Multiple Nicotinic Receptor Subtypes and Their Roles on Individual Neurons

Nicotinic acetylcholine receptors are widely expressed on neurons in both the central and peripheral nervous systems, but until recently, little was known about their physiological significance. This review first summarizes information from molecular cloning studies and heterologous expression systems examining the properties of neuronal nicotinic receptor gene products. It then considers the distribution and properties of native receptors and reports on the multiplicity of subtypes found in the nervous system. The subunit composition of native receptors is shown to be diverse, ranging from homomeric species to those having as many as four kinds of subunits. Individual neurons are found to express more than a single type of nicotinic receptor, and the subtypes can have distinctive locations on the cell surface. Recent evidence is presented for three kinds of functions performed by neuronal nicotinic receptors: presynaptic modulation of neurotransmitter release, postsynaptic mediation of fast, excitatory cholinergic transmission, and correlative signaling involving activation of second messenger cascades. These functions derive in large part from receptor location, ion selectivity, and ability to elevate intracellular calcium levels.