Plasma Membrane Dynamics and Cell Transport Mechanisms
Plasma Membranes are mostly Lipids and Proteins arranged in a Fluid Mosaic Model
A typical cell membrane has a composition of:
Lipids: 40-60% - arranged in a double lipid bilayer.
Protein: 30-50% - proteins which are inserted either partly or completely through bilayer.
Carbohydrate: 5-10% - carbohydrates which attach to extracellular fluid (ECF) side.
These percentages can vary significantly depending on the specific type of cell in the body.
Plasma membrane
ECF
ICF
Nucleus
Cytoplasm with organelles
Figure 1. This is the typical diagrammatic representation of a eukaryotic cell. The extracellular fluid
(ECF) is kept separate from the intracellular fluid (ICF) by the plasma membrane.
General Function of Plasma Membranes
1. Physical Barrier: The plasma membrane (PM) acts as a barrier; it separates the inside of the cell,
containing ICF, from the outside of the cell, containing ECF. It creates the boundary of the cell and
isolates it from other cells and structures.
2. Regulation of Exchange: Anything that goes into or out of a cell must do so by crossing the plasma
membrane. Exchange with the environment occurs across this membrane, either by slipping through
the membrane or by being transported across by protein channels or protein carriers.
3. Structural Support: Structural proteins are tethered to the internal or intracellular aspect of the plasma
membrane in order to create the internal structural support for the cell. This internal framework is
referred to as the cytoskeleton of the cell. For example, this helps create the shape of cells, like the
distinctive biconcave disc shape of the red blood cell.
4. Communication and Cell ID: Signals from the external environment of the cell are transferred into
the internal compartment across the plasma membrane. This often involves receptors that sit on the
external aspect of the plasma membrane to receive the signal. Signal molecules are called ‘ligands’
and they bind to receptors, much like substrates bind to enzymes. There are also molecules
(glycoproteins and glycolipids) which attach to the external surface of the plasma membrane to help
identify the cell as self. For example, these flags or markers are what make up the blood typing of a
red blood cell (A, B, AB or O).
Membrane Lipids
1. Phospholipids - usually about 75% of lipid content.
The polar glycerol-phosphate head of a phospholipid is the hydrophilic end and a nonpolar fatty acid tail
is the hydrophobic end. The entire molecule is amphiphilic, meaning it can mix with both water and lipid
environments. The phospholipids are arranged in two rows, called the lipid bilayer and this functions as a
barrier that only lipid-soluble molecules can penetrate. They also provide a framework for membrane
2
proteins. Some lipids are involved in cellular communication. Some common phospholipids found in
plasma membranes include phosphatidyl choline and sphingomyelin.
2. Cholesterol - usually about 20 - 30% of lipid content.
This 4 ringed lipid structure inserts into the hydrophobic center with the nonpolar fatty acid tails. The
more cholesterol in the plasma membrane the more insulative the membrane will be. For example, the
myelin sheath membrane (which insulates axons of nerve cells) is about 30% cholesterol, while other
mammalian cell membranes may be about 20% cholesterol.
Cholesterol helps to stabilize the plasma membrane. It functions to keep membranes impermeable and yet
flexible. Membranes with higher cholesterol concentrations are less permeable to ions, water, and other
small molecules. Presumably cholesterol blocks the openings between phospholipid tails through which
these small molecules could otherwise pass. Mammals maintain a relatively constant Tb, so the
"plasticizing" effect of cholesterol is not as important as it is in poikilothermic animals and plants that
cannot maintain a constant body temperature.
3. Glycolipids – usually about 5% of the lipid content.
The prefix glyco means ‘glucose’ or ‘sugar’, so a glycolipid is a small amount of a sugar attached to a
large amount of lipid. Glycolipids are found on the external surface of the plasma membrane and act as a
cell markers. This helps identify the cell as self to defense cells of the body.
Other Phospholipid Arrangements
1. Micelles are small droplets with hydrophobic tails forming the interior; the hydrophilic heads form the
exposed boundary. Important in digestion and absorption of fats in digestive tract.
2. Liposomes are larger hollow spheres with phospholipid bilayer walls. Their hollow core can be loaded
with water-soluble molecules. Can be used as a drug delivery system.
Membrane Carbohydrates
Plasma membrane carbohydrates attach to both lipids and proteins. The Glycocalyx is a protective layer
on cell surface formed by Glycoproteins - when glucose attached to membrane proteins and Glycolipids
- when glucose attached to membrane lipids. The carbohydrates of the glycocalyx play a critical role in
identifying cells; for example, the carbohydrates of the glycocalyx in human blood cells differentiate the
main ABO blood groups from one another.
Membrane Proteins
1. Associated Proteins
Also termed peripheral or extrinsic proteins. They are attached loosely to membrane-spanning proteins or
to polar regions of phospholipids. They do not span the plasma membrane!
2. Integral Proteins and Membrane-Spanning Proteins
Also termed intrinsic proteins. These are tightly bound into the phospholipid bilayer. Some integral
proteins only extend partway into the membrane, others are membrane-spanning. Membrane-spanning
proteins have segments that cross the membrane multiple times. Loops extend into extracellular and
intracellular regions. Carbohydrates attach to extracellular loops and phosphates attach to intracellular
loops. When amino acids are linked to each other, they can form an -helix that has an exterior layer of
nonpolar side groups and a central core composed of the polar amino and carboxyl groups. This ties the
protein so firmly to the membrane that it can only be freed by disrupting the phospholipid bilayer with
detergents.
3
Membrane receptors, transporters, and enzymes are grouped into families according to how many
membrane-spanning regions they possess. Below are some examples:
1) The voltage-gated K+ channel has six transmembrane segments.
2) The voltage-gated Na+ and Ca2+ channels have four associated segments (domains), each with six
membrane-spanning regions.
3) The ATPase transporters of eukaryotic cells have 8-10 membrane-spanning regions.
4) The G-protein-linked membrane receptors all have seven transmembrane segments, as do the 2adrenergic and rhodopsin receptors.
Originally it was thought that membrane proteins all floated freely within the lipid layer of the membrane.
However, it has been shown that some proteins are immobile, held in place by cytoskeleton proteins.
Restriction of protein movement allows membrane polarity, which can be seen in transporting epithelia.
Other proteins are mobile and move under the direction of cytoskeleton. For example, rhodopsin, the
protein pigment that absorbs light in the retina, rotates in place, somersaulting at a rate of 60° every 10
seconds.
3. Glycoproteins
As mentioned above, the prefix glyco means ‘glucose’, so a glycoprotein is a small amount of a
carbohydrate (sugar) attached to a large amount of protein. If the molecule is called a proteoglycan, then
there is more sugar (glyco) than protein. Glycoproteins are also found on the external surface of the
plasma membrane and act as a cell markers.
Function of Plasma Membrane Proteins
The proteins that are associated with the plasma membrane have an expansive range of roles.
1. Structural Elements
2. Cell Adhesion Molecules
3. Enzymes
4. Receptors
5. Transporters
1. Structural Proteins – Theses link cytoskeleton and membrane to maintain cell shape, e.g., microvilli,
red blood cells. The characteristic shape of the red blood cell is due to an extensive cytoskeleton that pulls
the cell membrane into a biconcave disc shape. In diseases such as hereditary spherocytosis, defects in
cytoskeletal proteins produce abnormally shaped red blood cells that are unable to move normally through
the circulatory system.
2. Cell Adhesion Molecules - Form part of the cell-to-cell connections holding tissues together.
Membrane-spanning proteins link the cytoskeleton to the extracellular matrix. The most common fibrous
protein that attaches a cell to adjacent cells is collagen!
3. Enzymes – Membrane associated enzymes act as any other enzymes do but are fixed to the plasma
membrane. Chemical reactions can take place on either membrane face, i.e. on the extracellular or
intracellular surface. For example, enzymes on luminal surface in small intestine cells (extracellular)
digest peptides and carbohydrates. Enzymes on the intracellular surface, such as adenylyl cyclase, play an
important role in signal transduction.
4. Receptors – These act as receivers for the body's chemical signaling system, with each receptor being
specific for a certain type or family of signal molecule. A ligand is any molecule binding to a receptor.
Ligand binding usually triggers another membrane event, this can be signal transduction (e.g., hormone
binding) or directly lead to an ion channel opening or closing (ionotropic effect).
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5. Transporters - Many molecules require the use of transporters to cross cell membranes. Most
lipophobic (can also be termed hydrophilic) molecules, such as smaller carbohydrates, amino acids,
peptides, proteins, and charged particles such as ions, must have assistance from membrane proteins in
order to get into or out of cells.
All of the above listed functions of plasma membrane proteins are very important. In the next stage that
follows, however, we are going concentrate on the role of plasma membrane proteins as transporters in
the body and the various mechanisms by which they move molecules from one side of the plasma
membrane to the other.
There are 2 Categories of Protein Transporters: Protein Channels and Protein Carriers
Protein Channels
Protein channels are well named; they are much like little water-filled channels, forming a passageway
that directly links the ECF to ICF. The narrow diameter of protein channels restricts passage through them
to small sized molecules, mostly water (H2O) and ions (K+, Na+, Cl- and Ca2+). Electrical charges lining
the inner channel may restrict the movement of some molecules; therefore they can be very specific as to
what they allow to travel through them. This mode of transport is very fast, much faster than protein
carriers because there is no need for the binding of the substrate as in protein carriers.
ECF
ICF
Will this get through?
Yes, it is small enough.
protein
channel
Will this get through?
No, it is too big.
plasma
membrane
Open channels spend most time in the open configuration and are also called pores. Other channels are
gated and spend most time in a closed state.
Three Types of Gated Ion Channels:
The protein channels that have gates that can open or close are called gated ion channels. There are three
types of gated channels that we will explore, and they differ in the ‘trigger’ that opens or closes the gate,
they are:
1. Chemically Gated Channels: triggered by specific ligands (chemicals) to open or close channel.
2. Voltage-Gated Channels: triggered by electrical changes across cell to open or close channel.
3. Mechanically Gated Channels: triggered by distention or physical force to open or close channel.
Some gated channels remain open and the molecules leak across the channel, these are often called "leaky
channels". The normal permeability of cells to Na+ and K+ is due to such leak channels.
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Protein Carriers
The second type of protein transporters are called protein carriers. These never form a direct or
continuous passage between the ECF and the ICF. They have a binding site (like enzymes) and will only
transport specific molecules that match this site. Once the molecule binds to the site, the protein carrier
undergoes a conformation (shape) change. It can rotate, or close one end while it opens the opposite, thus
carrying the molecule across membrane. This mode of transportation is slower than protein channels, as
they need to bind the substrate and change shape while moving substrates.
ECF
ICF
Will this get through?
Protein
carrier
Yes, it has the right shape for binding site.
Typically, carriers are used for transporting larger, polar molecules.
A perfect example is glucose. Glucose has a MW of 180, so it is a
larger molecule, but not massive like starch or albumin. It is also a
polar molecule, meaning it is soluble (mixes) in water. Amino acids
are another good example of molecules moved by carriers.
Properties of Protein Carrier Mediated Transport
Because of the way that protein carriers work, their transport exhibits saturation, specificity, and
competition.
Specificity
Protein carriers move only one type or family of closely related molecules. For example, GLUT
transporters move glucose, mannose, galactose, and fructose across membranes. They are specific for
naturally occurring 6-carbon monosaccharides. Other carriers will transport amino acids, and there can be
up to 20 different types of carriers, each specific for the 20 different amino acids the human body uses.
Competition
Carriers have preference (or affinity) for certain molecule(s). This can result in competition for the
binding site between various molecules. For example, maltose is a disaccharide made of 2 glucose
molecules, so one end of the maltose could try to occupy the binding site for a glucose transporter.
Although it can bind, typically it will not be transported in the process, it is not the right shape overall.
Thus in this case, maltose would be a competitive inhibitor for glucose transport.
Saturation
Saturation occurs when a group of protein carriers are transporting the substrate at its maximum rate, with
all carriers occupied. Saturation will depend on the number of available carriers and substrate
concentration. Cells can sometimes increase or decrease the number of available carriers to control
substrate movement. As the substrate concentration increases, transport rate increases until the carriers
become saturated. At this stage they are at their maximum transport capacity and cannot move things
across the membrane any faster.
An interesting consequence of saturation can be seen in the transport of glucose in the kidney. Normally,
you should not find any glucose in your urine. If you do, it can be a sign of diabetes mellitus. However, if
you were to consume large quantities of glucose, say by eating too many chocolates from your valentine
gift, you may have glucose in your urine that is not due to a disease state (not yet anyway!). The glucose
carriers in your kidney tubules can become saturated due to the abnormally high amounts of glucose being
filtered by your renal system. If the carriers reach their maximum and more glucose is still in the filtrate,
it will end up in the urine due to protein carrier saturation.
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MOVEMENT ACROSS MEMBRANES
You may have heard plasma membranes described as selectively or semi-permeable membranes. This
means that some molecules can get across and some molecules cannot. The membrane composition
determines which molecules move across. Permeable molecules can cross membrane by any method.
Impermeable molecules cannot cross cell membrane.
General Factors Influencing Molecule Permeability
Although the components of a plasma membrane can vary, the properties of a given molecule will have a
large effect on whether is passes through the plasma membrane easily, or if it needs assistance or if it
cannot pass at all.
1. Size of molecule – smaller molecules can more easily pass through than larger.
2. Polarity or lipid solubility of molecule – lipid soluble molecules pass through more easily than polar.
3. Charge of molecule – uncharged molecules pass through more easily than charged.
The permeability of a molecule can be influenced by all three of these factors, not just one. For example,
water (H2O) is a polar molecule, that is, it is insoluble (does not mix) in lipids. This would tend to make it
less permeable, since the phospholipid bilayer creates a significant barrier to polar substances crossing the
membrane. However, the molecular weight (MW) of H2O is only 18, thus it is very small and for this
reason can easily pass through most cell membranes in the human body.
Ions are commonly very small, but they are charged particles and cannot pass directly through membrane
by simple diffusion, they would require a protein channel, they would require a protein channel. At the
other end of the spectrum, just because a molecule is fairly large does not mean it cannot pass directly
through membrane by simple diffusion; relatively larger lipophilic substances can cross directly through
membrane by simple diffusion, as the lipid bilayer is not a barrier. Very large molecules or a large amount
of substance will typically require membrane transportation in a vesicle (see below).
There are 2 ways a molecule can transported across a cell membrane: Passive & Active
1. Passive Transport: does not require energy (ATP). Movement down a gradient.
1) Diffusion
2) Facilitated diffusion
3) Filtration
1) Diffusion
Diffusion is the net movement of molecules from an area of higher concentration to an area of lower
concentration. In other words, the molecule is moving down its concentration gradient. This is a passive
transport mechanism. Getting in a kayak and going down stream with the river is an example of passive
transport. No energy expenditure is required; you can just sit there and be moved down stream. In the
body, the net movement of molecules continues down its gradient until equilibrium is reached. Diffusion
can occur in open regions or across a partition such as a membrane.
Factors that Effect the Rate of Diffusion
Diffusion is a very common and important mode of transport in the human body. The oxygen (O2) that
enters our blood stream from our lungs does so by simple diffusion. A very important issue in human
physiology is what factors affect the rate of diffusion of a molecule from one side of a plasma membrane
to the other. Listed below are some of the important factors that affect the rate (how quickly) diffusion
takes place.
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Some factors that effect the rate of diffusion:
a. Size of the molecule (as indicated by its MW) – smaller = faster
b. Distance – shorter = faster
c. Temperature – warmer = faster
d. Surface area of membrane – greater = faster
e. Thickness of barrier – thinner = faster
f. Steepness of concentration gradient – greater = faster
As we continue in physiology, all of these factors will be revisited in the various organ systems.
2) Facilitated Diffusion
Some molecules that are polar or too big to use simple diffusion to get across a membrane can use protein
carriers to move down their concentration gradient. This requires no energy. The molecules must bind to
the membrane carrier (as discussed above), so in this way in needs the ‘help’ of a carrier to move down its
gradient across the membrane. As long as it is going down its concentration gradient, it is still diffusion.
The term ‘facilitated’ indicates that the molecule is getting some assistance. As we have seen, this process
is also prone to specificity, competition and saturation.
3) Filtration
Filtration is the net movement of water and solutes across a membrane due to the force of hydrostatic
pressure. Hydrostatic pressure can be defined as the force of a fluid on the walls of its container. It can
also be described as the force of gravity on a fluid. For example, if you place ground coffee on a paper
filter and pour water over the top of it, the filter allows water and small solutes to pass through, but not
the bigger coffee grinds. What you get on the other side is a filtrate of what was above, that is, anything
small enough to pass through the holes of the filter, thus the term ‘filtration’. In the human body, the
hydrostatic pressure of blood in a blood vessel pushes water and solutes across the blood vessel wall and
into the interstitium. This is a normal function of certain blood vessels, as we shall see later!
2. Active Transport: requires energy input (ATP)
1) Primary (direct) active
2) Secondary (indirect) active
3) Vesicular transport
Active transport requires the input of energy from ATP. This ATP id required because molecules are
being moved up or against their concentration gradients. It is proteins that move these molecules
against their concentration gradients. It is important to realize that creating and maintaining
disequilibrium across a membrane in the body is very important and useful. Again, this requires the input
of energy from ATP. The movement can be of one or more substances across a membrane:
1. Uniport: When a protein moves only one (uni) kind of molecule.
2. Co-transport: When a protein moves more than one molecule at a time.
a. Symport: Moves molecules in the same direction.
b. Antiport: Moves molecules in the opposite directions.
1) Primary Active Transport (direct)
In primary active transport, energy from ATP is directly used to transport molecules against their
concentration gradient. For example, the Na+/K+-ATPase is a membrane spanning protein carrier. Please
note the –ase ending, so it is also an enzyme that hydrolyzes (breaks bonds with water) ATP to get its
energy. It is also referred to as the 'Na+/K+ pump'. This is because it acts much like a pump that is bailing
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+
out a leaky ship. It works non-stop to continuously expel 3 Na ions out of the cell and at the same time
import 2 K+ ions into the cell per cycle. Each cycle of the pump requires 1 ATP molecule. Both Na+ and
K+ are being moved against their concentration gradients, therefore we know that ATP must be required
because this is active transport. The ATP is hydrolyzed to ADP + Pi + Energy! This is an antiport
mechanism, as both molecules are being transported in opposite directions. The Na+/K+ pump helps to
maintain the resting membrane potential (RMP) across the plasma membrane of all living cells. Draw a
diagram of the Na+/K+ pump.
2) Secondary active transport (indirect)
In secondary active transport, the ATP is used indirectly to move molecules across membranes.
Essentially what this means is the potential energy that is stored in a concentration gradient is used to help
move molecules across a membrane. An excellent illustration of how this is done is seen in the
Na+/glucose transporter. The relative concentration of Na+ is low on the inside, high on the outside of the
cell. When Na+ moves down its concentration gradient (into the cell) this force is harnessed to move
glucose against its concentration gradient (also into the cell). While the Na+ goes down its gradient, the
glucose can be dragged along with it, up hill, so to speak. The original source of ATP that allows this to
occur is the one used in the Na+/K+ pump described above, as it maintains a low Na+ concentration inside
the cell. This is a symport mechanism, as both molecules are being transported in the same direction.
Draw a diagram of the Na+/glucose transporter.
3) Vesicular Transport
Vesicular transport is used to move large macromolecules or large quantities of a molecule across the
plasma membrane. Vesicles are like mini lipid bilayer bubbles that bud off from plasma membrane and
encapsulate large molecules. This is an active form of transport that directly requires energy in the form of
ATP for the maneuvering of the cytoskeleton.
There are two main forms of Vesicular transport
1. Endocytosis - bringing material into the cell, inward vesicular transport.
2. Exocytosis - releasing material from the cell, outward vesicular transport.
1. Endocytosis: There are three general kinds of endocytosis.
1) Pinocytosis (cell drinking): relatively unselective whereby ECF is transported into the cell.
2) Phagocytosis is a process by which cells engulf a particle or another cell into a much larger
vesicle, e.g., certain types of WBC (called Macrophages) engulf bacteria this way.
3) Receptor-Mediated Endocytosis: This is a very selective process. Receptors on the external
surface of the plasma membrane bind specific ligands. This ligand-receptor complex then creates a
clathrin-coated pit, a type of invagination of the membrane. The membrane then pinches this off as
cytoplasmic vesicle, thereby ingesting the ligand-receptor complexes. The vesicle membrane and
the receptors are recycled to the surface membrane to be used again.
2. Exocytosis: This is used by many cells to secrete or release large molecules or large amounts of a
molecule. Intracellular vesicles fuse with the plasma membrane, then releases its contents into ECF. This
process requires energy and Ca2+ and involves other proteins. An excellent example of how this is
commonly used in the body is the release of neurotransmitters from neurons into the synaptic cleft. This
process is also used to secrete large lipophobic molecules, such as hormones, protein fibers and mucus
across cell membranes. Exocytosis is also used to insert proteins, such as receptors, into membrane.
9
Lysosomes can remove waste in this manner and is often regulated from outside of the cell (e.g.,
hormone-induced hormone release).
Transcytosis and Vesicular Transport
Transcytosis means movement across (trans) a cell (cytosis); it can involve endocytosis, then vesicular
transport across cell, then exocytosis out of the cell at the other end. So the substance has moved
completely across the cell. This provides for movement of large proteins intact, e.g., the absorption of
maternal antibodies through breast milk, or the movement of proteins across capillary endothelium.
Transport Across Epithelial Linings
An excellent summary of the various types of transport discussed so far is the transport of molecules
across epithelial linings, called transepithelial movement. Epithelial membranes are polarized with an
apical (lumen or top side) and basolateral (ECF side) membranes have different proteins. The Na+-glucose
symport on apical membrane and the Na+-K+-ATPase is only on basolateral (bottom side) membrane.
Transporting epithelial cells can alter their permeability by inserting or withdrawing membrane proteins.
Although glucose is a large polar molecule (and thus has 2 strikes against it for having an easy passage
across a membrane), there are two different transport systems to move glucose across epithelial cells:
1. Secondary active transport. The Na+/glucose symport from the lumen of the gut into the cell through
the apical membrane. This is made possible by the continuous active transport of Na+, constantly being
ejected across the basolateral membrane of the cell via Na+-K+-ATPase.
2. Glucose can also move across a membrane down its concentration gradient by facilitated diffusion, as
seen in across basolateral membrane of the cell.
As an interesting note, the substance ouabain, a known powerful toxin to cells, specifically inhibits the
Na+/K+-ATPase. These Na+/K+ pumps are found only on the basolateral membrane of transporting
epithelial cells. Ouabain placed on one side of the epithelium affects only that side, so only when ouabain
is applied to the basolateral side will cause glucose transport to decrease slowly, as the Na+ gradient is
abolished, because Na+ enters the apical side with glucose but is not pumped out, so over time the Na+
gradient that powers the symporter disappears.
BODY FLUID COMPARTMENTS
Fluid in the body can be described as being in one of three different compartments: 1) Intracellular; 2)
Interstitial; and 3) Plasma.
1. Intracellular fluid (ICF): the fluid inside cells (within the plasma membrane).
2. Interstitial fluid: the fluid directly bathing cells (tissue fluid); lacks plasma proteins.
3. Plasma: the fluid portion of blood, it can also be referred to as vascular volume.
Extracellular
Fluid (ECF)
The term extracellular fluid (ECF) simply means the fluid outside of a cell. So you can see that both
interstitial fluid and plasma are considered to be ECF. In a healthy human body, all of these fluids must
have an osmolarity within the range of 295 to 310 mOsM. However, they differ dramatically in the
relative concentrations of important ions and molecules.
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Table 1. A comparison of the relative concentrations in the three tissue compartment volumes.
Ion/Molecule
K+
Na+
ClCa2+
Proteins
Plasma
Interstitial fluid
↓
↑
↑
↑
↑↑
↓
↑
↑
↑
↓↓
Intracellular
↑
↓
↓
↓*
↑
* In muscle cells, calcium ions (Ca2+) are stored intracellularly in the sarcoplasmic reticulum (SR).
Distribution of Water and Solutes in the Body
Living cells use energy to maintain a state of chemical and electrical disequilibrium across the cell
membrane. Cell membranes and capillary endothelium act as selective barriers establishing a solute
disequilibrium. What this means is that there are very different concentrations of certain ions on the
outside of the cell compared to the inside, as seen in Table 1 above. These differences are maintained by
active transporters which move solutes against their concentration gradients constantly, leading to
chemical and electrical disequilibrium (un-evenness). Because things are being moved up or against their
gradients, maintaining this disequilibrium requires energy input in the form of ATP.
The Distribution Water in the Body
Intracellular fluids = 2/3 of body's water
Extracellular fluids = 1/3 of body's water
Plasma = 8% ECF
Interstitial fluid = 25% ECF
Osmosis
Osmosis is the net movement of water across a semipermeable membrane from a higher water
concentration to a lower water concentration. Typically, water moves freely until osmotic equilibrium is
reached. Quite simply, osmosis is a special case of diffusion for water.
Osmolarity
Osmolarity describes the number of particles per liter of a solution, Osmoles per liter = Osmol/L or OsM
or milliosmoles (mOsM). Osmolarity takes into account dissociation of molecules in solution and
converts molarity to osmolarity. Osmolarity (osmol/L) = molarity x (number of particles in solution).
Osmolarity depends solely on the number of particles per liter of solution. In the human body, all fluid
compartment volumes have an osmolarity that falls within the narrow range of 295 to 310 mOsMs. We
already know that the fluid in these three compartments is different, but in a health body, their
osmolarities must be within this range.
Tonicity
The tonicity of a solution is a measure of its strength, like the strength of a muscle can be referred to as its
‘tone’ or tension. A solution is made up of two components; the solvent (water in physiology); and the
solute (whatever is dissolved in the water). By definition, the solvent is more abundant than the solute and
the relative concentration of the solute will determine the tonicity of a fluid. The tonicity of a fluid
determines how the volume of a cell will change if placed in that solution. Tonicity has no units, it is
always comparative.
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In human physiology, tonicity is matched with osmolarity in such a way that the optimal value range for
human cells (295 to 310 mOsM) is termed isotonic. The prefix iso- means “same”. If we have three
beakers, each with the following solutions in them, we need to ask ourselves how a normal cell would
respond to each environment. The way we can answer this is to decide which direction water would move
(into or out of the cell)
1. Isotonic solution: The cell’s intracellular fluid has the same osmolarity
as the fluid surrounding it in the beaker, so there is no net movement of
H2O into or out of the cell and its volume doesn't change. This is what cells
like and how they function best.
Solvent – water.
Solute – particle in solution.
Cell in solution.
2. Hypertonic solution: This solution is too strong (hyper = above), having
more solutes in solution than the intracellular fluid of the cell. Water is in
higher concentration inside the cell and will move down its concentration
gradient (via osmosis) into the beaker, where water is less. The cell’s volume
decreases or shrinks, this is called crenation. When cells crenate, they loose
function, which is not good for the body.
3. Hypotonic solution: This solution is too weak (hypo = below), having
fewer solutes in solution than the intracellular fluid of the cell. Water is in
higher concentration inside the beaker and will move down its concentration
gradient (via osmosis) into the cell, where water is less. The cell’s volume
increases and may even burst (cell lysis). When cells expand, they loose
function, which is not good for the body.
In a more complex analysis, tonicity depends on the nature of the solutes, not on osmolarity. Penetrating
solutes can enter a cell (e.g., glucose and urea) and non-penetrating solutes cannot enter a cell (e.g.,
sucrose, NaCl). NaCl is considered to be functionally non-penetrating, as it gets pumped out of the cell as
soon as it enters. We will discuss the issues of tonicity and osmolarity more fully in lab.
The Body is in a State of Electrical and Chemical Disequilibrium
This is the result of the chemical disequilibrium. The major intracellular ions are K+, phosphate (and to
some degree proteins). The extracellular ions are Na+, Cl-. The differences between the two sides of the
plasma membrane create the electrical disequilibrium and the Resting Membrane Potential (RMP).
Electricity and Electrical Signals
Atoms are electrically neutral. Ions are created as electrons are added/removed and for each cation in the
body, there is a matching anion somewhere. There are important principles to remember for electricity in
physiological systems. The Law of Conservation of Electric Charges means that the net amount of electric
charge produced in any process is zero. Opposite charges attract, like charges repel and energy is required
to separate opposite charges or bring together like charges. Conductors of electrical charge allow free
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movement of positive and negative charges whereas insulators prevent movement of charged particles as
it turns out, cell membranes are insulators.
The Plasma Membrane is an Insulator
Separation of electrical charges in body occurs across the cell membranes. Ions have electrical and
chemical concentration gradients across the plasma membrane. The Na+, Cl- and Ca2+ concentrations are
higher in the extracellular fluid and the K+ concentration is higher inside the cell. These electrical and
chemical gradients, combined is referred to as the Electrochemical Gradient, are created by active
transport mechanisms and selective membrane permeability to certain ions. The inside of cell is negative
relative to the outside at rest and a voltmeter is used to measure the membrane potential difference.
The next section of physiology, neurophysiology, will further examine this dynamic relationship across
the plasma membrane in neurons.