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Volume 17, Number 15, Issue of August 1, 1997 pp. 5747-5759
Copyright ©1997 Society for Neuroscience

Influence of Subunit Composition on Desensitization of Neuronal Acetylcholine Receptors at Low Concentrations of Nicotine

Received Dec. 30, 1996; revised April 18, 1997; accepted May 19, 1997.

Catherine P. Fenster1, 2, M. Felicia Rains1, Brett Noerager2, Michael W. Quick1, 2, and Robin A. J. Lester1, 2

Departments of 1 Neurobiology and 2 Physiology and Biophysics, University of Alabama at Birmingham, Birmingham, Alabama 35294

The influence of alpha  and beta  subunits on the properties of nicotine-induced activation and desensitization of neuronal nicotinic acetylcholine receptors (nAChRs) expressed in Xenopus oocytes was examined. Receptors containing alpha 4 subunits were more sensitive to activation by nicotine than alpha 3-containing receptors. At low concentrations of nicotine, nAChRs containing beta 2 subunits reached near-maximal desensitization more rapidly than beta 4-containing receptors. The concentration of nicotine producing half-maximal desensitization was influenced by the particular alpha  subunit expressed; similar to results for activation, alpha 4-containing receptors were more sensitive to desensitizing levels of nicotine than alpha 3-containing receptors. The alpha  subunit also influenced the rate of recovery from desensitization; this rate was approximately inversely proportional to the apparent nicotine affinity for the desensitized state. The homomeric alpha 7 receptor showed the lowest sensitivity to nicotine for both activation and desensitization; alpha 7 nAChRs also demonstrated the fastest desensitization kinetics. These subunit-dependent properties remained in the presence of external calcium, although subtle, receptor subtype-specific effects on both the apparent affinities for activation and desensitization and the desensitization kinetics were noted. These data imply that the subunit composition of various nAChRs determines the degree to which receptors are desensitized and/or activated by tobacco-related levels of nicotine. The subtype-specific balance between receptor activation and desensitization should be considered important when the cellular and behavioral actions of nicotine are interpreted.

Key words: nicotinic receptor subtypes; nicotine addiction; ion channel; CNS; desensitization; regulation; Xenopus oocytes; calcium ions; synaptic transmission




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