ACETYLCHOLINE-RECEPTOR DESENSITIZATION INDUCED BY NICOTINE IN RAT MEDIAL HABENULA NEURONS
ACETYLCHOLINE-RECEPTOR DESENSITIZATION INDUCED BY NICOTINE IN RAT MEDIAL HABENULA NEURONS
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DOI：
10.1152/jn.1995.74.1.195
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发表时间：
1995-07-01
影响因子：
2.5
通讯作者：
DANI, JA
中科院分区：
文献类型：
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作者：
LESTER, RAJ;DANI, JA
1.用全细胞膜片钳技术研究了急性分离的内侧缰核（MHb）神经元烟碱乙酰胆碱受体（nAChR）通道的激活和脱敏特性。采用快速溶液交换技术，通过应用已知浓度的烟碱激动剂诱发nAChR介导的电流.在-60 mV的膜电位下，观察到nAChR电流高于约100 nM尼古丁的浓度。在低剂量的激动剂的峰电流振幅与尼古丁浓度的平方成比例，表明通道开放至少需要两个分子的激动剂。根据完整的浓度-反应曲线，估计半数最大nAChR激活所需的尼古丁浓度为77 μ M。在高浓度的尼古丁（300 μ M）的nAChRs的连续激活（2-5秒），电流脱敏迅速和广泛。减敏阶段由两个指数之和描述，时间常数为210和1，435 ms。快速分量占电流减敏阶段的74%。由2秒的300 μ M尼古丁的应用程序诱导的脱敏的恢复也很快，可以合理地用一个单一的指数与时间常数约为800 ms的描述。脱敏和脱敏恢复的时间过程在正膜电位稍慢。低浓度的尼古丁（100 nM-10 μ M）的神经元孵育引起缓慢发展，但明显的脱敏的nAChRs。在这些情况下，通过重复施加较高试验浓度的激动剂脉冲诱导的峰值烟碱电流幅度的降低来评估脱敏。连续暴露于1 μ M尼古丁5分钟可降低乙酰胆碱（30 μ M，1 s）测试反应的幅度，
1. The activation and desensitization properties of nicotinic acetylcholine receptor (nAChR) channels were examined in acutely isolated medial habenula (MHb) neurons using whole cell patch-clamp recordings. nAChR-mediated currents were evoked by applying known concentrations of nicotinic agonists using rapid solution exchange techniques.2. At a membrane potential of -60 mV, nAChR currents were observed above a concentration of approximate to 100 nM nicotine. The peak current amplitude at low doses of agonist was proportional to the square of the concentration of nicotine, indicating that at least two molecules of agonist were required for channel opening. The concentration of nicotine required for half-maximal nAChR activation was estimated as 77 mu M from a complete concentration-response curve.3. During the continuous activation (2-5 s) of nAChRs by high concentrations of nicotine (300 mu M), the current desensitized rapidly and extensively. The desensitization phase was described by the sum of two exponentials, with time constants of 210 and 1,435 ms. The fast component comprised 74% of the desensitizing phase of the current. Recovery from desensitization induced by 2-s applications of 300 mu M nicotine was also fast and could be reasonably well described by a single exponential with a time constant of approximate to 800 ms. Both the time courses of desensitization and recovery from desensitization were slightly slower at positive membrane potentials.4. Incubation of neurons with low concentrations of nicotine (100 nM-10 mu M) caused a slowly developing but pronounced desensitization of the nAChRs. In these cases desensitization was assessed from the reduction in the amplitude of the peak nicotinic current induced by repetitively applied pulses of a higher test concentration of agonist. A 5-min continuous exposure to 1 mu M nicotine reduced the amplitude of the acetylcholine (30 mu M, 1 s) test response to