Neuronal Nicotinic Receptors: One Hundred Years of Progress

AbstractNeuronal nicotinic cholinergic receptors mediate the actions of acetylcholine in ganglia and the CNS. These receptors are pentameric proteins formed from combinations of 12 different subunits. Thus, this family of receptors consists of multiple subtypes defined by their subunit composition. All of the receptors are ligand‐gated cation channels that pass sodium, potassium and calcium, but the different subtypes have different biophysical and pharmacological characteristics. These receptors are located on the axons of catecholamine, GABA, acetylcholine and glutamate neurons, so they can influence a large number of diverse functions in the nervous system. In addition to mediating the essential actions of endogenous acetylcholine, these receptors are the primary target of nicotine, the addictive agent in tobacco. Thus, these receptors are directly related to the single most preventable cause of premature morbidity and mortality. In this chapter, we review some of the fundamental aspects of these receptors, with emphasis on the differences in pharmacology among the receptor subtypes and their unusual regulation by exposure to nicotine.