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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,从-40mV去极化至0mV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(15和30μmol·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(从887ms缩至303ms和223ms,P<0001),延长其平均关闭时间(从923ms延至3884和5443ms,P<0001)并降低其开放概率(从0142降至0031和0025,P<0001)此作用与维拉帕米(15μmol·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
OBJECTIVE: To study the effects of rhynchophylline on the L-type calcium channels in cerebral cortical neurons of acutely isolated Wistar rats. METHODS: Cells were patch-clamped and the L-type calcium channels were activated from -40 mV depolarization to 0 mV. RESULTS: Hypoxia activated the opening of L-type calcium channels in cortical neurons, prolonged the average opening time, shortened the average closure time, and increased the open probability. Rhynchophylline (15 and 30 μmol·L-1) can inhibit the activation of this calcium channel in a hypoxic state in a concentration-dependent manner, shortening its mean opening time (from 887 ms to 303 ms and 223 ms, P<0 001), extending its average closing time (from 923ms to 3884 and 5443ms, P<0001) and reducing its open probability (from 0142 to 0031 and 0025,P <0001) This effect is similar to verapamil (15 μmol·L-1) but slightly weaker. CONCLUSION: Rhynchophylline blocks the L-type calcium channel in cerebral cortex neurons of hypoxic rats, which reduces intracellular calcium overload. This is one of the mechanisms that rhynchophylline can improve the disorder of hypoxic brain metabolism.