三氧化二砷对豚鼠心室肌细胞钾电流的影响

 目的研究三氧化二砷(arsen ic trioxide,As₂O₃)对豚鼠心室肌细胞钾电流的影响,旨在探讨As₂O₃诱导QT间期延长的离子靶点。方法酶解法分离豚鼠单个心室肌细胞,采用全细胞膜片钳技术深入研究As₂O₃对豚鼠单个心室肌细胞动作电位时程(APD)、延迟整流钾电流(IK)和内向整流钾电流(I_K1)的影响。结果As₂O₃50和100μmol·L^-1分别使APD50从对照组的(273±78)m s增加到(456±35)m s(P<0.01)和(513±41)m s(P<0.01),使APD90从对照组的(286±82)m s增加到(468±36)m s(P<0.01)和(524±40)m s(P<0.01);实验电压为+70 mV时,50和100μmol·L^-1As₂O₃分别使I_K从对照组的(6.7±1.7)pA/pF减少至(4.9±1.6)pA/pF(P<0.05)和(4.5±1.8)pA/pF(P<0.05);在实验电压为-120 mV时,As₂O₃50和100μmol·L^-1分别使IK1从对照组的(-20±5)pA/pF减少至(-13±3)pA/pF(P<0.05)和(-11±2)pA/pF(P<0.05)。结论As₂O₃诱导QT间期延长的离子机制可能与其扰乱了心肌细胞膜离子通道间的平衡,抑制I_K和I_K1,从而导致APD延长有关。

Effects of Arsenic Trioxide on Potassium Current in Isolated Myocytes of Guinea Pig

OBJECTIVE To investigate the effects of arsenic trioxide(As₂O₃) on potassium current in guinea pig ventricular myocytes and to further explore the ionic targets of As₂O₃-induced QT prolongation.METHODS Enzyme digestion was used to isolate single cardiomyocyte of guinea pig.Whole cell patch-clamp technique was utilized to record action potential duration(APD),delayed rectifier potassium current(I_K) and inward rectifier potassium current(I_K1).RESULTS Compared with control groups,APD50 was prolonged from(273±78) ms to(456±35) ms(P<0.01) and(513±41) ms(P<0.01) for 50 and 100 μmol·L^-1 As₂O₃,respectively.APD90 at the same doses of As₂O₃ groups was also prolonged from(286±82) ms to(468±36) ms(P<0.01)and(524±40) ms(P<0.01).At the testing potential of +70 mV,As₂O₃50 and 100 μmol·L^-1 decreased I_K from(6.7±1.7) pA/pF to(4.9±1.6) pA/pF(P<0.05) and(4.5±1.8) pA/pF(P<0.05),respectively.At the testing potential of-120 mV,As₂O₃50 and 100 μmol·L^-1 reduced I_K1 from(-20±5) pA/pF to(-13±3) pA/pF(P<0.05) and(-11±2) pA/pF(P<0.05),respectively.CONCLUSION The ionic mechanism of As₂O₃-induced QT prolongation may be relative to disturbing the normal equilibrium of transmembrane currents(inhibiting I_K and I_K1) and causing prolongation of APD.