氟卡尼电压和频率依赖性抑制豚鼠心房细胞迟发性外向钾电流(英文)

Frequency- and voltage-dependent inhibition of delayed outward potassium current by flecainide in isolated atrial cell of guinea pig heart

本文用单细胞钳法研究了氟卡尼(flecainide,F1e)对豚鼠心房单细胞膜电流的影响,发现Fle频率依鞍性延长动作电位时程,并且浓度和频率依赖性减低迟发性外向钾电流和尾电流,Fle对保持电流作用不显著,Fle抗房性心律失常机制是电压依赖性抑制外向钾电流,Fle显著影响复极过程,故不符合I_c类抗心律失常药物。

Effects of flecanide (Fle) on membrane currents were studied using an isolated single atrial cell from guinea pig hearts. The tight-seal cell clamp technique was used. In the current clamp condition, Fle prolonged singnificantly the atrial action potential (APD) with frequency dependence. Delayed outward K+ current and outward tail current w re specifically inhibited by Fle in a frequency-and concentration-dependent fashion. Fle inhibited Ik more strongly as the membrane potential became more positive from -10 mV to +60 mV. The value of It was attenuated to 973 pA from 1105 pA of control and the value of tail current was reduced to 113 pA from 288 pA of control at 60 mV. The drug did not affect the holding current. The effects of Fre on the action potential and transmembrane ionic currents strongly suggested that the main mechanism of action of this agent was to inhibit the voltage-dependent potassium current. In the voltage clamp condition, Fre affected neither the conventional L type Ca2+ current nor the Ik1 current significantly. Our research proved that Fre was not completely consistent with the class Ic agents, because Fre could markedly increase the APD in the experiment.