氯胺酮对豚鼠心室肌细胞膜L-型钙通道的影响

Effect of ketamine on L-type calcium channels in isolated cardiomyocytes of guinea pig

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 observe the effect of ketamine on L-type calcium channel in isolated ventricular myocytes Methods Single ventricular cell of guinea pig was obtained by an enzymatic dissociation method Under the condition of holding potential -40mV and depolarizing to 0mV with duration of 30ms,the whole-cell pacth clamp recording technique was used to record the change of calcium current (ICa) following the administration of ketamine at 10-1 000μmol·L -1 Results The verapamil-sensitive L-type calcium inward current was recorded in the ventricular myocytes Ketamine 10μmol·L -1 did not change the peak ICa(P>0 05),ketamine 100 μmol·L -1 and 1000 μmol·L -1 decreased peak ICa by 38 59% and 63 89% ,respectively (P<0 05) A significant negative correlation existed between the concentration of ketamine and ICa(r=0 88,P<0 01) The current-voltage curves of ICa was shifted above with the peak Ica being elicited at the potential (0mV) Conclusions Ketamine inhibites the L-type calcium channels of ventricular myocytes in a good dose-response manner