A quantitative description of the E-4031-sensitive repolarization current in rabbit ventricular myocytes
A quantitative description of the E-4031-sensitive repolarization current in rabbit ventricular myocytes
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DOI：
10.1016/s0006-3495(95)80053-6
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发表时间：
1995-11-01
影响因子：
3.4
通讯作者：
Shrier, A
中科院分区：
文献类型：
--
作者：
Clay, JR;Ogbaghebriel, A;Shrier, A
我们测量了从兔心脏分离的单个心室肌细胞的e -4031敏感复极电流（I-Kr）。本分析的主要目的是描述I-Kr的动力学和离子转移性质。令人惊讶的是，该组分在33-34℃时的最大时间常数为0.8 s，明显大于先前报道的在相似条件下对豚鼠心室肌细胞I-Kr的原始测量值0.18 s。我们分析的主要新颖特征涉及描述动力学电压依赖性的钟形曲线和描述I-Kr活化的s形曲线之间的关系。后者的中点在电压轴上约为+ 10mv，而在电压轴上出现最大时间常数的点为- 30mv。此外，动力学的电压依赖性比激活曲线的陡峭度所预测的要宽得多。综上所述，这些结果构成了一个门控电流悖论，该悖论不能通过在分析中加入快速失活状态来解决。I-Kr的完全激活的电流-电压关系表现出强烈的内向整流，以至于在+30 mV时电流基本为零，即使通道在该电压范围内迅速打开。这一结果与E-4031在动作电位平台期早期缺乏作用是一致的。令人惊讶的是，I-Kr的反转电位与钾离子平衡电位正15 mV相似，这表明在动作电位复极化阶段的后期，该通道携带向内电流。
We have measured the E-4031-sensitive repolarization current (I-Kr) in single ventricular myocytes isolated from rabbit hearts. The primary goal of this analysis was a description of the I-Kr kinetic and ion transfer properties. Surprisingly, the maximum time constant of this component was 0.8 s at 33-34 degrees C, which is significantly greater than the value of 0.18 s previously reported under similar conditions in the original measurements of I-Kr from guinea pig ventricular myocytes. The primary, novel feature of our analysis concerns the relationship of the bell-shaped curve that describes the voltage dependence of the kinetics and the sigmoidal curve that describes the activation of I-Kr. The midpoint of the latter occurred at approximately +10 mV on the voltage axis, as compared to -30 mV for the point on the voltage axis at which the maximum time constant occurred. Moreover, the voltage dependence of the kinetics was much broader than the steepness of the activation curve would predict. Taken together, these results comprise a gating current paradox that is not resolved by the incorporation of a fast inactivated state in the analysis. The fully activated current-voltage relation for I-Kr exhibited strong inward-going rectification, so much so that the current was essentially nil at +30 mV, even though the channel opens rapidly in this voltage range. This result is consistent with the lack of effect of E-4031 on the early part of the plateau phase of the action potential. Surprisingly, the reversal potential of I-Kr was similar to 15 mV positive to the potassium ion equilibrium potential, which indicates that this channel carries inward current during the latter part of the repolarization phase of the action potential.