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目的 研究氯胺酮对豚鼠心室肌细胞膜L 型钙通道的影响 ,探讨氯胺酮在离子通道水平的药理机制。方法 用急性酶解法获得豚鼠的单个心肌细胞 ,在保持电位为 - 40mV、去极化至0mV、波宽为 30 0mS的刺激参数下 ,用标准的全细胞膜片钳技术记录钙电流 ,观察不同浓度的氯胺酮对其影响。结果 用含 1μmol·L-1四乙铵的台氏液灌流时 ,可记录到具有电压和时间依赖性内向的钙电流 ,加入 1μmol·L-1维拉帕米时该电流被迅速消除 ;10 μmol·L-1氯胺酮对钙电流无显著性影响(P >0 0 5 ) ,0 1mmol·L-1和 1mmol·L-1氯胺酮分别使钙电流减少 38 5 9% (P <0 0 5 )和 6 3 89%(P <0 0 5 )。氯胺酮的浓度与钙电流强度呈负相关 (r =- 0 88,P <0 0 1)。 1mmol·L-1氯胺酮使心肌细胞钙电流 电压曲线上移 ,最大激活电压仍为 0mV ,原有的电流 电压依赖特征不变。结论 氯胺酮对心肌细胞膜L 型钙通道具有抑制作用 ,其抑制程度有浓度依赖性。
Objective To investigate the effect of ketamine on L-type calcium channel in guinea pig ventricular myocytes and to explore the pharmacological mechanism of ketamine at ion channel level. Methods Single cardiomyocytes from guinea pigs were obtained by acute enzymatic digestion. Calcium currents were recorded using standard whole-cell patch clamp technique under the stimulation parameters of holding potential of-40mV, depolarization to 0mV and wave width of 30μm. The effects of different concentrations Of ketamine on its impact. Results The currents with voltage-dependent and time-dependent inward currents were recorded when perfused with Tyrosine solution containing 1μmol·L-1 tetraethylammonium. The current was rapidly eliminated when 1μmol·L-1 verapamil was added. 10 There was no significant difference between the two groups (P> 0.05). Ketamine at 0 mmol·L -1 and 1 mmol·L -1 ketamine decreased the calcium current by 38 59% (P 0 05) And 6 3 89% (P <0 05) respectively. Ketamine concentration was negatively correlated with calcium current intensity (r = - 0 88, P <0.01). Ketamine (1 mmol·L-1) up-regulated the calcium current-voltage curve of cardiomyocytes, and the maximum activation voltage was still 0 mV. The original current-voltage dependence characteristics remained unchanged. Conclusion Ketamine has an inhibitory effect on L-type calcium channels in cardiomyocytes, with a concentration-dependent manner.