OUTWARD CURRENTS UNDERLYING REPOLARIZATION IN HUMAN ATRIAL MYOCYTES
OUTWARD CURRENTS UNDERLYING REPOLARIZATION IN HUMAN ATRIAL MYOCYTES
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DOI：
10.1016/s0008-6363(95)00014-3
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发表时间：
1995-07-01
影响因子：
10.8
通讯作者：
GILES, WR
中科院分区：
文献类型：
--
作者：
FIREK, L;GILES, WR
目的：确定人心房肌细胞动作电位平台处激活的外向钾(K+)电流的类型，并与已从人cDNA库中克隆的K+通道的已发表数据进行比较。用酶法分离单个心肌细胞，应用全细胞电压和电流钳记录技术。结果：大多数细胞的外向K+电流由瞬时和持续(非失活)成分组成。4-氨基吡啶(4-AP，50muM)通过阻断非钙非依赖性瞬时外向钾电流(I-t)，使动作电位变宽，平台高度增加。暂态分量和基座分量也可以通过两种脉冲电压钳制方案进行失活：400ms去极化预脉冲(-80~0 mV)完全失活暂态分量。相反，即使施加非常长(2500毫秒)的预脉冲，基座组件的失活也不完全。大多数细胞K+电流失活的时间过程可用两个指数函数之和来描述。在+10 mV和+40 mV之间的膜电压下，两个失活过程中较快的一个与电压无关。还研究了[K+](0)对I-t恢复动力学(再活化)的依赖关系。当[K+](0)从5.4 mm降至1.0 mm时，再活化速度显著减慢。结论：这些结果为早期和晚期复极的离子机制(S)提供了额外的信息，并使电生理上可存活的人心房细胞的发现与有关人心脏钾电流分子生物学的最新信息相关联。
Objective: The goals of this study were to identify the types of outward potassium (K+) currents that are activated at membrane potentials corresponding to the plateau of the action potential in human atrial myocytes, and to compare their properties with published data describing the K+ channels which have been cloned from a human cDNA library.Methods: Specimens of right atrial appendages were obtained from patients undergoing cardiac surgery. Single myocytes were isolated enzymatically and whole cell voltage- and current-clamp recording techniques were applied.Results: The outward K+ current in most cells consisted of transient and sustained (non-inactivating) components. 4-Aminopyridine (4-AP, 50 mu M) broadened the action potential and increased the plateau height by blocking a Ca2+-independent transient outward K+ current(I-t). The transient and the pedestal components could also be separated by using two pulse voltage-clamp protocols to inactivate them: the transient component was inactivated completely by 400 ms depolarizing pre-pulses (-80 to 0 mV). In contrast, the inactivation of the pedestal component was not complete even when very long (2500 ms) pre-pulses were applied. The time-course of inactivation of the K+ currents in most cells could be described mathematically by the sum of two exponential functions. The faster of the two processes underlying inactivation was voltage-independent for membrane voltages between + 10 and +40 mV. The dependence of the recovery kinetics (reactivation) of I-t on [K+](0) was also studied. When [K+](0) was reduced from 5.4 to 1.0 mM, reactivation slowed significantly. In a small fraction of atrial cells, a slowly activating delayed rectifier current was also identified.Conclusions: These results provide additional information concerning the ionic mechanism(s) for early and late repolarization, and they allow findings from electrophysiologically viable human atrial cells to be related to recent information regarding the molecular biology of potassium currents in human heart.