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目的探讨多非力特对心肌细胞电生理作用的特点。方法(1)应用膜片钳全细胞技术记录单个豚鼠心室肌细胞膜延迟整流性钾流(IK),观察不同浓度多非力特对IK的影响,并探讨IK的快速激活成分(IKr)的电生理特性。(2)标准微电极技术记录豚鼠右室乳头肌细胞动作电位,观察不同浓度多非力特灌流前后动作电位各参数的变化。结果(1)多非力特0.01～0.5μmol/L呈浓度依赖性抑制IK的时间依赖性外向钾流(IK.time)和尾电流(IK.tail),但浓度再增大至1μmol/L后,此抑制作用趋于最大。对-20mV钳制电压下IK.time、IK.tail的抑制程度比+50mV时更明显(P<0.05或0.01)。(2)通道动力学分析发现,多非力特1μmol/L使IK.tail快失活过程消失,慢失活时间常数无明显变化(P>0.05)。(3)多非力特敏感的电流成分在-40mV开始呈电压依赖性快速激活,峰值电压为0,开始出现内向整流,其IK.tail也呈电压依赖,无内向整流,但膜电位达+20mV后达饱和,以上均符合IKr的特点。(4)多非力特对动作电位的影响:0.5和1.0μmol/L浓度下可使动作电位时程(APD30、APD90)均明显延长(P<0.05或<0.01),且呈反转频率依赖性。结论多非力特对IK的作用符合特异性IKr阻滞剂的特点,并呈反转频率依赖性延长APD,是其抗心律失常作用的电生理基础。
Objective To investigate the characteristics of electrophysiological effects of duloxetol on cardiomyocytes. Methods (1) Whole-cell patch-clamp technique was used to record the delayed rectifier potassium current (IK) of single guinea pig ventricular myocytes. The effects of different concentrations of dliproxil on IK were observed and the electrophysiological characteristics of IK (IKr) characteristic. (2) Standard microelectrode technique was used to record the action potentials of right ventricular papillary muscle cells in guinea pigs. The changes of action potentials before and after multi-non-special perfusion were observed. Results (1) The dose-dependent inhibition of IK and IK.tail at concentrations of 0.01-0.5 μmol / L with dofetilide increased the IK.tail concentration to 1 μmol / L , This inhibition tends to be the largest. Inhibition of IK.time and IK.tail at -20 mV clamping voltage was more pronounced than at +50 mV (P <0.05 or 0.01). (2) The kinetic analysis of channels showed that the fast inactivation of IK.tail disappeared with 1 μmol / L of duloxetine, and there was no significant change in the time constant of slow inactivation (P> 0.05). (3) Dofetil-sensitive current components began to rapidly activate in a voltage-dependent manner at -40mV with a peak voltage of 0 and an inward rectification began to occur. The IK.tail was also voltage-dependent with no inward rectification but the membrane potential reached +20 mV After up to saturation, the above are in line with the characteristics of IKr. (4) The effect of dofetilide on action potential: The action potential duration (APD30, APD90) were significantly prolonged (P <0.05 or <0.01) at 0.5 and 1.0 μmol / L concentrations, and in a reversal frequency-dependent manner . CONCLUSIONS: The effect of dofetilide on IK is consistent with the characteristics of specific IKr blockers and reversing the frequency-dependent prolongation of APD, which is the electrophysiological basis of its anti-arrhythmic effect.