Effects of alcohols and volatile anesthetics on the activation of nicotinic acetylcholine receptor channels.
Effects of alcohols and volatile anesthetics on the activation of nicotinic acetylcholine receptor channels.
复制标题
酒精和挥发性麻醉剂对烟碱乙酰胆碱受体通道激活的影响。
作者：
Y. Liu;J. Dilger;A. Vidal
正醇、正丁醇、正庚醇和挥发性麻醉醚增加了低浓度激动剂引起的烟碱型乙酰胆碱(ACh)受体通道爆发的频率。例如，10 mM丁醇可使0.2微米ACh(完全激动剂)和1微米十美托宁(部分激动剂)诱发的猝发频率分别增加1.6倍和2.7倍。猝发频率的增加可能源于药物对激动剂结合、通道门控或脱敏的影响。为了区分这些替代方案，我们测量了快速应用饱和浓度激动剂的电流反应。我们发现，10 mM的丁醇使100微米的敌草胺诱发的峰电流增加2倍。此外，20 mM丁醇和3 mM戊醇均可将电流对10 mM ACh的反应起始时间缩短约40%。相反，乙醚不会增加电流对100微米十氯甲烷的响应，也不会显著改变10 mM ACh的起效时间。乙醚和正丁醇都不能改变0.2微米ACh引起的稳态脱敏程度。我们的结论是，丁醇和戊醇通过增加通道开放速率来增加猝发频率，而乙醚通过增加ACh受体的激动剂结合亲和力来增加猝发频率。
The n-alcohols butanol through nonanol and the volatile anesthetic ether increase the frequency of bursts of nicotinic acetylcholine (ACh) receptor channels induced by low concentrations of agonists. For example, 10 mM butanol increases the burst frequency induced by 0.2 microM ACh (a full agonist) and 1 microM 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 induced by 100 microM decamethonium by 2-fold. In addition, 20 mM butanol and 3 mM pentanol both decrease the onset time of the current response to 10 mM ACh by about 40%. In contrast, ether does not increase the current response to 100 microM 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 microM ACh. We conclude that butanol and pentanol increase burst frequency by increasing the channel opening rate, whereas ether does so by increasing the agonist binding affinity of the ACh receptor.