helices (Fig. 11-51b), which draws these hydrophobic side chains away from the center of the channel, opening it to the passage of ions.

Based on similarities between the amino acid sequences of other ligand-gated ion channels and the acetylcholine receptor, the receptor channels that respond to the extracellular signals y-aminobutyric acid (GABA), glycine, and serotonin have been classified in the acetylcholine receptor superfamily, and probably share three-dimensional structure and gating mechanisms. The GABAa and glycine receptors are anion channels specific for Cl" or HCOjT, whereas the serotonin receptor, like the acetylcholine receptor, is cation-specific. The subunits of each of these channels, like those of the acetylcholine receptor, have four transmembrane helical segments and form oligomeric channels.

A second class of ligand-gated ion channels respond to intracellular ligands: 3',5'-cyclic guanosine mononucleotide (cGMP) in the vertebrate eye, cGMP and cAMP in olfactory neurons, and ATP and inositol 1,4,5-trisphosphate (IP3) in many cell types. These channels are composed of multiple subunits, each with six transmembrane helical domains. We discuss the signaling functions of these ion channels in Chapter 12.

Table 11-7 shows a number of transporters not discussed in this chapter but encountered later in the book in the context of the paths in which they act.

Defective Ion Channels Can Have Adverse Physiological Consequences

The importance of ion channels to physiological processes is clear from the effects of mutations in specific ion-channel proteins (Table 11-8). Genetic defects in the voltage-gated Na+ channel of the myocyte plasma membrane result in diseases in which muscles are periodically either paralyzed (as in hyperkalemic pe riodic paralysis) or stiff (as in paramyotonia congenita). As noted earlier, cystic fibrosis is the result of a mutation that changes one amino acid in the protein CFTR, a Cl" ion channel; the defective process here is not neurotransmission but secretion by various exocrine gland cells whose activities are tied to Cl" ion fluxes.

Many naturally occurring toxins act on ion channels, and the potency of these toxins further illustrates the importance of normal ion-channel function. Tetro-dotoxin (produced by the puffer fish, Sphaeroides rubripes) and saxitoxin (produced by the marine di-noflagellate Gonyaulax, which causes "red tides") act by binding to the voltage-gated Na+ channels of neurons and preventing normal action potentials. Puffer fish is an ingredient of the Japanese delicacy fugu, which may be prepared only by chefs specially trained to separate



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