Porth's Essentials of Pathophysiology, 4e

14

Cell and Tissue Function

U N I T 1

S

Na +

S Na +

Extracellular

Extracellular

Intracellular

Intracellular

S Na +

S Na +

A Symporter

B Antiporter

FIGURE 1-11. Secondary active transport systems. (A) Symport or cotransport carries the transported solute (S) in the same direction as the sodium (Na + ) ion. (B) Antiport or countertransport carries the solute and Na + in the opposite direction.

A host of genetic disorders known as channelopathies involve mutations in channel proteins. For example, in cystic fibrosis (see Chapter 23), the primary defect resides in an abnormal chloride channel, which results in increased sodium and water reabsorption that causes respiratory tract secretions to thicken and occlude the airways. Diffusion Diffusion refers to the passive process by which mol- ecules and other particles in a solution become widely dispersed and reach a uniform concentration because of energy created by their spontaneous kinetic movements. In the process of reaching a uniform concentration, these molecules and particles move “downhill” from an area of higher to an area of lower concentration. If the molecules or particles carry a net charge, both the concentration gradient and the electrical potential dif- ference across the membrane influence transport. Lipid-soluble molecules, such as oxygen, carbon dioxide, alcohol, and fatty acids, become dissolved in the lipid matrix of the cell membrane and diffuse through the membrane in the same manner that diffu- sion occurs in water. Other substances diffuse through minute pores of the cell membrane. Simple Diffusion. Simple diffusion means that the kinetic movement of molecules or ions occurs through a membrane opening or through intermolecular spaces without any interaction with a carrier protein. The rate of diffusion depends on how many particles are avail- able for diffusion, the kinetic movement of the particles, and the number and size of the openings in the mem- brane through which the molecules or ions can move. Facilitated Diffusion. Like simple diffusion, facilitated diffusion occurs down a concentration gradient; thus, it does not require input of metabolic energy. Unlike simple diffusion, however, facilitated diffusion requires a trans- port protein. Some substances, such as glucose, can- not pass unassisted through the cell membrane because they are not lipid soluble or they are too large to pass through the membrane’s pores. These substances com- bine with special transport proteins at the membrane’s

outer surface, are carried across the membrane attached to the transporter, and then are released. In facilitated diffusion, a substance can move only from an area of higher concentration to one of lower concentration. The rate at which a substance moves across the membrane by facilitated diffusion depends on the difference in con- centration between the two sides of the membrane. Also important are the availability of transport proteins and the rapidity with which they can bind and release the substance being transported. It is thought that insulin, which facilitates the movement of glucose into cells, acts by increasing the availability of glucose transporters in the cell membrane. Ion Channels and Gates. Ion channels (leak channels) are integral proteins that span the width of the membrane and are normally composed of several polypeptides or protein subunits that form a gating system (Fig. 1-12). Specific stimuli cause the protein subunits to undergo conformational changes to form an open channel or gate through which the ions can move. In this way, ions do not need to cross the lipid-soluble portion of the membrane but can remain in the aqueous solution that fills the ion channel. Many of the ion channels are highly selective for transport of one or more specific ions or molecules. This selectivity results from the characteristics of the channel itself, such as its diameter, its shape, and the nature of elec- trical charges and chemical bonds along its inside surface. The cell membrane contains two basic groups of ion channels: leakage channels and gated channels. Leakage channels are open even in the unstimulated state, whereas gated channels open and close in response to specific stimuli. Three main types of gated channels are present in the cell membrane: voltage-gated chan- nels , which have electrically operated channels that open when the membrane potential changes beyond a certain point; ligand-gated channels , which are chemi- cally operated and respond to specific receptor-bound ligands, such as the neurotransmitter acetylcholine; and mechanically gated channels , which open or close in response to such mechanical stimulations as vibrations, tissue stretching, or pressure. Movement of Water Across the Cell Membrane. Water molecules move through adjacent phospholipid