Cell Membrane Transport
Cell Membrane Transport
Introduction
Cells need to exchange materials with their environment to support life.
Oxygen can permeate the phospholipid bilayer, but glucose cannot.
Membrane proteins assist in transporting specific molecules across the plasma membrane.
The compositions of intracellular fluid and extracellular fluid differ depending on the proteins present (Table 4.1).
This chapter focuses on basic cellular and molecular theories of membrane transport, crucial to understanding organ system physiology.
Factors Affecting the Direction of Transport
The energy difference in molecules on the two sides of the membrane determines the direction of spontaneous transport (passive transport) and the need for energy to move the molecule against the energy gradient (active transport).
Passive Transport Versus Active Transport
Transport of molecules across a membrane follows the same principles as chemical reactions: spontaneous (or passive) movement occurs from areas of high energy to areas of low energy; to move in the opposite direction requires an input of energy.
The energy of a solution depends on the solute concentration (and charge, if the solute is an ion); energy increases as solute concentration increases.
Solutes move passively from an area where they are in greater concentration to an area where they are in lesser concentration, or down their concentration gradient.
Transport of molecules across a membrane is called active transport if it requires energy, and passive transport if it does not.
Simple diffusion—the movement of a molecule into or out of the cell by its own thermal motion—is one form of passive transport, but certain forms of protein-mediated transport are also passive.
Active transport is always mediated by transport proteins referred to as pumps.
Driving Forces Acting on Molecules
Any difference in energy existing across a membrane acts as a driving force that tends to push molecules in one direction or another.
The direction of this force is always from higher to lower energy, which indicates the direction in which molecules will go if they are allowed to move spontaneously.
These driving forces can arise as a result of concentration differences or other factors that affect molecular energies.
Molecules are generally influenced by three types of driving forces: chemical, electrical, and electrochemical.
Chemical Driving Forces
When a substance is present in different concentrations on either side of a membrane, a concentration gradient is said to exist across the membrane.
We consider the term “concentration gradient” to be synonymous with the difference in concentration and give it the symbol ΔC.
When molecules are moving from higher to lower concentration, we can say that they are moving down a concentration gradient; movement in the opposite direction is up a concentration gradient.
Because molecules will move down a concentration gradient spontaneously, we can think of a concentration gradient as a kind of force that “pushes” molecules in that particular direction.
Thus we refer to a concentration gradient as a chemical driving force, the direction of which is always down the concentration gradient (Figure 4.1).
The rate at which a substance is transported varies with the size of the concentration gradient and generally increases as the size of the gradient increases.
The magnitude of the chemical driving force increases as ΔC increases.
When more than one substance is present, as is the case with real cells, more than one concentration gradient exists.
Any chemical driving force that might be acting on a given substance depends only on the concentration gradient of that particular substance.
Electrical Driving Forces
Molecules moving across membranes can be affected by factors other than the chemical driving force.
This is particularly true of ions, which are influenced by electrical driving forces in addition to chemical driving forces.
Electrical driving forces arise due to the membrane potential, a difference in electrical potential or voltage that exists across the membranes of most cells.
The existence of a membrane potential reflects an unequal distribution of positively charged ions and negatively charged ions across the plasma membrane.
The Membrane Potential
The fluids in the body contain a wide variety of solutes, including many ions (also called electrolytes)—that is, substances possessing an electrical charge.
Some ions are cations, which have a positive charge; others are anions, which have a negative charge.
Ions are also present in salt solutions, such as seawater, but we normally cannot detect the presence of the ions’ electrical charges because the number of positive charges matches the number of negative charges.
Such a solution is said to be electrically neutral because the positive and negative charges cancel out each other, giving a net (total) electrical charge of zero.
Likewise, the total electrical charge of your body is zero because the number of cations in your body equals the number of anions.
A person may pick up and emit charges, however, such as when you rub your feet on a carpet (pick up negative charge) and then touch a metal object or other conducting material to release this electrical charge.
In intracellular or extracellular fluid, cations and anions are present in unequal numbers; consequently, these fluids are not electrically neutral.
Intracellular fluid contains a slight excess of anions over cations, giving it a net negative charge.
Extracellular fluid contains a slight excess of cations over anions, giving it a net positive charge.
Because positive and negative charges are distributed unequally between the inside and outside of a cell, a separation of charge is said to exist across the membrane (Figure 4.2).
When charges are separated, a potential energy (voltage) exists.
The excess negative and positive charges of intracellular and extracellular fluid tend to be clustered close to the membrane because the excess negative charges on one side of the membrane are attracted to the excess positive charges on the other side.
A cell’s membrane potential reflects this separation of charge and is given in units of electrical potential—in millivolts (mV), which are 1/1000 of a volt.
The magnitude of the membrane potential (number of millivolts) depends on the degree of charge separation: The greater the difference in charge between the two sides of a membrane, the larger the membrane potential.
By convention, the sign of the membrane potential (positive or negative) is taken to be the sign of the net charge inside the cell relative to outside.
Because the inside of a cell is typically more negatively charged than the outside, the membrane potential is usually negative.
For many cells, the membrane potential, which is denoted by the symbol Vm, is approximately negative 70 millivolts (Vm = -70 mV).
How the Membrane Potential Creates an Electrical Driving Force That Acts on Ions
An electrical potential is a form of potential energy; that is, it is an electrical force acting on charged particles and has the potential to cause those particles to move.
For example, AA batteries separate 1.5 volts of charge across the two terminals. One terminal is positive, the other negative.
Should a switch be thrown to provide a connection between the two terminals, then charge will flow as an electrical current from one terminal to another.
If a light bulb is placed in between the terminals, then the current can be used to power the bulb.
The membrane potential works in a similar fashion. The separation of charge is a potential energy for current flow across the membrane.
Current in biological systems is caused by ion movement.
Thus the membrane potential creates an electrical driving force for the movement of ions.
To determine the direction of the electrical driving force, we need simply know the valence (or charge) of the ion, the sign of the membrane potential (usually negative), and this simple rule: Opposites attract, likes repel.
Thus cations are attracted by the negative charge inside the cell and have an inward-directed electrical driving force.
Anions, by contrast, are repelled by the negative membrane potential and have an outward-directed electrical driving force (Figure 4.3).
Uncharged molecules, such as glucose, are not affected by the membrane potential and, therefore, have an electrical driving force of zero.
The magnitude of the electrical driving force on an ion depends on the size of the membrane potential and the quantity of charge carried by the ion, and it increases as either of these factors gets larger (Figure 4.4).
A larger negative membrane potential, for instance, means a greater number of negative charges inside and positive charges outside, which increases the attractive and repulsive forces acting on an ion.
If an ion carries more charge, the attractive and repulsive forces are also increased, which makes the electrical driving force stronger.
Electrochemical Driving Forces
To determine whether ions are being transported passively or actively, a physiologist must identify all the driving forces that might be acting on them.
In general, when ions are transported across membranes, two driving forces are influential: (1) a chemical force reflecting the ions’ tendency to move down their concentration gradient (from higher to lower concentration) and (2) an electrical force reflecting the ions’ tendency to be pushed in one direction or the other by the membrane potential.
The total force acting on the ions is the combination of these chemical and electrical driving forces, referred to as the electrochemical driving force.
The direction of the electrochemical driving force acting on an ion depends on the net direction of the electrical and chemical driving forces.
If both forces go in the same direction, then the electrochemical driving force also acts in that direction.
Conversely, if the electrical and chemical forces go in opposite directions, then the electrochemical force acts in the direction of the larger force.
Determining the Direction of the Electrochemical Driving Force
To determine whether the electrical or chemical force is larger, a physiologist must know an ion’s equilibrium potential, a hypothetical value for the membrane potential at which the electrical driving force is equal and opposite to the chemical driving force, producing an electrochemical driving force of zero.
If the membrane potential equals the equilibrium potential for an ion, that ion will not move spontaneously in either direction because the total driving force acting on it is zero. In other words, the ion will be at equilibrium.
The magnitude and sign of an ion’s equilibrium potential depend on the size and direction of the ion’s concentration gradient, and on the ion’s valence.
Larger concentration gradients mean larger equilibrium potentials because a greater electrical force is required to equal or “balance” a larger chemical force.
The sign of the equilibrium potential is such that the electrical force goes in the direction opposite to the chemical force.
In the case of sodium ions (Na+), which are found in higher concentrations outside a cell, the chemical force is directed inward. Thus an outwardly directed electrical force is required to balance the chemical force.
Because Na+ is positively charged, a positive membrane potential will exert an outward electrical force that balances the inward chemical force. This means that the Na+ equilibrium potential must be positive.
If an ion’s concentration on either side of a membrane is known, its equilibrium potential can be calculated using the Nernst equation.
Determining the Direction of the Electrochemical Driving Force (Procedure)
Identify the directions of the chemical and electrical driving forces acting on the ion. If the two driving forces are going in the same direction, the electrochemical force also acts in that direction, and no further analysis is necessary.
If the chemical and electrical forces act in opposite directions, compare the sizes of the equilibrium potential and the membrane potential. If they are equal in magnitude, then the electrochemical force is zero and the ion is at equilibrium. If not, proceed to step 3.
If the equilibrium potential is larger in magnitude than the membrane potential, then the chemical force is larger than the electrical force; the electrochemical force, therefore, acts in the same direction as the chemical force. If the membrane potential is larger in magnitude than the equilibrium potential, then the electrical force is larger than the chemical force; the electrochemical force, therefore, acts in the same direction as the electrical force.
Application of this procedure is illustrated in Figure 4.5 for potassium ion (K+), whose intracellular and extracellular concentrations are 140 mM and 4 mM, respectively (see Table 4.1), giving an outwardly directed chemical force and an equilibrium potential of -94 mV (EK = -94 mV).
In all three panels in Figure 4.5, the membrane potential is negative, producing an inwardly directed electrical force that opposes the chemical force.
In Figure 4.5a, the membrane potential and the equilibrium potential are equal, giving an electrochemical force of zero.
In Figure 4.5b, the equilibrium potential is larger than the membrane potential (-70 mV), giving an electrochemical force that is directed out of the cell.
In Figure 4.5c, the membrane potential (-100 mV) is larger than the equilibrium potential, so the electrochemical force is directed into the cell.
Significance of the Electrochemical Driving Force
The electrochemical force is the total driving force acting on transported ions, determining the direction in which the ions move if they are allowed to cross the membrane spontaneously.
When ions are transported passively, they always move in the direction of the electrochemical driving force, meaning they move down their electrochemical gradient.
When ions are transported actively, they move in the direction opposite to the electrochemical force, or up their electrochemical gradient.
Rate of Transport
The rate of a metabolic reaction is important because reactions must proceed at a rate fast enough to meet the body’s metabolic demands.
For this to occur, molecules must be transported across membranes at sufficient rates.
The rate at which a substance is transported across a membrane refers to the number of molecules that cross the membrane in a given length of time, called the flux.
Flux is usually expressed in units of moles per second, or some equivalent.
When molecules are transported in one direction or the other (into or out of a cell), it refers to a net movement of molecules across the membrane.
Individual molecules actually move across a membrane in both directions, but more of them may move in one direction than in the other.
This bidirectional flow of molecules is illustrated in Figure 4.6, which depicts a membrane separating two solutions in a chamber.
In this example, molecules cross the membrane by simple diffusion under two conditions: (1) when their concentration is the same on both sides and (2) when the concentration on the left side is twice that on the right side.
Passive Transport
In passive transport, molecules move across the membrane down their chemical or electrochemical gradients. No energy is required.
Types of passive transport include simple diffusion, facilitated diffusion, and diffusion through ion channels.
Simple Diffusion: Passive Transport Through the Lipid Bilayer
Simple diffusion is the least complicated of all transport mechanisms.
The movement of molecules from one location to another simply as a result of their own thermal motion is called diffusion.
Thermal motion is often called random thermal motion because individual molecules move helter-skelter in many different directions because of collisions with other molecules.
If thermal motion is random, then how is it that diffusing molecules always move down their concentration gradient? The answer lies in the distinction between individual molecules, which move randomly, and a population of molecules, which always moves down its concentration gradient.
Factors Affecting Rates of Simple Diffusion
When a substance is transported passively across a membrane by simple diffusion, the rate at which it is transported depends on three factors: the magnitude of the driving force, the membrane surface area, and the permeability of the membrane.
The magnitude of the driving force: In simple diffusion, the rate of transport is directly related to the size of the driving force.
Membrane surface area: The rate at which molecules are transported across a membrane varies in direct proportion to the membrane’s surface area.
Membrane permeability: The permeability of a membrane to a particular substance depends on both the nature of the transported substance and the properties of the membrane that influence the ease with which molecules are able to penetrate it.
Facilitated Diffusion: Passive Transport Utilizing Membrane Proteins
Some substances that are transported passively do not cross membranes by simple diffusion but instead cross by way of transport proteins in the membrane—a process known as mediated transport.
Facilitated diffusion distinguishes passive mediated transport from simple diffusion and from active transport.
A carrier is a transmembrane protein that binds molecules on one side of a membrane and transports them to the other side by means of a conformational change.
The net flux of facilitated diffusion depends on the frequency of solute binding to the carrier molecule on the two sides of the membrane.
Factors Affecting the Rate of Facilitated Diffusion
The rate of facilitated diffusion is determined by three factors: the transport rates of the individual carriers, the number of carriers in the membrane, and the magnitude of the concentration (or electrochemical) gradient of the transported substance.
Diffusion Through Channels
A channel is a transmembrane protein that transports molecules via a passageway or pore that extends from one side of the membrane to the other.
Common channel types include water channels (aquaporins) and ion channels.
The mechanism of transport through an ion channel depends on the type of channel.
Factors Affecting the Rate of Transport Through Ion Channels
The rate of ion movement through channels depends on the transport rate of individual channels and the number of channels in the membrane.
Ion channels can exist in two conformations: a closed state and an open state.
Active Transport
Active transport requires energy, whereas passive transport does not.
The two basic forms of active transport—primary and secondary active transport—differ in the nature of the energy source expended.
Primary active transport uses ATP or some other chemical energy source directly to transport substances.
Secondary active transport is powered by a concentration gradient or an electrochemical gradient that was previously created by primary active transport.
Primary Active Transport
The membrane proteins that perform primary active transport function both as transport proteins and as enzymes.
The sodium-potassium pump (Na+/K+ pump or Na+/K+ ATPase) is present in nearly every cell and is crucial to several important physiological processes.
The Na+/K+ pump transports Na+ and K+ ions in opposite directions across the plasma membrane.
For each cycle of the pump, three Na+ ions are transported out of the cell, and two K+ ions are transported into the cell.
Transport is active in each case because both types of ions move up their electrochemical gradients.
The Na+/K+ pump is responsible for creating the concentration gradients of Na+ and K+ listed in Table 4.1.
Secondary Active Transport
In secondary active transport, a transport protein couples the flow of one substance to that of another.
One substance moves passively down its electrochemical gradient, releasing energy that is then used to drive the movement of the other substance up its electrochemical gradient.
Secondary active transport may involve either cotransport or countertransport.
Factors Affecting Rates of Active Transport
The rate of active transport is determined by the rate of transport by individual active transporters and the number of active transporters present in the membrane.
Coexistence of Active and Passive Transport Mechanisms in Cells
Intracellular and extracellular fluids differ substantially in composition.
These differences are created when certain substances are actively transported into or out of cells, increasing or decreasing the concentrations of these substances in intracellular fluid with respect to extracellular fluid.
Normally, the composition of intracellular fluid remains fairly steady.
If substances are actively transported into or out of cells, why don’t intracellular concentrations change?
The answer lies in the fact that these substances are simultaneously transported passively (leaked) across the membrane in the opposite direction but at the same rate, such that the net flux across the membrane (active and passive transport combined) is zero (Figure 4.16).
Even though Na+ ions, for example, are actively transported out of cells by the Na+/K+ pump, they leak passively into cells through channels and other proteins.
For every Na+ ion that is transported out under normal conditions, another leaks in passively, such that the intracellular Na+ concentration does not change.
Likewise, for every K+ ion that is actively transported in, another passively leaks out, such that the intracellular K+ concentration does not change.
Osmosis: Passive Transport of Water Across Membranes
Normally, the amount of water contained in cells remains fairly steady, but it can change significantly in certain extreme or pathological conditions.
In some types of kidney dysfunction, for instance, excess water is retained in the body and begins to move into cells, causing them to swell.
The swelling of brain cells disrupts nervous system function and typically produces headache, nausea, and vomiting, indicating that a condition known as water intoxication has occurred.
Severe cases can progress to seizures, coma, and death.
In contrast, severe dehydration can cause water to move out of cells, such that the cells then shrink. This effect is also detrimental to brain function and can even be fatal.
Under normal conditions, most cells in the body neither swell nor shrink because there is no net movement of water across membranes; forces that might cause water to cross membranes are absent.
In some locations in the body, however, movement of water across cell membranes is a normal occurrence.
For glands to secrete fluids such as sweat, tears, or saliva, for instance, water must be transported across specialized epithelial cells.
Also, when you drink water, it moves across the epithelial cells lining the intestine to be absorbed into the bloodstream.
Such water movement is important because it ultimately affects the volume and composition of all body fluids.
Water transport has always had a “special” status in physiology because of its influence on cell volume, and because its description has its own unique terminology.
Water transport is simple because water flow across membranes is always passive, is unaffected by membrane potentials, and is always driven by its own concentration gradient.
The flow of water across a membrane down its concentration gradient is called osmosis.
The effects of osmosis are familiar to nearly everyone who has studied high school biology.
When you place red blood cells in pure water, water flows into the cells, which then swell up, burst, and release hemoglobin into the water, a process called hemolysis.
Figure 4.17 depicts the conditions that drive osmosis.
When a red blood cell is placed in pure water, water molecules flow into the cell because in doing so they are flowing down their concentration gradient.
This gradient results from the presence within the cell of various solutes (Na+, K+, and proteins, among others) at a combined concentration of about 300 millimolar.
The presence of these solute molecules reduces the water concentration inside the cell by taking up a certain amount of space that would have been occupied by water molecules, which means that fewer water molecules are present in a given volume of solution.
In other words, the concentration of water within the cell is lower than outside the cell.
At body temperature, the concentration of pure water is 55.5 molar, and the normal total solute concentration in intracellular fluid is 300 millimolar (0.3 molar).
Thus the intracellular water concentration is roughly 55.2 molar (55.5 molar - 0.3 molar; see Figure 4.17a).
Therefore, when a cell is placed in pure water, there is a 0.3 molar smaller water concentration inside it than outside it; as a consequence, water molecules move passively into the cell down their concentration gradient, causing the cell to swell and eventually burst.
The direction of passive water flow into or out of a cell depends on the direction of the water concentration gradient across the plasma membrane.
For instance, when a cell is placed in a solution of sucrose at a concentration of 1 molar (1000 millimolar), the cell shrinks because water moves out (Figure 4.17b).
Outward water movement occurs because the total solute concentration is lower inside the cell than it is outside, which makes the water concentration higher inside the cell.
Therefore, water moves passively out of the cell.
Concentrations of solutions are usually described in terms of the concentration of solute, not solvent.
Concentrations of solute and solvent vary inversely.
Thus, in osmosis, water movement occurs from a low concentration of solute to a high concentration of solute.
The term solute particle is often used to reflect that some solutes separate into more than one particle when placed in a solution; each of these resultant particles will have an osmotic influence on movement of the solvent.
Osmolarity
The total solute particle concentration of a solution is known as its osmolarity.
A solution containing 1 mole of solute particles is said to be at a concentration of 1 osmolar (1 Osm).
One mole of solute particles is referred to as 1 osmole.
We use the term solute particle to distinguish osmolar from molar because certain solutes when put into solution dissociate into particles, and each solute particle present decreases the concentration of water.
For example, 1 liter of a solution containing 0.1 mole of glucose has an osmolarity of 0.1 osmolar because glucose does not dissociate in solution.
However, a 1-liter solution containing 0.1 mole of NaCl has an osmolarity of approximately 0.2 osmolar because NaCl dissociates in solution to give approximately 0.1 mole of sodium ions and 0.1 mole of chloride ions, for a total of 0.2 mole of solute particles.
Osmolarity also depends on the total concentration of all solute particles.
Thus a 1-liter solution containing 0.1 mole of glucose plus 0.1 molar NaCl is a 0.3 osmolar solution.
In physiology, the terms milliosmole and milliosmolar (mOsm) are frequently used because the solute concentration of body fluids is only a fraction of 1 osmolar.
A 1 milliosmolar (1 mOsm) solution contains 1 milliosmole (1/1000 of an osmole) of solute particles per liter.
The normal osmolarity of intracellular and extracellular fluid is approximately 300 mOsm (the actual range is 280–296 mOsm), which means that its total solute concentration is 300 milliosmoles per liter.
Two solutions having the same osmolarity are said to be iso-osmotic.
Thus a 300 millimolar glucose solution is iso-osmotic with intracellular fluid because both solutions are 300 milliosmolar.
A solution whose osmolarity is higher than another is said to be hyperosmotic; a solution with lower osmolarity is hypo-osmotic.
When two solutions are iso-osmotic, they have not only the same solute concentration but also the same water concentration.
In a hyperosmotic solution, the water concentration is lower because the solute concentration is higher.
In a hypo-osmotic solution, the water concentration is higher because the solute concentration is lower.
Osmotic Pressure
Osmotic pressure is another term that describes a solution’s total solute concentration; it is often used when comparing other physiological forces described in terms of pressure.
The osmotic pressure of a solution (which is indicated by the symbol π) is an indirect measure of its solute concentration and is expressed in ordinary units of pressure, such as atmospheres or millimeters of mercury (mm Hg).
As the total solute concentration (osmolarity) increases, the osmotic pressure increases.
Therefore, when water moves by osmosis from low solute concentration to high solute concentration, water is also flowing up an osmotic pressure gradient (Figure 4.18).
In Figure 4.18, the total solute concentration on the left side of the semipermeable membrane (side 1) is less than that on the right (side 2), making the osmotic pressure on side 2 higher.
Thus, as water moves from side 1 (low solute concentration) to side 2 (high solute concentration), water is flowing from lower to higher osmotic pressure, or up the osmotic pressure gradient (Δπ).
Note that the tendency of water to flow up an osmotic pressure gradient does not violate the rules concerning gradients, which state that substances tend to move passively down chemical and electrochemical gradients.
When water moves up a gradient of osmotic pressure, it is merely moving down a chemical gradient—its own concentration gradient.
Tonicity
When someone suffers massive hemorrhage, it is quite common for emergency medical personnel to administer a saline (sodium chloride) solution intravenously to replace the lost blood volume.
This procedure is done to keep the person alive while awaiting a blood transfusion.
The administered solution is referred to as isotonic saline because its total solute concentration has been carefully formulated to match that of extracellular fluid.
Such a solution will not alter cell volumes when injected into the bloodstream.
In contrast, a more concentrated saline solution would cause water to flow out of cells, making them shrink; a less concentrated solution would cause water to flow into cells, making them swell.
Whereas a solution’s osmolarity is based solely on its total solute concentration, its tonicity is a function of the concentration of nonpermeating solutes outside a cell relative to the concentration inside the cell, and it determines the behavior of a cell placed in the solution.
A solution is said to be isotonic when it does not alter cell volume; when a cell comes into contact with an isotonic solution, it neither shrinks nor swells.
In contrast, a solution that causes cells to shrink is hypertonic, whereas a solution that causes cells to swell is hypotonic.
The distinction between osmolarity and tonicity is best illustrated in the situation depicted in Figure 4.19.
Initially, the cell is placed in a 300 mOsm solution of urea, a substance that permeates most cell membranes readily (Figure 4.19a).
The osmolarity of this solution equals the initial osmolarity inside the cell (300 mOsm), making it iso-osmotic with the intracellular fluid.
Under these conditions, water does not move into or out of the cell because the water concentration is the same on both sides of the cell membrane.
Over time, urea moves into the cell due to the initial presence of an inwardly directed concentration gradient (Figure 4.19b).
Intracellular solutes, in contrast, are retained inside the cell because they are relatively impermeant; that is, they cannot permeate the membrane.
As a result of urea movement, the cell gains solute, and the osmolarity of the intracellular fluid increases so that it exceeds its initial value of 300 mOsm.
Because the total solute concentration is now higher inside the cell than outside, water moves into the cell, and the cell swells.
The cell swells even though the extracellular solution is originally iso-osmotic to the intracellular fluid.
Because the cell swells, the extracellular solution is hypotonic.
Whether a given solution causes cells to swell, shrink, or stay the same is determined solely by the concentration of impermeant solutes contained in it.
A solution is isotonic if it contains impermeant solutes at a concentration of 300 mOsm, the normal concentration of impermeant solutes in intracellular fluid.
If the concentration of impermeant solutes is either greater or less than 300 mOsm, the solution will be hypertonic or hypotonic, respectively.
A solution’s tonicity is not affected by the concentration of any permeant solutes that may or may not be present.
The characteristics that determine a solution’s osmolarity or tonicity are summarized in Table 4.3.
When a cell comes into contact with solutions that are hypotonic or hypertonic, the degree to which it swells or shrinks is determined by the initial concentrations of impermeant solutes in intracellular and extracellular fluid.
For example, when a cell containing 300 mOsm impermeant solutes is placed in a large volume of solution containing impermeant solutes at half that concentration (150 mOsm), the cell will swell because water flows in (Figure 4.20a).
Because the amount of solute inside the cell is fixed, the increase in cell volume causes the intracellular solute concentration to decrease, but the cell continues to swell until the concentration reaches 150 mM, at which point the cell has expanded to twice its original volume (designated Vo).
Swelling stops at this point because there is no longer a concentration gradient of water, and hence no driving force to cause water to flow across the membrane.
By contrast, when an identical cell is placed in a solution containing 600 mOsm impermeant solutes (Figure 4.20b), it shrinks, which causes the intracellular solute concentration to rise.
The cell continues to shrink until the concentration inside the cell reaches 600 mOsm, at which point it has shrunk to half of its original volume.
Transport of Material Within Membrane-Bound Compartments
Macromolecules are too large to cross the plasma membrane even with the assistance of proteins; thus they are transported across with the assistance of vesicles.
During endocytosis, molecules in the extracellular fluid enter the cell through the formation of vesicles, called endosomes, from the plasma membrane.
During exocytosis, molecules within cells are packaged into secretory vesicles, which then fuse with the plasma membrane and release their contents into the extracellular fluid.
Both of these processes, which require the input of energy, are described next.
Transport of Molecules into Cells by Endocytosis
There are three forms of endocytosis: phagocytosis, pinocytosis, and receptor-mediated endocytosis (Figure 4.21).
In all cases, extracellular fluid and sometimes particulate matter are brought into the cell by the formation of an endosome.
In phagocytosis (which means “cell-eating”), a cell uses amoeboid-like movements of its plasma membrane to extend the membrane around particulate matter in the extracellular fluid (see Figure 4.21a).
When the membrane completely surrounds the particle, the two sides of the plasma membrane pinch together to form a large endosome called a phagosome in the cytoplasm; the particle and some extracellular fluid are inside the vesicle.
In this manner, the cell engulfs the particle.
Once inside the cell, the membrane of the phagosome fuses with the membrane of a lysosome, forming a phagolysosome, which exposes the engulfed particle to the degradative enzymes of the lysosome.
The enzymes break down the particle and usable components are recycled.
Phagocytosis is common in certain white blood cells, which are responsible for removing foreign particles and bacteria from our bodies.
In pinocytosis (which means “cell-drinking”), the plasma membrane develops an indentation, and its outer edges pinch together to form an endosome in the cytoplasm (see Figure 4.21b).
Pinocytosis, which occurs continuously in most cells, is a nonspecific process, and the contents of the resulting vesicle comprise extracellular fluid containing dissolved solutes.
Receptor-mediated endocytosis is similar to pinocytosis in that the plasma membrane develops an indentation to form the endosome (see Figure 4.21c).
Unlike pinocytosis, however, receptor-mediated endocytosis is specific.
Proteins in the plasma membrane function as receptors that recognize and bind specific particles in the extracellular fluid.
Binding of particles to receptors concentrates the particles to areas where endocytosis will occur.
The area of plasma membrane that forms the vesicle is coated with proteins, called clathrin, on its cytosolic surface.
The membrane indents in this area, forming what is called a coated pit.
The coated pit becomes a coated vesicle containing the receptors and the particles bound to them.
The protein coat rapidly leaves the vesicle, and the clathrin molecules are recycled.
The now uncoated vesicle fuses with a lysosome, forming an endolysosome.
The enzymes in the lysosome will degrade the particles brought into the cell.
The receptors are often recycled by exocytosis, which is described next.
Transport of Molecules Out of Cells by Exocytosis
Exocytosis is basically endocytosis in reverse: A vesicle inside the cell fuses with the plasma membrane and releases its contents into the extracellular fluid (Figure 4.22).
Exocytosis involves complex interactions between calcium and proteins, the process of which will be described for neurons (in Chapter 8).
Exocytosis has three functions: (1) to add components to the plasma membrane, (2) to recycle receptors removed from the plasma membrane by endocytosis, and (3) to secrete specific substances out of the cell and into the extracellular fluid.
The first two functions are related in that both add components to the plasma membrane.
During exocytosis, whatever components are present in the vesicle membrane will be added to the plasma membrane.
A cell can add certain proteins, phospholipids, or carbohydrates to the plasma membrane, or it can replace the membrane that is lost during endocytosis.
In fact, endocytosis and exocytosis must be balanced in a cell; otherwise, the size of the plasma membrane will change.
The third function of exocytosis, the secretion of materials, serves a number of functions.
Certain white blood cells secrete antibodies to fight infections.
Most cells—in particular, neurons and endocrine cells—secrete chemical messengers that communicate with other cells.
Cells lining certain hollow ducts or passageways, such as the gastrointestinal tract or respiratory airways, secrete a sticky fluid called mucus, which acts as a protective coating.
Epithelial Transport: Movement of Molecules Across Two Membranes
Up to this point, we have been focusing on cell membrane function as it pertains to the transport of materials into or out of cells.
In many epithelial tissues, cell membranes function to transport materials across cells.
This occurs, for instance, when the intestine delivers nutrients to the bloodstream, or when sweat glands produce sweat.
Epithelial tissues form barriers between the body’s internal environment and the external environment, as well as between different fluid compartments within the body.
Certain epithelia (such as those lining the stomach, intestine, and secretory glands) are able to transport materials into the internal environment from outside (absorption) or from the internal environment to the outside (secretion).
For an epithelium to absorb or secrete materials, the cells must transport substances inward across the membrane on one side of the cell and outward across the membrane on the opposite side.
The membranes on either side must possess different transport systems.
Epithelial cells are said to be polarized because the membranes on the two sides are distinctly different in both structure and function.
Epithelial Structure
In an epithelial cell layer specialized for absorption or secretion, one side of an epithelial cell faces the lumen of a body cavity. This membrane is called the apical membrane.
The membrane on the opposite side faces the internal environment and is in contact with interstitial fluid, which exchanges materials with the blood. This blood-facing membrane is called the basolateral membrane.
The basolateral membrane rests on a basement membrane consisting of noncellular material that is relatively permeable to most substances.
The basement membrane anchors the basolateral membrane and provides physical support for the epithelial layer.
Adjacent cells are joined by tight junctions that limit the passage of material through the spaces between cells called paracellular spaces.
These junctions permit the fluids on either side of the cell layer to differ in composition.
Tight junctions are important in maintaining homeostasis because they ensure that the composition of interstitial fluid remains consistent, even if the composition of fluid in the lumen of an organ varies widely.
The “tightness” of these junctions varies from location to location; tight epithelia have junctions with extremely low permeabilities, whereas leaky epithelia have junctions that are more permeable.
Epithelial Solute Transport
The mechanisms whereby epithelial cells transport solute molecules across an epithelial layer are illustrated in Figure 4.24.
A comparison of the transport systems in the apical and basolateral membranes of epithelial cells reveals their polarity.
Only the basolateral membranes have Na+/K+ pumps, which transport Na+ out of the cell and K+ into the cell.
Only the basolateral membranes possess K+ channels, which allow K+ to leak out of the cells down its electrochemical gradient.
This pump-leak system maintains a nearly constant concentration of K+ inside the cells that is higher than the concentration outside the cells.
The Na+/K+ pump also maintains a low Na+ concentration inside the cells, creating an inwardly directed Na+ gradient.
The apical membrane possesses transport systems that the basolateral membrane lacks.
Epithelial Water Transport
Whenever epithelial cells secrete or absorb fluid, water transport occurs by osmosis.
Epithelia absorb or secrete water by first using the active transport of solutes to create a difference in osmotic pressure—an osmotic pressure gradient—between the solutions on either side of the cell layer.
Water then flows across the epithelium passively by osmosis.
Water transport is secondary to solute transport because it occurs in response to the transport of solutes.
In epithelial water transport, an epithelium creates an osmotic pressure gradient to absorb water.
Epithelial cells actively transport solute molecules across the basolateral membrane into the interstitial fluid.
The solute concentration is slightly higher outside the cells than inside, particularly in the paracellular spaces.
This solute transport creates a difference in osmotic pressure between the solutions on either side of the epithelium, causing water to flow across the cell layer by osmosis.
The direction of water flow is toward interstitial fluid, or up the osmotic pressure gradient.
For epithelia that secrete fluids, solute and water transport go in the opposite direction—away from interstitial fluid.
Transcytosis
Macromolecules cross epithelial cells by a process called transcytosis, which involves both endocytosis and exocytosis.
During transcytosis, a large molecule is taken into the cell by endocytosis, but the endocytotic vesicle does not fuse with a lysosome.
Instead, the vesicle travels to the opposite side of the cell and fuses with the plasma membrane to release its content by exocytosis.