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钩藤碱对急性低氧大鼠大脑皮层神经元L-型钙通道的影响

开丽, 王中峰, 薛春生   

  1. 1. 第三军医大学药理教研室, 重庆 400038;
    2. 第三军医大学生理教研室, 重庆 400038;
    3. 重庆医科大学药理教研室, 重庆 400046
  • 收稿日期:1997-07-15 修回日期:1998-02-24 出版日期:1998-12-15 发布日期:1998-12-15

Effects of Rhynchophylline on L-type Calcium Channels in Isolated Rat Cortical Neurons During Acute Hypoxia

Li Kai, Zhong-Feng Wang, Chun-Sheng Xue   

  1. 1. Department of Pharmacology, Third Military Medical University, Chongqing 400038;
    2. Department of Physiology, Third Military Medical University, Chongqing 400038;
    3. Department of Pharmacology, Chongqing University of Medical Sciences, Chongqing 400046
  • Received:1997-07-15 Revised:1998-02-24 Online:1998-12-15 Published:1998-12-15

摘要: 目的: 研究钩藤碱对急性分离的Wistar大鼠大脑皮层神经元低氧状态下L-型钙通道的作用。方法: 细胞贴附膜片钳技术, -40 mV去极化至0 mV激活L-型钙通道。结果: 低氧可激活皮层神经元L-型钙通道开放, 使平均开放时间延长, 平均关闭时间缩短,开放概率增加。钩藤碱(1530 μmol·L-1)可浓度依赖性抑制低氧状态下此钙通道的激活, 缩短其平均开放时间(8.87 ms缩至3.03 ms2.23 ms, P<0.001), 延长其平均关闭时间(9.23 ms延至38.8454.43 ms, P<0.001)并降低其开放概率(0.142降至0.0310.025, P<0.001)此作用与维拉帕米(15 μmol·L-1)相似, 但稍弱。结论: 钩藤碱对低氧大鼠大脑皮层神经元L-型钙通道有阻滞作用, 从而降低细胞内钙超载, 此为钩藤碱改善低氧性脑代谢紊乱的机制之一。

关键词: 膜片钳, 皮层神经元, 钙通道, 钩藤碱, 低氧

Abstract: Aim: To study the effects of rhynchophylline (Rhy) on the L-type calcium channels in freshly dissociated cortical neurons of Wistar rats during acute hypoxia. Methods: Cell-attached configuration of patch clamp technique. L-type calcium channel was activated by stepping from-40 mV to 0 mV. Results: The results showed that the L-type calcium channels of cortical neurons were activated by acute hypoxia. The mean open time of the channel was increased, the mean close time decreased and the open-state probability raised during acute hypoxia. Rhy (15 and 30 μmol·L-1) in concentration dependent manner blocked activity of the channels. The drug shortened the mean open time of the channels from 8.87 ms to 3.03 ms and 2.23 ms (P<0.001), prolonged the mean close time from 9.23 ms to 38.84 ms and 54.43 ms (P<0.001), and decreased the open-state probability from 0.142 to 0.031 and 0.025 (P<0.001) under the hypoxia condition, respectively. The effects of Rhy were similar to but weaker than those of verapamil (15 μmol·L-1). Conclusion: The study confirmed that Rhy has the blockade effects on L-type calcium channels in cortical neurons of rats during hypoxia, by which it protects the brain from hypoxic injury.

Key words: Patch clamp, Cortical neuron, Calcium, Ion channel, Rhynchophylline, Hypoxia

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