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牛肾上腺嗜铬细胞中的钙通道电流及其受麻醉剂的调节

Calcium channel currents in bovine adrenal chromaffin cells and their modulation by anaesthetic agents.

作者信息

Charlesworth P, Pocock G, Richards C D

机构信息

Department of Physiology, Royal Free Hospital School of Medicine, London, UK.

出版信息

J Physiol. 1994 Dec 15;481 ( Pt 3)(Pt 3):543-53. doi: 10.1113/jphysiol.1994.sp020462.

Abstract
  1. The calcium channel currents of bovine adrenal chromaffin cells were characterized using a variety of voltage pulse protocols and selective channel blockers before examination of their modulation by anaesthetic agents. 2. All the anaesthetics studied (halothane, methoxyflurane, etomidate and methohexitone) inhibited the calcium channel currents in a concentration-dependent manner and increased the rate of current decay. 3. The anaesthetics did not shift the current-voltage relation nor did they change the voltage for half-maximal channel activation derived from analysis of the voltage dependence of the tail currents. None of the anaesthetics appeared to alter the time constant of tail current decay. 4. To complement earlier studies of the inhibitory actions of anaesthetics on K(+)-evoked catecholamine secretion and the associated Ca2+ uptake, the IC50 values for etomidate and methohexitone were determined using a biochemical assay. The IC50 values for anaesthetic inhibition of calcium channel currents corresponded closely with those for inhibition of K(+)-evoked calcium uptake and catecholamine secretion. 5. The inhibitory effect of the volatile anaesthetics and etomidate is best explained by dual action: a reduction in the probability of channel opening coupled with an increase in the rate of channel inactivation. Methohexitone appeared to inhibit the currents by a use-dependent slow block.
摘要
  1. 在研究麻醉剂对牛肾上腺嗜铬细胞钙通道电流的调制作用之前,使用多种电压脉冲方案和选择性通道阻滞剂对其进行了表征。2. 所研究的所有麻醉剂(氟烷、甲氧氟烷、依托咪酯和甲己炔巴比妥)均以浓度依赖性方式抑制钙通道电流,并增加电流衰减速率。3. 麻醉剂既未改变电流-电压关系,也未改变根据尾电流电压依赖性分析得出的通道半数最大激活电压。似乎没有一种麻醉剂改变尾电流衰减的时间常数。4. 为补充早期关于麻醉剂对钾离子诱发的儿茶酚胺分泌及相关钙离子摄取的抑制作用的研究,使用生化测定法确定了依托咪酯和甲己炔巴比妥的半数抑制浓度(IC50)值。麻醉剂抑制钙通道电流的IC50值与抑制钾离子诱发的钙摄取和儿茶酚胺分泌的IC50值密切对应。5. 挥发性麻醉剂和依托咪酯的抑制作用最好用双重作用来解释:通道开放概率降低,同时通道失活速率增加。甲己炔巴比妥似乎通过一种使用依赖性慢阻滞来抑制电流。

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