Evans M L, Carpenter D O
Wadsworth Center for Laboratories and Research, New York State Department of Health, University at Albany 12237.
Brain Res. 1989 Aug 28;495(2):309-18. doi: 10.1016/0006-8993(89)90223-0.
The kinetics of desensitization of acetylcholine-evoked Cl conductance increased response of Aplysia RC neurons of the abdominal ganglion were studied under voltage-clamp conditions for comparison with results of similar studies on acetylcholine Na and K responses. The response evoked by acetylcholine on RC neurons was an outward current at resting potential (about -45 mV) that reversed at about -65 mV and was blocked by D-tubocurarine and strychnine but not hexamethonium and was not activated by arecoline. From the current-voltage relation this response can be ascribed to a pure conductance increase to Cl. The apparent KD was 40.6 microM. Upon prolonged exposure to acetylcholine the response peaked within 200-400 ms, and then decayed to a plateau current in the continued presence of the agonist. The peak and plateau currents reversed at the same potential, indicating that there had not been significant redistribution of Cl. The current decay in every cell was best fit by a double exponential function plus a constant, and the average time constants were tau fast = 1.8 +/- 0.2 s and tau slow = 16.2 +/- 1.0 s. Both components were slowed by cooling. While tau fast did not change with dose, tau slow increased with dose. Both components accelerated with hyperpolarization and upon application of trifluoperazine (2 microM). These results are consistent with the interpretation that desensitization of the acetylcholine Cl response is composed of two independent processes. This conclusion is the same as that derived from studies of the acetylcholine Na and K responses, and is in general consistent with desensitization being a property of a common acetylcholine receptor, and independent of the ionic selectivity of the associated channel. There are, however, significant differences in voltage, temperature and trifluoperazine dependence of the two components of the three ionic responses which may reflect influence of the different ion channels and/or transduction mechanisms.
在电压钳制条件下，研究了腹神经节的海兔RC神经元中乙酰胆碱诱发的氯离子电导增加反应的脱敏动力学，以便与关于乙酰胆碱钠和钾反应的类似研究结果进行比较。乙酰胆碱对RC神经元诱发的反应是静息电位（约-45 mV）时的外向电流，在约-65 mV时反转，可被筒箭毒碱和士的宁阻断，但不能被六甲铵阻断，且不能被槟榔碱激活。从电流-电压关系来看，该反应可归因于氯离子的纯电导增加。表观解离常数KD为40.6微摩尔。长时间暴露于乙酰胆碱后，反应在200-400毫秒内达到峰值，然后在激动剂持续存在的情况下衰减至平台电流。峰值电流和平台电流在相同电位反转，表明氯离子没有显著的重新分布。每个细胞中的电流衰减最适合用双指数函数加一个常数来拟合，平均时间常数为快速时间常数tau fast = 1.8 +/- 0.2秒，慢速时间常数tau slow = 16.2 +/- 1.0秒。两个成分都因冷却而减慢。虽然快速时间常数不随剂量变化，但慢速时间常数随剂量增加。两个成分都随着超极化和应用三氟拉嗪（2微摩尔）而加速。这些结果与乙酰胆碱氯离子反应的脱敏由两个独立过程组成的解释一致。这一结论与从乙酰胆碱钠和钾反应研究中得出的结论相同，并且总体上与脱敏是常见乙酰胆碱受体的一种特性且与相关通道的离子选择性无关一致。然而，三种离子反应的两个成分在电压、温度和三氟拉嗪依赖性方面存在显著差异，这可能反映了不同离子通道和/或转导机制的影响。
