Membrane Transport

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ICF vs. ECF

The cell membrane is a highly selective barrier
separating the ICF from the ECF.

MOLECULES

At any temperature above absolute zero, molecules are
constantly in motion. Molecular motion increases with
temperature, and we experience this motion as HEAT.

Molecules are constantly colliding with other molecules
and thereby changing direction. The net movement
is essentially random.

The number of collisions per unit time is dependent upon
the velocity (which in turn varies with molecular size
and temperature) and also, very importantly, on the concentration
of the molecules (i.e. the number per unit volume).

DIFFUSION

Although molecules move in all directions, everything else
being equal, there will be a net movement
(i.e. a NET FLUX) of molecules from a region of higher
concentration to a region of lower concentration.

Physiologically important diffusion processes take place only
over very short distances (normally a fraction of a mm).

[see Figures 4-1a,b; 4-3, 4-2]

[Fig. 4-4: The diffusion of substance X into a cell. Note that
the rate of diffusion (i.e. the change in ICF concentration
per unit time) is dependent upon the concentration gradient.
Diffusion is rapid initially, but declines towards zero
as equilibrium is approached.

Diffusion time (t) increases with the square of diffusion distance

t is proportional to R squared

[see Table of diffusion times]

[see Figure of steady state diffusion across a membrane

FICK EQUATION: dQ = -D A (dc/dx) dt

where D = the diffusion coefficient, A = the area of diffusion
and t = time

In the Fick Equation, Q represents the quantity of
a substance diffused

We can simplify this relationship by using proportions

Q is proportional to A * t * delta c/x

This proportionality reveals that Q is directly proportional
to exposed surface area (A), elapsed time (t), and the
concentration gradient (delta c), and that Q is inversely
proportional to the diffusion distance (i.e. membrane
thickness, x).

Diffusion does not require a membrane and can take place
in gases, liquids, and even solids. The rate of diffusion,
however, is dependent upon the medium. Diffusion can be very
rapid in gases, is much slower in liquids, and is slower yet in solids.

Example: (the diffusion of oxygen at 20 C)
The rate of diffusion in water is 2.4 times that in skeletal muscle
The rate of diffusion in air is 786,000 times that in skeletal muscle

OSMOSIS

Osmosis (a special case of diffusion) represents the diffusion of
WATER across a selectively (or differentially) permeable membrane.

There is an inverse relationship between the concentration of the
water (= the solvent) and the concentration of substances (= solutes)
dissolved in the water.

There will be a net flux of water from a region of higher water
(lower solute) concentration to a region of lower water (higher
solute) concentration.

With respect to osmosis, solute concentrations are typically
expressed in terms of Osmoles (or milliosmoles)

For a nonelectrolyte (such as glucose) 1 Osmole = 1 Mole
= the molecular weight in grams

As you will recall,
a one molar solution = one mole plus enough water to form
one liter of solution
a one molal solution = one mole plus 1000 g of water

A one molal solution is slightly more dilute than a one molar
solution; however, for physiological purposes, the distinction
is not very important.

Osmosis depends upon the number of osmotically active particles
in solution. For a nonelectrolyte, one molecule is equivalent to
one particle. Therefore, one mole = one osmole.

However, electrolytes dissociate in water (i.e. one molecule may
form two or more particles). NaCl is a strong electrolyte and
dissociates almost (but not quite) completely into sodium ions
and chloride ions. Therefore, a one molar solution of NaCl
is almost 2 osmolar.

The blood plasma of most mammals (including humans) is a
mixture of solutes (mostly electrolytes) yielding an osmotic
concentration of about 0.30 Osm (or 300 mOsm).

Physiological saline (i.e. a salt solution having the same
osmotic concentration as mammalian plasma) = 0.9 % NaCl

NOTE: 0.9% NaCl = 9 g NaCl/liter
The molecular weight of NaCl = 58.5
Therefore, 0.9 % NaCl = 9/58.5 = 0.154 M
Assuming nearly complete dissociation, this equates to
an osmotic concentration of about 0.30 Osm

[see Fig. 4-19]

[see Animation]

[see Fig. 4-18]

[see Figure comparing penetrating and non penetrating solutes]

Although diffusion is classically defined as a net movement of
molecules from a region of higher concentration to a region of
lower concentration, the molecules do NOT move because of
the concentration gradient per se.

Diffusion actually reflects the net movement of molecules from
a region of higher towards a region of lower FREE ENERGY.

In the case of osmosis, we are dealing with the free energy
of the water molecules in the solution (i.e. with the WATER ACTIVITY).

Free energy increases as concentration increases.

It is important to note, however, that free energy is also affected
by other factors, such as temperature and applied external pressure.

For example: If we have an equal concentration of penetrating
molecules, but the solutions on the two sides of a membrane
are at different temperatures, there will be a net flux of solute
molecules from the warmer towards the cooler side.

COLLIGATIVE PROPERTIES

These properties depend only on the number of particles in solution,
irrespective of their chemical nature.

An increase in [solute] is associated with:
a. an increase in osmotic pressure
b. a decrease in vapor pressure
c. an increase in the boiling point
d. a decrease in the freezing point

Knowing any one colligative property, we can calculate any other.

In a thermodynamic sense, the colligative properties of a solution
depend on the free energy of the water molecules (i.e. on the
"water activity").

Dilute solutions behave like gases. We can therefore apply
the ideal gas law:

PV=nRT

where P = pressure, V = volume, n = the number of molecules,
R = the gas constant, and T = temperature.

We can rearrange the equation (by dividing both sides by V)
to obtain:

P = (n/V)RT

We can now substitute osmotic pressure (which we can symbolize)
by pi) for P, and osmotic concentration (C) for (n/V)

We then obtain the relationship:

pi = CRT

R is a constant. This equation thus reveals that the osmotic pressure
exerted by a solution is proportional to the product of the osmotic
concentration times the absolute temperature.

Most commercial instruments for monitoring osmotic concentration
measure either vapor pressure or freezing point depression.

FREEZING POINT METHOD:

A one osmolar solution freezes at -1.86 C. Therefore, delta fp
(the change in freezing point) = 1.86 C

Rearranging: C = delta fp/1.86

[see figure depicting evolutionary transitions]

Marine invertebrates - most are isosmotic
Freshwater animals - all are in a hyposmotic environment
Marine bony fishes - all are in a hyperosmotic environment

Some animals (especially those living in estuaries) are exposed to
drastic changes in their osmotic environment.

[see figure of osmoregulators and conformers]

As noted earlier, there is an inverse relationship between
pressure and volume:

PV = nRT Therefore, P = (nRT)/V

P is proportional to 1/V

Therefore, osmotic pressure is proportional to 1/V

where V = cell or body volume

For osmoregulators, internal osmotic concentration is constant.
They therefore tend to also regulate body volume (i.e. they are
volume regulators.

Osmoconformers, in contrast, are often volume conformers.

Although osmoconformers are often volume conformers, a rigid
carapace or external covering can help to prevent or mimimize
body volume changes.

Also, some osmoconformers can regulate volume by adding or
dumping solute (e.g. amino acids).

[see Figure]

In a hyposmotic environment, animals may either osmoregulate
(e.g. by excreting water) or conform. If they conform, they may
either volume conform or volume regulate. In any event, even if they
do not osmo- or volume regulate, they will regulate ions.

The plasma membrane is SELECTIVELY PERMEABLE. Some
substances penetrate rapidly, others more slowly or not at all.

For a given set of conditions, we can define a permeability constant
(Kp) for a membrane such that the net flux (F) across that membrane
equals Kp times the concentration gradient (delta C).

F = Kp delta C

We can make some generalizations about the permeability of cell membranes
to various substances:

(a) Small molecules enter more rapidly than do larger molecules.

[see Figure]

(b)Lipid-soluble (e.g. nonpolar) molecules penetrate more rapidly than do
lipid insoluble substances.

[see Figure] Note: The partition coefficient (solubililty in oil/solubility
in water) is a measure of lipid solubility

(c) Non-charged molecules penetrate more rapidly than do charged substances

However, membranes contain protein channels (some of which are
gated) which allow selected ions (e.g. Na+, K+, Cl-, Ca2+) to enter very rapidly

[Fig. 4-7]

Some ion channels are always open. Other channels are sometimes open
and sometimes closed (i.e. they are "gated")

Gated channels may open in response to:
(a) a mechanical change
(b) an electrical (i.e. voltage) change
(c) a chemical change

MEDIATED TRANSPORT

Some substances penetrate membranes faster than we would expect
them to (based on their chemical nature) or even move in a direction
opposite to that expected for diffusion.

Glucose, for example, is a fairly large polar molecule with a low
lipid solubility. We would expect it to diffuse into cells only very slowly,
but, in fact, it enters many cells quite rapidly.

Specific carrier proteins (i.e. transporters) on the plasma
membrane appear to be "helping" glucose across the membrane
barrier. This is a type of mediated transport referred to as
FACILITATED DIFFUSION. Note that the direction of movement is
that expected for simple diffusion.

[Fig. 4-8] This is a general model for mediated transport.
It could, for example, represent facilitated diffusion from
the ECF to the ICF.

Mediated transport systems have certain properties
(i.e. specificity, saturation, and competition) which distinguish
them from simple diffusion.

(a) Specificity

Mediated transport systems tend to be specific for a particular chemical,
or, at most, a group of related chemicals.

The system which transports glucose will not transport amino acids and vice versa.

(b) Saturation

There are a finite number of specific carrier proteins, and the system can
become saturated once all are functioning at maximum capacity.
[see Fig. 4-9]

(c) Competition

All substances diffuse independently; however, closely related molecules
may compete for a limited number of carrier proteins.
[see Figure]

ACTIVE TRANSPORT

Cells can spend energy (in the form of ATP) to move molecules against their
concentration gradient (i.e. from a region of lower concentration to a region of
higher concentration). This is a constant, and very essential, activity of living cells.
As much as 25% of a cell's total energy expenditure may be used for active transport.

Some, but by no means all, active transport systems are "coupled" (i.e. they move
two or more different substances in the same or different directions.

If the molecules are moved in the same direction, the process is termed SYMPORT.
If in the opposite direction, it is called ANTIPORT.

The sodium/potassium ATPase system is an important example of an antiport coupled
pump (trading 3 sodium ions for 2 potassium ions).

[Fig. 4-11] This is a model of a generalized primary active transport system.

[see Animation]

[Fig. 4-12]

[Fig. 4-13] Secondary active transport systems are coupled systems which use
the energy associated with an ion gradient to move other molecules "uphill".
The actual expenditure of ATP is indirect (needed to maintain the ion gradient).

[see Animation]

[Fig. 4-14] These are both examples of secondary active transport. The direction
of movement may be either symport (i.e. cotransport) or antiport (i.e. countertransport).

[Figure depicting transport of calcium]

[Fig. 4-15]

VESICULAR TRANSPORT

There are some special mechanisms whereby large molecules and other particles
can cross cell membranes.

(a) Phagocytosis ("cell eating")
(b) Endocytosis
(c) Exocytosis

NOTE: Some consider phagocytosis to be a special case of endocytosis. However,
most believe that phagocytosis is fundamentally different inasmuch as it involves
an evagination of the cell membrane, whereas endocytosis involves an invagination.

[see Figure]

[Fig. 4-20]

[see Figure] Endocytosis can be non-selective (= pinocytosis or fluid endocytosis)
or selective (absorptive or receptor-mediated endocytosis). Some use the term
'pinocytosis' for both processes.

BULK FLOW

As we have noted, diffusion is very rapid and effective over short distances,
but slow and ineffective over large distances. Bulk flow is an important alternative
mechanism for molecular movement. Bulk flow depends on a pressure difference
between two regions of a liquid or a gas. Bulk flow and diffusion are NOT
mutually exclusive.

Bulk flow is proportional to delta P

TRANSEPITHELIAL TRANSPORT

The movement of materials across epithelia may involve a variety of
active and passive mechanisms.

EPITHELIA

Epithelial cells are very important in physiology. They form the integument
(external lining of the body) and they line hollow structures such as blood vessels,
kidney tubules, and the intestine.

These cells are connected together and organized into layers by various
specialized membrane junctions.

[Fig. 3-10a,b]

[Fig. 4-22]

[Fig. 4-23]

[see Figure]

[Fig. 4-24]

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