Dependence of nicotinic acetylcholine receptor recovery from desensitization on the duration of agonist exposure

When subjected to prolonged exposure to nicotinic agonists, nicotinic acety lcholine receptors undergo desensitization, resulting in an inactive recept or that does not allow for the passage of ions. The induction of desensitiz ation of diverse nicotinic acetylcholine receptor subtypes in muscle, gangl ia, or brain is likely to play important modulatory roles in synaptic trans mission. Furthermore, nicotinic receptor desensitization may contribute to behavioral changes in humans or animals subjected to prolonged nicotine exp osure pharmacologically or through the use of tobacco products. We investig ated the recovery from desensitization of muscle-type nicotinic acetylcholi ne receptors in TE671/RD cells induced by exposure to acetylcholine or nico tine. Rates of recovery from desensitization are dependent on the length of agonist exposure and on the agonist used to induce desensitization. Increa sing the time of exposure results in an increase in the time constant of re covery for both agonists. The recovery from nicotine-induced desensitizatio n is consistently faster than the recovery from acetylcholine-induced desen sitization regardless of whether nicotine or acetylcholine is used to asses s levels of desensitization. These findings suggest the existence of more t han one state of receptor desensitization and that nicotinic agonists vary in their efficiency of inducing receptors to states of differing depths of desensitization.