response to thought requires many such action potentials for its communication and
performance. For modeling the action potential for a human nerve cell, a nominal rest potential
of -70 mV will be used. The process involves several steps:
Going back, what are neurotransmitters? Neurotransmitters are chemical messengers that
your body can’t function without. Their job is to carry chemical signals (“messages”) from one
neuron (nerve cell) to the next target cell. The next target cell can be another nerve cell, a
muscle cell or a gland. These messages help you move your limbs, feel sensations, keep your
heart beating, and take in and respond to all information your body receives from other internal
parts of your body and your environment.
Presented are some of the most well-known
neurotransmitters, however, there are in fact
over 100 known agents that can act as
neurotransmitters. In general, communication
between neurons in the brain is accomplished
by the movement of neurotransmission
chemicals across the gap (synapse) between
them. They are released from the ‘terminal’ of
one neuron, and accepted by the receptor on
the next neuron. The effect that this process
has
will
depend
on
the
class of
neurotransmitter.
Neurotransmitters transmit one of three possible actions in their messages, depending on the
specific neurotransmitter.
●
●
●
Excitatory: Excitatory neurotransmitters “excite” the neuron and cause it to “fire off the
message,” meaning, the message continues to be passed along to the next cell.
Examples of excitatory neurotransmitters include glutamate, epinephrine and
norepinephrine.
Inhibitory: Inhibitory neurotransmitters block or prevent the chemical message from
being passed along any further. Gamma-aminobutyric acid (GABA), glycine and
serotonin are examples of inhibitory neurotransmitters.
Modulatory: Modulatory neurotransmitters influence the effects of other chemical
messengers. They “tweak” or adjust how cells communicate at the synapse. They also
affect a larger number of neurons at the same time.
Sequence of Events During Synaptic Transmission
As shown in Figure 4.57, during steps 1–4, a nerve impulse reaches the terminal knob of the
axon, calcium gates open leading to an influx of Ca 2+, and acetylcholine is released from
synaptic vesicles and binds to receptors on the postsynaptic membrane. If the binding of the
neurotransmitter molecules causes a depolarization of the postsynaptic membrane (as in 5a), a
nerve impulse may be generated there (6). If, however, the binding of a neurotransmitter causes
a hyperpolarization of the postsynaptic membrane (5b), the target cell is inhibited, making it
more difficult for an impulse to be generated in the target cell by other excitatory stimulation.
The breakdown of the neurotransmitter by acetylcholinesterase is not shown. This could be
seen, however, in Figure 4.58. In steps 6 and 7, most of the neurotransmitters are reuptaken or
brought back into the presynaptic neuron while the remaining neurotransmitters are broken
down by enzymes in the postsynaptic neuron.
Here is a more detailed explanation of the procedures of synapsis transmissions with the
neurotransmitter acetylcholine. When an impulse reaches a terminal knob (step 1, Figure 4.57),
the accompanying depolarization induces the opening of a number of voltage‐gated Ca2+
channels in the plasma membrane of this part of the presynaptic nerve cell (step 2, Figure 4.57).
Calcium ions are normally present at very low concentrations within the neuron (about 100 nM),
as in all cells. When the gates open, calcium ions diffuse from the extracellular fluid into the
terminal knob of the neuron, causing the [Ca 2+] to rise more than a thousandfold within
localized microdomains near the channels. The elevated [Ca 2+] triggers the rapid fusion of one
or a few nearby synaptic vesicles with the plasma membrane, causing the release of
neurotransmitter molecules into the synaptic cleft (step 3, Figure 4.57).
Once released from the synaptic vesicles, the neurotransmitter molecules diffuse across the
narrow gap and bind selectively to receptor molecules that are concentrated directly across the
cleft in the postsynaptic plasma membrane (step 4, Figure 4.57). A neurotransmitter molecule
can have one of two opposite effects depending on the type of receptor on the target cell
membrane to which it binds:
● The bound transmitter can trigger the opening of cation‐selective channels in the
membrane, leading primarily to an influx of sodium ions and a less negative (more
positive) membrane potential. This depolarization of the postsynaptic membrane excites
the cell, making the cell more likely to respond to this or subsequent stimuli by
generating an action potential of its own (Figure 4.57, steps 5a and 6).
● The bound transmitter can trigger the opening of anion‐selective channels, leading
mainly to an influx of chloride ions, and a more negative (hyperpolarized) membrane
potential. Hyperpolarization of the postsynaptic membrane makes it less likely the cell
will generate an action potential because greater sodium influx is subsequently required
to reach the membrane’s threshold (Figure 4.57, step 5b).
Actions of Drugs on Synapses
Psychoactive drugs affect the brain and personality by either increasing or decreasing
postsynaptic transmissions
● Drugs that increase neurotransmission levels are called stimulants and increase
psychomotor arousal and alertness
● Drugs that decrease neurotransmission levels are called depressants and slow down
brain activities and relax muscles
Stimulant drugs mimic the stimulation provided by the sympathetic nervous system (i.e. 'fight
or flight’ responses) Examples of stimulants include caffeine, cocaine, amphetamines, ecstasy
(MDMA) and nicotine.
● Nicotine
○ Nicotine stimulates the cholinergic pathways by mimicking the action of
acetylcholine (binds Ach receptors)
○ Nicotine is not broken down by the enzyme acetylcholinesterase, resulting in
overstimulation of Ach receptors
○ Nicotine raises dopamine levels in the brain (leading to addiction) and activates
parasympathetic pathways (calming effect)
● MDMA (ecstasy)
○ MDMA binds to reuptake pumps on presynaptic neurons and blocks the recycling
of dopamine and serotonin (5-HT)
○ MDMA also enters the presynaptic neurons via the reuptake pumps and triggers
the secretion of neurotransmitter
○ This increases levels of neurotransmitter in the synaptic cleft, prompting feelings
of euphoria and heightened sensation
○ MDMA (ecstasy) is a recreational drug known to increase the activity of specific
neurotransmitters – serotonin and dopamine
■
■
○
Serotonin (5-HT) is found in regions of the brain associated with sleep
and emotion and is involved in regulating mood
Dopamine is involved in the brain’s reward pathway and plays an
important role in regulating motivation and pleasure
MDMA binds to reuptake pumps and increases the release of neurotransmitters
whilst slowing its rate of uptake
■ This causes overstimulation of post-synaptic receptors until
neurotransmitter reserves are depleted
■ Long-term usage of MDMA can cause adverse changes to brain
architecture and result in cognitive impairment
In contrast, depressants reduce stimulation of the central nervous system and may induce
sleep (sedatives). Examples of sedatives include benzodiazepines, barbiturates, alcohol and
tetrahydrocannabinol (THC = cannabis)
● Benzodiazepine
○ Benzodiazepines bind to GABA receptors on the post-synaptic neuron and
increase the efficiency of GABA action
○ GABA triggers the opening of chloride channels to cause hyperpolarisation –
benzodiazepines enhance this effect
○ Benzodiazepines promote sleep-inducing and muscle relaxing responses by the
body
○
● Tetrahydrocannabinol (THC)
○ THC mimics the neurotransmitter anandamide by binding to cannabinoid
receptors on presynaptic neurons
○ Anandamide (and THC) blocks the release of inhibitory neurotransmitters that
prevent dopamine secretion
○ By preventing the inhibition of dopamine secretion, THC causes a sense of
euphoria and emotional well-being.
Synaptic Plasticity
While synapses are often perceived as fixed, unchanging structures, they can display a
remarkable dynamic quality known as “synaptic plasticity.” Synaptic plasticity is particularly
important during infancy and childhood, when the neuronal circuitry of the brain achieves its
mature configuration. It is the ability of neurons to modify the strength of their connections and is
an important neurophysiological process involved in brain networks development and
reorganization after damage.
Long-term synaptic plasticity was first reported in 1973. Studying a pathway in the rabbit
hippocampus, researchers discovered that rapidly and repeatedly activating the synapses made
them stronger; the volume control was turned up and stayed that way. They called this
long-lasting increase in synaptic strength long-term potentiation, or LTP. The reverse
phenomenon, in which synapses become weaker for extended periods, also exists, and is
called long-term depression, or LTD.
The strength of synapses can be increased or decreased, and whether or not and in which
direction they change depends on their activity patterns. Very active synapses are likely to
become stronger (LTP), and those that are less active, or less effective at causing an action
potential, tend to become weaker (LTD). Long-term synaptic plasticity forms the model for
memory storage.
After a neuron fires an action potential, there are three main steps to synaptic transmission:
● Neurotransmitter release
● Binding of neurotransmitter to postsynaptic receptors, and
● Opening of ion channels in the postsynaptic neuron, which allows electrical currents to
flow in or out of the cell.
As seen in the diagram above, synaptic plasticity can change either the amount of
neurotransmitter released (1) or the number of postsynaptic receptors available (2). Both have
the effect of altering how much electrical current flows through the ion channels (3); in other
words, these processes change synaptic strength.
[MEL] EXTRACELLULAR MATRIX
Most cells, whether eukaryotic or prokaryotic, have extracellular structures formed from
materials transported across the plasma membrane. These structures provide physical support.
In animals, it's the extracellular matrix (ECM) made of collagen and proteoglycans. In
plants and fungi, it's the rigid cell wall consisting of cellulose microfibrils and other
polysaccharides with some protein. The majority of bacteria and archaea are enveloped
by an external formation referred to as a cell wall. Nevertheless, bacterial cell walls are
primarily composed of peptidoglycans rather than cellulose.
Cellular variations correspond to organisms' lifestyles. Plants, which are immobile, utilize
rigid cell walls. Animals, needing mobility for survival, lack rigid walls but have an elastic
collagen network. Bacteria and archaea, regardless of motility, reside in hypotonic
environments, using cell walls for rigid support and protection from osmotic pressure.
The animal cell's extracellular matrix (ECM) composition varies with cell type. Collagen is highly
abundant in vertebrate tissues like tendons and bones. The ECM primarily offers support but
also regulates cell functions such as motility, division, recognition, adhesion, and
embryonic development through its component types and arrangements.