CHAPTER 4 Transport of Substances through the Cell Membranes

Differences between the composition of intracellular and extracellular fluids are caused by transport mechanisms of cell membranes. These differences include the following:

• Extracellular fluid has a high sodium concentration, high chloride concentration, and low potassium concentration. The opposite is true of intracellular fluid.

• The concentrations of phosphates and proteins in intracellular fluid are greater than those in extracellular fluid.

The Cell Membrane Consists of a Lipid Bilayer with “Floating” Protein Molecules

The lipid bilayer constitutes a barrier for the movement of most water-soluble substances. However, most lipid-soluble substances can pass directly through the lipid bilayer. Protein molecules in the lipid bilayer constitute an alternate transport pathway.

• Channel proteins provide a watery pathway for molecules to move through the membrane.

• Carrier proteins bind with specific molecules and then undergo conformational changes that move molecules through the membrane.

Transport through the Cell Membrane Occurs through Diffusion or Active Transport

• Diffusion means random movement of molecules either through intermolecular spaces in the cell membrane or in combination with a carrier protein. The energy that causes diffusion is the energy of the normal kinetic motion of matter.

• Active transport means movement of substances across the membrane in combination with a carrier protein but also against an electrochemical gradient. This process requires a source of energy in addition to kinetic energy.

Diffusion (p. 46)

Diffusion Is the Continual Movement of Molecules in Liquids or Gases

Diffusion through the cell membrane is divided into the following two subtypes:

• Simple diffusion means that molecules move through a membrane without binding with carrier proteins. Simple diffusion can occur by way of two pathways: (1) through the interstices of the lipid bilayer and (2) through watery channels in transport proteins that span the cell membrane.

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• Facilitated diffusion requires a carrier protein. The carrier protein aids in passage of molecules through the membrane, probably by binding chemically with them and shuttling them through the membrane in this form.

The Rate of Diffusion of a Substance through the Cell Membrane Is Directly Proportional to Its Lipid Solubility

The lipid solubilities of oxygen, nitrogen, carbon dioxide, anesthetic gases, and most alcohols are so high they can dissolve directly in the lipid bilayer and diffuse through the cell membrane.

Water and Other Lipid-Insoluble Molecules Diffuse through Protein Channels in the Cell Membrane

Water readily penetrates the cell membrane and can also pass through transmembrane protein channels. Other lipid-insoluble molecules (mainly ions) can pass through the water-filled protein channels in the same way as water molecules if they are sufficiently small.

Protein Channels Have Selective Permeability for Transport of One or More Specific Molecules

This permeability results from the characteristics of the channel itself, such as its diameter, its shape, and the nature of the electrical charges along its inside surfaces.

Gating of Protein Channels Provides a Means for Controlling Their Permeability

The gates are thought to be gatelike extensions of the transport protein molecule, which can close over the channel opening or be lifted from the opening by a conformational change in the protein molecule itself. The opening and closing of gates are controlled in two principal ways:

• Voltage gating. In this instance, the molecular conformation of the gate responds to the electrical potential across the cell membrane. For example, the normal negative charge on the inside of the cell membrane causes the sodium gates to remain tightly closed. When the inside of the membrane loses its negative charge (becomes less negative), these gates open allowing sodium ions to pass inward through the sodium channels. The opening of sodium channel gates is the basic cause of action potentials in nerves.

• Chemical gating. Some protein channel gates are opened by the binding of another molecule with the protein; this causes a conformational change in the protein molecule that opens or closes the gate. This is called chemical (or ligand) gating. One of the most important instances of chemical gating is the effect of acetylcholine on the “acetylcholine channel” of the neuromuscular junction.

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Facilitated Diffusion Is Also Called Carrier-Mediated Diffusion

A substance transported in this manner usually cannot pass through the cell membrane without the assistance of a specific carrier protein.

• Facilitated diffusion involves the following two steps: (1) the molecule to be transported enters a blind-ended channel and binds to a specific receptor and (2) a conformational change occurs in the carrier protein, so the channel now opens to the opposite side of the membrane.

• Facilitated diffusion differs from simple diffusion in the following important way. The rate of simple diffusion increases proportionately with the concentration of the diffusing substance. With facilitated diffusion, the rate of diffusion approaches a maximum as the concentration of the substance increases. This maximum rate is dictated by the rate at which the carrier protein molecule can undergo the conformational change.

• Among the most important substances that cross cell membranes through facilitated diffusion are glucose and most of the amino acids.

Factors That Affect the Net Rate of Diffusion (p. 50)

Substances Can Diffuse in Both Directions through the Cell Membrane

Therefore, what is usually important is the net rate of diffusion of a substance in the desired direction. This net rate is determined by the following factors:

• Permeability. The permeability of a membrane for a given substance is expressed as the net rate of diffusion of the substance through each unit area of the membrane for a unit concentration difference between the two sides of the membrane (when there are no electrical or pressure differences).

• Concentration difference. The rate of net diffusion through a cell membrane is proportional to the difference in concentration of the diffusing substance on the two sides of the membrane.

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• Electrical potential. If an electrical potential is applied across a membrane, the ions move through the membrane because of their electrical charges. When large amounts of ions have moved through the membrane, a concentration difference of the same ions develops in the direction opposite to the electrical potential difference. When the concentration difference rises to a sufficiently high level, the two effects balance each other creating a state of electrochemical equilibrium. The electrical difference that balances a given concentration difference can be determined with the Nernst equation.

Osmosis across Selectively Permeable Membranes—“Net Diffusion of Water” (p. 51)

Osmosis Is the Process of Net Movement of Water Caused by a Concentration Difference of Water

Water is the most abundant substance to diffuse through the cell membrane. However, the amount that diffuses in each direction is so precisely balanced under normal conditions that not even the slightest net movement of water occurs. Therefore, the volume of a cell remains constant. However, a concentration difference for water can develop across a cell membrane. When this happens, net movement of water occurs across the cell membrane, causing the cell to either swell or shrink, depending on the direction of the net movement. The pressure difference required to stop osmosis is the osmotic pressure.

The Osmotic Pressure Exerted by Particles in a Solution Is Determined by the Number of Particles per Unit Volume of Fluid and Not by the Mass of the Particles

On average, the kinetic energy of each molecule or ion that strikes a membrane is about the same regardless of its molecular size. Consequently, the factor that determines the osmotic pressure of a solution is the concentration of the solution in terms of number of particles per unit volume but not in terms of mass of the solute.

The Osmole Expresses Concentration in Terms of Number of Particles

One osmole is 1 g molecular weight of undissociated solute. Thus 180 g of glucose, which is 1 g molecular weight of glucose, is equal to 1 osmole of glucose because glucose does not dissociate. A solution that has 1 osmole of solute dissolved in each kilogram of water is said to have an osmolality of 1 osmole per kilogram, and a solution that has 1/1000 osmole dissolved per kilogram has an osmolality of 1 milliosmole per kilogram. The normal osmolality of the extracellular and intracellular fluids is about 300 milliosmoles per kilogram, and the osmotic pressure of these fluids is about 5500 mm Hg.

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“Active Transport” of Substances through Membranes (p. 52)

Active Transport Can Move a Substance against an Electrochemical Gradient

An electrochemical gradient is the sum of all the diffusion forces acting at the membrane—the forces caused by a concentration difference, an electrical difference, and a pressure difference. That is, substances cannot diffuse “uphill.” When a cell membrane moves a substance uphill against a concentration gradient (or uphill against an electrical or pressure gradient), the process is called active transport.

Active Transport Is Divided into Two Types According to the Source of the Energy Used to Effect the Transport

In both instances, transport depends on carrier proteins that penetrate the membrane, which is also true for facilitated diffusion.

• Primary active transport. The energy is derived directly from the breakdown of adenosine triphosphate (ATP) or some other high-energy phosphate compound.

• Secondary active transport. The energy is derived secondarily from energy that has been stored in the form of ionic concentration differences between the two sides of a membrane, originally created by primary active transport. The sodium electrochemical gradient drives most secondary active transport processes.

Primary Active Transport (p. 53)

The Sodium-Potassium (Na⁺-K⁺) Pump Transports Sodium Ions out of Cells and Potassium Ions into Cells

This pump is present in all cells of the body, and it is responsible for maintaining the sodium and potassium concentration differences across the cell membrane as well as for establishing a negative electrical potential inside the cells. The pump operates in the following manner. Three sodium ions bind to a carrier protein on the inside of the cell, and two potassium ions bind to the carrier protein on the outside of the cell. The carrier protein has ATPase activity, and the simultaneous binding of sodium and potassium ions causes the ATPase function of the protein to become activated. This then cleaves one molecule of ATP, splitting it to form adenosine diphosphate (ADP) and liberating a high-energy phosphate bond of energy. This energy is then believed to cause a conformational change in the protein carrier molecule, extruding the sodium ions to the outside and the potassium ions to the inside.

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The Na⁺-K⁺ Pump Controls Cell Volume

The Na⁺-K⁺ pump transports three molecules of sodium to the outside of the cell for every two molecules of potassium pumped to the inside. This continual net loss of ions from the cell interior initiates an osmotic force to move water out of the cell. Furthermore, when the cell begins to swell, this automatically activates the Na⁺-K⁺ pump, moving to the exterior still more ions that are carrying water with them. Therefore, the Na⁺-K⁺ pump performs a continual surveillance role in maintaining normal cell volume.

Active Transport Saturates in the Same Way That Facilitated Diffusion Saturates

When the difference in concentration of the substance to be transported is small, the rate of transport rises approximately in proportion to increases in its concentration. At high concentrations, the rate of transport is limited by the rates at which the chemical reactions of binding, release, and carrier conformational changes can occur.

Co-Transport and Counter-Transport Are Two Forms of Secondary Active Transport

When sodium ions are transported out of cells by primary active transport, a large concentration gradient of sodium normally develops. This gradient represents a storehouse of energy because the excess sodium outside the cell membrane is always attempting to diffuse to the cell interior.

• Co-transport. The diffusion energy of sodium can pull other substances along with the sodium (in the same direction) through the cell membrane using a special carrier protein.

• Counter-transport. The sodium ion and substance to be counter-transported move to opposite sides of the membrane, with sodium always moving to the cell interior. Here again, a protein carrier is required.

Glucose and Amino Acids Can Be Transported into Most Cells through Sodium Co-Transport

The transport carrier protein has two binding sites on its exterior side—one for sodium and one for glucose or amino acids. Again, the concentration of sodium ions is very high on the outside and very low on the inside, providing the energy for the transport. A special property of the transport protein is that the conformational change to allow sodium movement to the cell interior does not occur until a glucose or amino acid molecule also attaches.

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Calcium and Hydrogen Ions Can Be Transported out of Cells through the Sodium Counter-Transport Mechanism

• Calcium counter-transport occurs in most cell membranes, with sodium ions moving to the cell interior and calcium ions moving to the exterior, both bound to the same transport protein in a counter-transport mode.

• Hydrogen counter-transport occurs especially in the proximal tubules of the kidneys, where sodium ions move from the lumen of the tubule to the interior of the tubular cells, and hydrogen ions are counter-transported into the lumen.