【摘要】 目的研究卡维地洛对大鼠心室肌细胞L型钙电流(ICa,L)的影响,探讨卡维地洛在离子通道水平的药理机制。方法用急性酶解法获得大鼠单个心室肌细胞,用标准全细胞膜片钳技术记录ICa,L,观察不同浓度卡维地洛对ICa,L的影响。结果①卡维地洛呈浓度依赖性抑制ICa,L,1μmol/L卡维地洛能使心肌细胞ICa,L电流-电压关系曲线明显上移,峰电流密度减少(7.80±0.65pA/pFvs4.89±0.52pA/pF,n=10,P<0.05),但激活电位、峰电位和翻转电位无明显改变。②卡维地洛能使ICa,L失活曲线明显左移,但对ICa,L激活和复活曲线无明显影响。③0.1μmol/L卡维地洛对钙电流无明显影响,但可以明显阻断异丙肾上腺素增加钙电流效应。同时,卡维地洛对钙电流的抑制效应不能被哌唑嗪和普奈洛尔阻断。结论卡维地洛呈浓度依赖性地抑制心室肌细胞L型钙通道。更多还原

【Abstract】 Objective To determine the effect and mechanism of carvedilol on L-type calcium current (I_ Ca,L). Methods Whole-cell patch clamp recording technique was used to record I_ Ca,L in single cells isolated rat ventricular myocytes. Results The nifedipine-sensitive L-type calcium inward current was recorded in the rat ventricular myocytes. Carvedilol decreased the calcium channel current in a dose-dependent and voltage-dependent manner in ventricular myocytes of rats. ①The current-voltage curve was shifted upwards, in which active potential,peak potential and reverse potential had no significant changes. ②The inactivation curve was shifted to more negative potential, but the activation curve and the recovery curve were not altered. ③Carvedilol blocked the effect of 1μmol/L isoproterenol which increased calcium current. Carvedilol at lower concentration (<0.1μmmol/L ) did not affect I_ Ca,L, but it decreased the increase in I_ Ca,L induced by isoproterenol. Prazonsin and propranolol couldn’t block the higher concentration (>0.5μmmol/L ) of carvedilol-induced reduction of I_ Ca,L. Conclusion Carvedilol concentration-dependently decreases calcium channel current in ventricular myocytes of rat.更多还原