Topics Covered
Electrophysiology:
• Concepts of cell
• Cell membrane
• Ion channel
• Resting and action potentials.
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Structure level of human body
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The components of cell
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The components of cell
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The components of cell
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CELL MEMB.
How does the Cell Membrane Look Like?
They cannot see it….But they could make observations and
deductions:
1-Observation:
Lipid and lipid soluble materials enter cells more rapidly than
substances that are insoluble in lipids.
Deductions
Membranes are made of lipids.
Fat-soluble substance move through the membrane by dissolving in it
("like dissolves like").
2-Observation:
Phospholipids are Amphipathic: molecule has both a hydrophilic
region and a hydrophobic region.
Phospholipids
will form an artificial membrane on the surface of water
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with only the hydrophilic heads immersed in water.
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CELL MEMB.
How does the Cell Membrane Look Like?
Deductions:
Because of their molecular structure,
phospholipids can form membranes.
3-Observation:
Phospholipid content of membranes
isolated from red blood cells is just
enough to cover the cells with two layers.
Membranes isolated from red blood cells
contain proteins aswell as lipids
Deductions:
Cell membranes are phospholipid
bilayer, two molecules thick.
There is protein in biological
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membranes.
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CELL MEMB.
Components of Cell Membrane
The major components of all cellular membranes are lipids and proteins.
Lower concentration of carbohydrates are present.
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Membranes contain a mix of phospholipids and each leaflet has a different
phospholipid composition.
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CELL MEMB.
The Fluid Mosaic Model
It was proposed bySinger &Nicolson (1972).
It is the model that is currently accepted.
“Thebiological membranescan beconsidered asa two-dimensional liquid where all
lipid and protein moleculesdiffuse moreorless freely”.
The membrane has 2 major molecular components:
Lipids = mostly phospholipids &cholesterol.
Proteins =
A. Integral (intrinsic).
B. Peripheral (extrinsic).
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CELL MEMB.
The Fluid Mosaic Model
The membrane is described as a fluid, owing to the ability of lipids to diffuse
laterally within the plane of the membrane.
The overall structure is likened to a flowing sea. And, like a mosaic,
membrane proteins are dispersed throughout the membrane.
Many of the membrane proteins retain the ability to undergo lateral motion
and are likened to icebergs floating within the sea of lipids.
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CELL MEMB.
Membrane Lipids
They are the most abundant type of macromolecule present (40% and
80%).
Provide both the basic structure and the framework of the membrane and
regulate its function.
Three types of lipids are found in cell membranes: phospholipids,
cholesterol, and glycolipids.
1. Phospholipids:
The most abundant of the membrane lipids.
They are polar, ionic compounds that are amphipathic in nature. That is,
each has a hydrophilic head, which is the phosphate group plus whatever
alcohol is attached to it (for example, serine, ethanolamine, and choline)
and along, hydrophobic tail containing fatty acids.
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CELL MEMB.
Membrane Lipids
While the polar head groups of the outer leaflet
extend outward toward the environment, the fatty
acid tails extend inward.
The basic structure of cell membranes is a phospholipid
bilayer. Two antiparallel sheets of phospholipids form
the membrane that surrounds the contents of the cell.
The layer closest to the cytosol is the inner leaflet
while the layer closest to the exterior environment is
the outer leaflet.
Phospholipids that present in the plasma membrane:
A. Glycerol PL  Phospholipids contain glycerol. E.g.:
phosphatidylserine,
phosphatidylethanolamine,
phosphatidylinositol, and phosphatidylcholine.
B. Sphingo PL Phospholipids contain sphingosine.
E.g.: sphingomyelin.
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CELL MEMB.
Membrane Lipids
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CELL MEMB.
Membrane Lipids
2. Cholesterol
An amphipathic molecule, cholesterol contains a polar
hydroxyl group as well as a hydrophobic steroid ring
and attached hydrocarbon.
It is dispersed throughout cell membranes,
intercalating between phospholipids. Its polar
hydroxyl group is near the polar head groups of the
phospholipids while the steroid ring and hydrocarbon
tails of cholesterol are oriented parallel to those of
the phospholipids.
It fits into the spaces created by the kinks of the
unsaturated fatty acid tails, decreasing the ability of
the fatty acids to undergo motion and therefore
causing stiffening and strengthening of the membrane.
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CELL MEMB.
Membrane Lipids
3. Glycolipids:
Lipids with attached carbohydrate (sugars), glycolipids are found in
cell membranes in lower concentration than phospholipids and
cholesterol.
The carbohydrate portion is always oriented toward the outside of the
cell, projecting into the environment.
Glycolipids help to form the carbohydrate coat observed on cells and
are involved in cell-to-cell interactions.
They are a source of blood group antigens and can act as receptors for
toxins including those from cholera and tetanus.
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CELL MEMB.
Membrane Proteins
Proteins are largely responsible for many biological functions of the
membrane. For example, some membrane proteins function in transport of
materials into and out of cells. Others serve asreceptors for hormones.
The types of proteins within a plasma membrane vary depending on the cell
type. However, all membrane proteins are associated with membrane in one
of three main ways.
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CELL MEMB.
Membrane Association Proteins
1- Integral proteins:
They are inserted into membrane, so their hydrophobic regions are
surrounded byhydrocarbon portions of phospholipids.They maybe:
Unilateral, reaching only part wayacross themembrane.
Transmembrane, with hydrophobic midsections between hydrophilic
ends exposed on both sides.
These proteins are oriented with their hydrophilic portions in contact
with the aqueous exterior environment and with the cytosol and their
hydrophobic portions in contact with the fatty acid tails of the
phospholipids.
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CELL MEMB.
Membrane Proteins
1- Integral proteins:
Integral proteins are difficult to remove from membrane.
Youmust use detergents to dissolve integral membrane away.
The membrane is destroyed while extracting integral proteins.
2- Peripheral proteins:
They are not embedded but attached to the membrane's surface.
May be attached to integral proteins.
On cytoplasmic side, may be held by filaments of cytoskeleton.
They are easy to remove from membrane when treated with high salt and the
membrane is not destroyed.
Such as those involved in the spectrin membrane skeleton of erythrocytes.
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CELL MEMB.
Membrane Proteins
3. Lipid-anchored proteins:
They are attached covalently to a portion of a lipid without entering the core
portion of the bilayer of the membrane.
Both transmembrane and lipid-anchored proteins are integral membrane
proteins since they can only be removed from a membrane by disrupting the
entire membrane structure.
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CELL MEMB.
Membrane Proteins Functions
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CELL MEMB.
Functions of Membrane Proteins
1-Transport:
(a) A protein that spans the membrane may provide a
hydrophilic channel across the membrane that is selective for
a solute.
(b) Other transport proteins shuttle a substance from one
side to the other by changing shape. Some of these proteins
hydrolyze ATP as an energy source to actively pump
substances across the membrane.
2-Enzymatic activity:
A peripheral protein built into the membrane may be an
enzyme with its active site exposed to substances in the
adjacent solution. In some cases, several enzymes in a
membrane are organized as a team that carries out sequential
steps of ametabolic pathway.
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CELL MEMB.
Functions of Membrane Proteins
3-Signal transduction:
A membrane Lipid-anchored protein may have a binding
site with a specific shape that fits the shape of a chemical
messenger, such as a hormone. The external messenger
(signal) may cause a conformational change in the protein
(receptor) that relays the message to the inside of the
cell.
They include the G proteins, which are named for their
ability to bind to guanosine triphosphate (GTP) and
participate in cell signaling in response to certain
hormones.
4- Cell-cell recognition:
Some glycoproteins serve as identification tags that are
specifically recognized byother cells.
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CELL MEMB.
Functions of Membrane Proteins
5- Intercellular joining:
Membrane proteins of adjacent cells mayhook together
in various kinds of junctions, such as gap junctions or
tight junctions.
6-
Attachment to
the
cytoskeleton
and
extracellular Matrix (ECM):
Microfilaments or other elements of the cytoskeleton
may be bonded to peripheral membrane proteins, a
function that helps maintain cell shape and stabilizes
the location of certain membrane proteins.
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Proteins that adhere to the ECM can coordinate
extracellular and intracellular changes.
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Membrane Carbohydrates & Cell-Cell Recognition
CELL MEMB.
They are usually branched oligosaccharides.
Some are covalently bonded to lipids (glycolipids), most are covalently
bonded to proteins (glycoproteins).
Vary from species to species, between individuals of the same species and
among cells in the same individual.
Cell-Cell Recognition:
Cell-cell recognition is the ability of a cell to determine if other cells it
encounters are alike or different from itself.
Cell-cell recognition is crucial in the functioning of an organism as it is the
basis for sorting of an animal embryo's cells into tissues and organs and the
rejection of foreign cells bythe immune system.
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CELL MEMB.
Membrane Carbohydrates & Cell-Cell Recognition
Recognition:
The way cells recognize other cells is probably by keying on cell markers
found on the external surface of the cell membrane. Because of their
diversity and location, membrane carbohydrates are good candidates.
The blood grouping A, B, AB and O are based on oligosaccharides found
on the RBC’s membrane.
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CELL MEMB.
The
Membrane
Fluidity
Membranes are held together byhydrophobic interactions.
Most membrane lipids and some proteins can drift laterally within the
membrane.
Molecules rarely flip transversely across the membrane, because
hydrophilic parts would haveto cross the membrane's hydrophobic core.
Lipid Movements:
• Phospholipids can drift laterally in the plane of
the membrane (an average lipid molecule can
diffuse the length of a large bacterial cells (~ 2 μm)
in about 1 second) = lateral movement (frequently)
• Also, phospholipids can migrate from the
monolayer on one side to that on the other = flipflop (rarely).
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CELL MEMB.
Lipid Movements:
The Membrane Fluidity
Temperatureand lipid compositiondetermine fluidity of the membrane.
-At low temperature, membrane is less fluid and because the phospholipids
are more closely packed.
• Membranes rich in unsaturatedfatty
acids are;
more fluid that those dominated by
saturated.
fatty acids because the kinks in the
unsaturated.
fatty acid tails prevent
packing.
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The
Membrane
Fluidity
Lipid Movements:
Steroid cholesterol which is wedged
between
phospholipids
also
effects
• membrane fluidity.
At warm temperature, it makes membrane less fluid by
restraining the movement of phospholipid.
At low temperature, the membrane
remains fluid
because cholesterol hinders the close packing of the
phospholipids.
Membrane proteins drift more slowly than lipids
•
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Ion Channels
Proteins are the constituents of pumps and channels that exchange
ions between intracellular and extracellular space. The ions themselves
have radii on the order of 1 𝐴° where the channel structure is on the
order of 100 𝐴° and thickness 75 𝐴° .
• The passage of ions through the membrane is regulated by:
• Pumps and exchangers
• Channels
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Ion Channels
• Pumps and exchangers:
The purpose of pumps and exchangers is to maintain the difference intra-and extracellular ionic concentrations.
Pumps are active processes (i.e., they consume energy) that move against the
concentration gradients of ions. Exchangers use the concentration gradient of one
ion to move another ion against its concentration gradient. The major ion
transporters are: Na+-K+ pump, Na+-Ca2+exchanger, Ca2+ pump, BicarbonateCl−exchanger, Cl−-Na+-K+ co-transporter.
• Channels:
Channels are passive processes that allow ions to pass through the membrane under
the influence of concentration and electric potential gradients. Channels exhibit
selective permeability, i.e., they only allow certain ions to pass through them. Ion
channel gates regulate the permeability of channels, allowing control over the flow
of particular ion.
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Voltage gated ion channel structure
Voltage gated ion channels are made of there basic
parts:
i. Trans membrane pore
ii. Voltage sensor
iii. Selectivity filter
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Resting potential
• http://faculty.washington.edu/chudler/ap.html
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Resting potential
• The Resting Potential in cells are normally more negative
inside than outside. This varies from -9mV to -100mV. This is
just the opposite of osmolarity
• Excitable tissues of nerves and muscles cells have higher
potentials than other cells (epithelial cells and connective
tissue cells).
• Dead cells do not have membrane potentials.
• The membrane potential is due to the sodium ions found
in the extracellular matrix and the potassium ions found
in the intracellular matrix
• A cell is “polarized” because the interior (ICF) side of the
membrane is relatively more negative than the exterior
(ECF).
Where does the resting membrane potential come from?
The resting membrane potential is determined by the uneven
distribution of ions (charged particles) between the inside and
the outside of the cell, and by the different permeability of the
membrane to different types of ions.
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Resting Potential
The properties of semipermeable cell
membrane give raise to a high potassium and
low sodium ion concentration in the
intracellular region. It results a potential
difference of about - 0.1 V between the inside
and outside of the membrane. It is said to be
polarized. The membrane potential at the
polarized state is called resting potential. The
potential is maintained until some kind of
disturbance upsets the equilibrium.
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Resting potential
• Membrane potentials are due to
the diffusion of ions down their
concentration gradients, the
electric charge of the ion, and any
membrane pumps for that ion.
• Influx is the net movement of ions into
the cell from the ECF.
• Efflux is the net movement of ions out
of the cell to the ECF.
• Flux (the movement of charges) is
always measured in millivolts (mV).
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Action Potentials (APs)
• A brief change in membrane potential from -70mV(resting) to +30mV
(hyperpolarization)
• Action potentials are only generated by muscle cells and neurons
• They do not decrease in strength over distance
• An action potential in the axon of a neuron is a nerve impulse
• An action potential is a rapid rise and subsequent fall in voltage or
membrane potential across a cellular membrane with a characteristic
pattern. Sufficient current is required to initiate a voltage response in
a cell membrane; if the current is insufficient to depolarize the
membrane to the threshold level, an action potential will not fire.
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Phases of the Action Potential
• 1 – resting state
• 2 – depolarization
phase
• 3 – repolarization
phase
• 4 – hyperpolarization
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Action Potential: Step 1 Resting State
• Na+ and K+ channels are
closed
• Leakage accounts for small
movements of Na+ and K+
• Each Na+ channel has two
voltage-regulated gates
• Activation gates –
closed in the resting
state
• Inactivation gates –
open in the resting
state
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Figure 11.12.1
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Action Potential: Step 2 Depolarization Phase
• The local depolarization current
flips open the sodium gate and
Na+ rushes in.
• Threshold: when enough Na+ is
inside to reach a critical level of
depolarization (-55 to -50 mV)
threshold, depolarization
becomes self-generating.
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Figure 11.12.2
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Action Potential: Step 2 Cont.
• Na + will continue to rush in making
the inside less and less negative and
actually overshoots the 0mV
(balanced) mark to about +30mV.
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Action Potential: Step 3 Repolarization Phase
• After 1 ms enough Na+ has entered that positive charges resist
entering the cell.
• Sodium inactivation gates close and membrane permeability to Na+
declines to resting levels
• As sodium gates close, voltage-sensitive K+ gates open
• K+ exits the cell and
internal negativity
of the resting neuron
is restored
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Figure 11.12.3
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Action Potential: Step 4 Hyperpolarization
• Potassium gates are slow and remain open, causing an excessive
efflux of K+
• This efflux causes hyperpolarization of the membrane (undershoot).
• The neuron is
insensitive to
stimulus and
depolarization
during this time
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Figure 11.12.4
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Action Potential:
Role of the Sodium-Potassium Pump
• Repolarization
• Restores the resting electrical conditions of the neuron
• Does not restore the resting ionic conditions
• Ionic redistribution back to resting conditions is restored by the
sodium-potassium pump
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Propagation of an Action Potential
• When one area of the cell membrane has begun to return to resting
the positivity has opened the Na+ gates of the next area of the
neuron and the whole process starts over.
• A current is created that depolarizes the adjacent membrane in a
forward direction
• The impulse propagates away from its point of origin
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Propagation of an Action Potential (Time = 0ms)
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Figure 11.13a
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Propagation of an Action Potential (Time = 1ms)
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Propagation of an Action Potential (Time = 2ms)
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