Y. Uehara, J. Neurocytol. 10:101–110, 1981. With permission from Kluwer Academic Publishers.) extracellular concentration of Ca2+ is so much lower than that of Na+ that Ca2+ makes only a small contribution to the total inward current.) Therefore, the opening of the acetylcholine-receptor channels leads to a large net influx of Na+ (a peak rate of about 30,000 ions per channel each millisecond). This influx causes a membrane depolarization that signals the muscle to contract, as discussed below.
Neurons Contain Many Types of Transmitter-Gated Channels
The ion channels that open directly in response to the neurotransmitters acetylcholine, serotonin, GABA, and glycine contain subunits that are structurally similar and probably form transmembrane pores in the same way as the ionotropic acetylcholine receptor, even though they have distinct neurotransmitter-binding specificities and ion selectivities. These channels are all built from homologous polypeptide subunits, which assemble as a pentamer. Glutamate-gated ion channels are an exception, in that they are constructed from a distinct family of subunits and form tetramers resembling the K+ channels discussed earlier (see Figure 11–24A).
For each class of transmitter-gated ion channel, there are alternative forms of each type of subunit, which may be encoded by distinct genes or else generated by alternative RNA splicing of a single gene product. The subunits assemble in different combinations to form an extremely diverse set of distinct channel subtypes, with different ligand affinities, different channel conductances, different rates of opening and closing, and different sensitivities to drugs and toxins. Some vertebrate neurons, for example, have acetylcholine-gated ion channels that differ from those of muscle cells in that they are formed from two subunits of one type and three of another; but there are at least nine genes coding for different versions of the first type of subunit and at least three coding for different versions of the second. Subsets of such neurons performing different functions in the brain express different combinations of the genes for these subunits. In principle, and already to some extent in practice, it is possible to design drugs targeted against these narrowly defined subsets, thereby specifically influencing particular brain functions.
Transmitter-gated ion channels have for a long time been important drug targets. A surgeon, for example, can relax muscles for the duration of an operation