Structural and Functional Heterogeneity of Nicotinic Receptors

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Abstract
Three gene families of the ligand-gated ion channel gene superfamily encode proteins which bind cholinergic ligands: (1) nicotinic acetylcholine receptors (AChRs) from skeletal muscle, (2) AChRs from neurons, and (3) neuronal alpha-bungarotoxin-binding proteins (alpha BgtBPs). AChRs from muscles and nerves function as ACh-gated cation channels, but alpha BgtBPs do not appear to function in this way. A family of neuronal AChR subtypes has been characterized using monoclonal antibodies and cDNA probes. Neuronal AChRs exhibit sequence homologies with muscle AChRs, but differ in subunit composition, pharmacological and electrophysiological properties, and, in some cases, apparent functional roles. The genes that encode the subunits of the various purified AChR subtypes have been determined in several cases. Histological localization of AChR subunit mRNAs by in situ hybridization and of subunit proteins by immunohistochemistry is being conducted with increasing resolution. The subunit structure of alpha BgtBP is uncertain, but cDNAs have been identified for two subunits. Sequences of these cDNAs reveal that alpha BgtBPs are members of the ligand-gated ion channel gene family, and suggest that they could function as gated cation channels. Biochemical and molecular genetic approaches to studies of neuronal AChRs and related proteins are merging to provide a detailed description of a complex family of AChRs widely dispersed throughout the nervous system, which are probably important to many activities of the nervous system, but whose functional roles are not yet well characterized.