%0 Journal Article %A Felix Olale %A Volodymyr Gerzanich %A Alexander Kuryatov %A Fan Wang %A Jon Lindstrom %T Chronic Nicotine Exposure Differentially Affects the Function of Human α3, α4, and α7 Neuronal Nicotinic Receptor Subtypes %D 1997 %J Journal of Pharmacology and Experimental Therapeutics %P 675-683 %V 283 %N 2 %X Because chronic exposure to nicotine and nicotinic drugs might both activate and desensitize nicotinic acetylcholine receptors (AChRs), we sought to determine whether prolonged exposure to nicotine concentrations encountered in tobacco users differentially affects electrophysiological properties of major subtypes of human neuronal nicotinic AChRs. Xenopus laevis oocytes were injected with subunit cRNAs encoding (1) homomeric α7 AChRs, (2) heteromeric α4β2 AChRs and (3) heteromeric α3 AChRs formed from combinations of α3, β2, β4 and α5 cRNAs. Acute activation required micromolar concentrations of nicotine. Chronic exposure to submicromolar concentrations of nicotine irreversibly inactivated many α4β2 AChRs and α7 AChRs but inhibited α3 AChRs much less. Thus, although α3 AChRs are present in the brain in much smaller amounts than are α4β2 AChRs or α7 AChRs, α3 AChRs in brain and autonomic ganglia may be able to play a relatively large role in acute responses to endogenous ACh or subsequent doses of nicotine after chronic exposure to nicotine. The behavioral effects of nicotine may typically reflect the sustained inhibition of α4β2 AChRs and α7 AChRs in combination with the residual susceptibility of α3 AChRs and perhaps some other AChR subtypes for acute activation. Tolerance for nicotine exhibited by tobacco users may reflect the long-term irreversible functional inactivation of α4β2 AChRs and α7 AChRs produced by chronic exposure to nicotine. The American Society for Pharmacology and Experimental Therapeutics %U https://jpet.aspetjournals.org/content/jpet/283/2/675.full.pdf