EFFECTS OF ALCOHOLS AND VOLATILE ANESTHETICS ON THE ACTIVATION OF NICOTINIC ACETYLCHOLINE-RECEPTOR CHANNELS

The n-alcohols butanol through nonanol and the volatile anesthetic eth er increase the frequency of bursts of nicotinic acetylcholine (ACh) r eceptor channels induced by low concentrations of agonists. For exampl e, 10 mM butanol increases the burst frequency induced by 0.2 mu M ACh (a full agonist) and 1 mu M decamethonium (a partial agonist) by 1.6- fold and 2.7-fold, respectively. An increase in burst frequency could arise from effects of the drug on agonist binding, channel gating, or desensitization. To distinguish among these alternatives, we measured the current response to rapid application of saturating concentrations of agonists. We found that 10 mM butanol increases the peak current i nduced by 100 mu M decamethonium by 2-fold. In addition, 20 mM butanol and 3 mM pentanol both decrease the onset time of the current respons e to 10 mM ACh by about 40%. In contrast, ether does not increase the current response to 100 mu M decamethonium and does not significantly change the onset time for 10 mM ACh. Neither ether nor butanol changes the degree of steady state desensitization induced by 0.2 mu M ACh. W e conclude that butanol and pentanol increase burst frequency by incre asing the channel opening rate, whereas ether does so by increasing th e agonist binding affinity of the ACh receptor.