TIME-DEPENDENT CHANGES IN CENTRAL NICOTINIC ACETYLCHOLINE CHANNEL KINETICS IN EXCISED PATCHES

The behavior of nicotinic acetylcholine receptor (nAChR) channels in a cutely isolated habenula neurons was examined by rapidly applying nico tinic agonists to outside-out membrane patches. At negative membrane p otentials, applications of 100 mu M nicotine routinely produced macros copic currents due to the opening of a large number of channels. Durin g the continuous application of the agonist, the number of open nAChR channels decreased exponentially, i.e. receptor desensitization. A pro gressive loss in the number of channels contributing to the peak curre nt was observed with time following outside-out patch excision, i.e. r eceptor rundown. In addition to rundown there was a time-dependent inc rease in the rate of desensitization and a concomitant slowing in the rate of recovery from desensitization. The extent of rundown and the c hanges in desensitization were coupled to the time after patch excisio n and were not dependent on ligand activation of nicotinic channels.