Dependence of nicotinic acetylcholine receptor recovery from desensitization on the duration of agonist exposure.
When subjected to prolonged exposure to nicotinic agonists, nicotinic acetylcholine receptors undergo desensitization, resulting in an inactive receptor that does not allow for the passage of ions. The induction of desensitization of diverse nicotinic acetylcholine receptor subtypes in muscle, ganglia, or brain is likely to play important modulatory roles in synaptic transmission. Furthermore, nicotinic receptor desensitization may contribute to behavioral changes in humans or animals subjected to prolonged nicotine exposure pharmacologically or through the use of tobacco products. We investigated the recovery from desensitization of muscle-type nicotinic acetylcholine receptors in TE671/RD cells induced by exposure to acetylcholine or nicotine. Rates of recovery from desensitization are dependent on the length of agonist exposure and on the agonist used to induce desensitization. Increasing the time of exposure results in an increase in the time constant of recovery for both agonists. The recovery from nicotine-induced desensitization is consistently faster than the recovery from acetylcholine-induced desensitization regardless of whether nicotine or acetylcholine is used to assess levels of desensitization. These findings suggest the existence of more than one state of receptor desensitization and that nicotinic agonists vary in their efficiency of inducing receptors to states of differing depths of desensitization.
Reitstetter
R
R
Department of Physiology, University of Arizona College of Medicine, Tucson, Arizona, USA.
Lukas
R J
RJ
Gruener
R
R
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology; D009132:Muscles / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009538:Nicotine / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D051381:Rats; D011978:Receptors, Nicotinic / Q000187:drug effects* / Q000502:physiology; D013997:Time Factors
D007473:Ion Channels; D018722:Nicotinic Agonists; D011978:Receptors, Nicotinic; D009538:Nicotine; D000109:Acetylcholine