CNS localization of neuronal nicotinic receptors

Abstract

Nicotinic acetylcholine receptors (nAChRs) are members of the Cys-loop superfamily of pentameric ligand-gated ion channels, which include GABA (A and C), serotonin, and glycine receptors. Currently, 12 neuronal nAChR subunits have been identified (alpha2-10 and beta2-4) and are generally grouped into alpha subunits, which contain two adjacent cysteine residues essential for ACh binding, and beta subunits, which lack these residues. The majority of neuronal nAChRs fall into two categories: those that bind agonist with high affinity (nM concentrations); and those that bind with lower affinity (microM concentrations). The low-affinity receptors are presumably homomeric alpha7 receptors that are alpha-bungarotoxin sensitive, whereas alpha4beta2 nAChRs account for >90% of the high-affinity nicotinic receptors in the brain (Whiting and Lindstrom, 1986). Their physiological contributions to neurotransmission, signaling, and behavior are not completely understood. Precise mapping of subcellular and neuroanatomical localizations of neuronal nAChR subunits will help elucidate the physiological role of neuronal nAChRs and their role in nicotine addiction.