Effects of alcohols and volatile anesthetics on the activation of nicotinic acetylcholine receptor channels. Mol Pharmacol 45:1235–1241

The n-alcohols butanol through nonanol and the volatile anes-thetic ether increase the frequency of bursts of nicotinic acetyl-choline (ACh) receptor channels induced by low concentrations of agonists. For example, 1 0 m butanol increases the burst frequency induced by 0.2 LM ACh (a full agonist) and 1 M decamethonium (a partial agonist) by 1.6-fold and 2.7-fold, re-spectively. An increase in burst frequency could arise from effects of the drug on agonist binding, channel gating, or desen-sitization. To distinguish among these alternatives, we measured the current response to rapid application of saturating concen-trations of agonists. We found that 1 0 m butanol increases the peak current induced by 100 M decamethonium by 2-fold. In addition, 20 mM butanol and 3 mi pentanol both decrease the onset time of the current response to 1 0 m ACh by about 40%. In contrast, ether does not increase the current response to 10