The Family of Neurotransmittergated Ion Channels

In Chapter 8, we learned that the ACh-gated channel is formed by the aggregation of several protein subunits. The other kinds of ion channels that underlie excitatory and inhibitory postsynaptic potentials have also been studied at the molecular level, and like the ACh-gated channel, these ion channels are formed by aggregates of individual subunits. Each type of subunit is encoded by a specific gene. The amino-acid sequences of subunits making up the neurotransmitter-gated channels are more or less similar. For example, GABA-activated channels are structurally similar to glycine-activated channels and ACh-activated channels. Glutamate-activated channels also are related to ACh-activated channels, although more distantly. Therefore, the genes encoding the subunits of the neurotransmitter-gated ion channels constitute a family of related genes, called the ligand-gated ion channel family. As the name implies, members of the family form ion channels that are opened by the binding of a chemical signal (the ligand) to a specific binding site on the channel.

Of course, there are also important functional differences among the members of this gene family. First, each channel type must be specifically activated by a particular neurotransmitter: a glutamate-activated channel is not activated by GABA, even though glutamate and GABA are structurally quite similar (Figures 9-5, 9-10). (In fact, GABA is formed enzymatically by modification of glutamate.) Thus, the part of the protein that forms the neuro-transmitter binding site must be unique for each type of ligand-gated channel. Second, the ion-conducting pore differs among members of the ligand-gated ion channel family. Some ligand-gated channels form cation pores (e.g., glutamate-gated channels or ACh-gated channels), whereas others form anion pores (e.g., glycine-gated or GABA-gated channels). This difference in ionic selectivity reflects underlying differences in how the pore region is constructed. Differences in the pore region determine whether the effect of opening the channel is excitation or inhibition of the postsynaptic cell.

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