Background-The ultrarapid outward current IKur is a major repolarizing current in human atrium and a potential target for treating atrial arrhythmias. The effects of selective block of IKur by low concentrations of 4-...Background-The ultrarapid outward current IKur is a major repolarizing current in human atrium and a potential target for treating atrial arrhythmias. The effects of selective block of IKur by low concentrations of 4-aminopyridine of or the biphenyl derivative AVE 0118 were investigated on right atrial action potentials (APs) in trabeculae from patients in sinus rhythm(SR) or chronic atrial fibrillation(AF). Methods and Results-AP duration at 90%repolarization (APD90)-was shorter in AF than in SR (300±16 ms, n=6, versus 414±10 ms, n=15), whereas APD 20 was longer (35±9 ms in AF versus 5±2 ms in SR, P< 0.05). 4-Aminopyridine (5 μmol/L) elevated the plateau to more positive potentials from-21±3 to-6±3 mV in SR and 0±3 to+12±3 mV in AF. 4-Aminopyridine reversibly shortened APD90 from 414±10 to 350±10 ms in SR but prolonged APD90 from 300±16 to 320±13 ms in AF. Similar results were obtained with AVE 0118 (6 μmol/L). Computer simulations of IKur block in human atrial APs predicted secondary increases in ICa.L and in the outward rectifiers IKr and IKs, with smaller changes in AF than SR. The indirect increase in ICa.L was supported by a positive inotropic effect of 4-aminopyridine without direct effects on ICa.L in atrial but not ventricular preparations. In accordance with the model predictions, block of IKr with E-4031 converted APD shortening effects of IKur block in SR into AP prolongation. Conclusions-Whether inhibition of IKur prolongs or shortens APD depends on the disease status of the atria and is determined by the level of electrical remodeling.展开更多
目的通过膜片钳技术研究大鼠心房肌细胞延迟整流钾通道(IKur)的电流特性,以及伊布利特对大鼠心房肌细胞IKur的影响。方法大鼠离体心脏行主动脉插管,应用Langendorff装置恒流灌流,依次用无钙台氏液、Ⅱ型胶原酶,分离出大鼠单个心房肌细胞...目的通过膜片钳技术研究大鼠心房肌细胞延迟整流钾通道(IKur)的电流特性,以及伊布利特对大鼠心房肌细胞IKur的影响。方法大鼠离体心脏行主动脉插管,应用Langendorff装置恒流灌流,依次用无钙台氏液、Ⅱ型胶原酶,分离出大鼠单个心房肌细胞,采用标准的全细胞膜片钳技术记录IKur的电流图,计算电压电流曲线(I-V曲线),采用伊布利特配成2μg/L溶液灌流3 min,记录IKur。结果大鼠心房肌细胞超速激活的IKur电流特性:激活迅速,几乎无延迟现象,失活缓慢,峰电流呈现出外向整流特征,该电流约在-20 m V被激活,峰电流存在明显的电压依赖性,峰值(2.01±0.27)p A/p F。对于去极化至-10 m V^+20 m V时,伊布利特没有对IKur产生影响;伊布利特降低了+30 m V^+50 m V时IKur的电流密度数值,但无统计学意义。结论大鼠心房肌细胞的IKur电流特性:超速激活,无延迟现象,失活缓慢,峰电流呈现出外向整流特征,表现为显著的快速全动作电位时程的外向整流特征。2μg/L伊布利特灌流没有对IKur产生影响。展开更多
文摘Background-The ultrarapid outward current IKur is a major repolarizing current in human atrium and a potential target for treating atrial arrhythmias. The effects of selective block of IKur by low concentrations of 4-aminopyridine of or the biphenyl derivative AVE 0118 were investigated on right atrial action potentials (APs) in trabeculae from patients in sinus rhythm(SR) or chronic atrial fibrillation(AF). Methods and Results-AP duration at 90%repolarization (APD90)-was shorter in AF than in SR (300±16 ms, n=6, versus 414±10 ms, n=15), whereas APD 20 was longer (35±9 ms in AF versus 5±2 ms in SR, P< 0.05). 4-Aminopyridine (5 μmol/L) elevated the plateau to more positive potentials from-21±3 to-6±3 mV in SR and 0±3 to+12±3 mV in AF. 4-Aminopyridine reversibly shortened APD90 from 414±10 to 350±10 ms in SR but prolonged APD90 from 300±16 to 320±13 ms in AF. Similar results were obtained with AVE 0118 (6 μmol/L). Computer simulations of IKur block in human atrial APs predicted secondary increases in ICa.L and in the outward rectifiers IKr and IKs, with smaller changes in AF than SR. The indirect increase in ICa.L was supported by a positive inotropic effect of 4-aminopyridine without direct effects on ICa.L in atrial but not ventricular preparations. In accordance with the model predictions, block of IKr with E-4031 converted APD shortening effects of IKur block in SR into AP prolongation. Conclusions-Whether inhibition of IKur prolongs or shortens APD depends on the disease status of the atria and is determined by the level of electrical remodeling.
文摘目的通过膜片钳技术研究大鼠心房肌细胞延迟整流钾通道(IKur)的电流特性,以及伊布利特对大鼠心房肌细胞IKur的影响。方法大鼠离体心脏行主动脉插管,应用Langendorff装置恒流灌流,依次用无钙台氏液、Ⅱ型胶原酶,分离出大鼠单个心房肌细胞,采用标准的全细胞膜片钳技术记录IKur的电流图,计算电压电流曲线(I-V曲线),采用伊布利特配成2μg/L溶液灌流3 min,记录IKur。结果大鼠心房肌细胞超速激活的IKur电流特性:激活迅速,几乎无延迟现象,失活缓慢,峰电流呈现出外向整流特征,该电流约在-20 m V被激活,峰电流存在明显的电压依赖性,峰值(2.01±0.27)p A/p F。对于去极化至-10 m V^+20 m V时,伊布利特没有对IKur产生影响;伊布利特降低了+30 m V^+50 m V时IKur的电流密度数值,但无统计学意义。结论大鼠心房肌细胞的IKur电流特性:超速激活,无延迟现象,失活缓慢,峰电流呈现出外向整流特征,表现为显著的快速全动作电位时程的外向整流特征。2μg/L伊布利特灌流没有对IKur产生影响。
