Time-dependent block of the slowly activating delayed rectifier K+ current by chromanol 293B in guinea-pig ventricular cells
Time-dependent block of the slowly activating delayed rectifier K+ current by chromanol 293B in guinea-pig ventricular cells
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DOI：
10.1038/sj.bjp.0703126
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发表时间：
2000-03-01
影响因子：
7.3
通讯作者：
Iijima, T
中科院分区：
文献类型：
--
作者：
Fujisawa, S;Ono, K;Iijima, T
1在豚鼠心室肌细胞上记录到缓慢激活的延迟整流钾电流（I-Ks），并研究了色原烷醇衍生物293 B阻断I-Ks的机制。2在1-100 μ M 293 B存在下，I-Ks的激活相之后，在10 s去极化脉冲期间衰减较慢。衰减的速率和程度都以浓度依赖性方式增加。3 293 B浓度和块之间的关系显示希尔系数约为1。半抑制浓度约为3.0 μ M，在+20至+80 mV的各种膜电位下没有显著差异。4基于I-Ks通道的多个闭合和开放状态构建了293 B阻断的数学模型，并通过将模型拟合到原始电流迹线来计算阻断率。阻断速率常数与293 B浓度呈线性关系，表明结合化学计量比为1：1。在+80 mV时，阻断率为4 × 10（4）M-1 s（-1），解除阻断率为0.2 s（-1）。结果表明，293 B是一种开放通道阻断剂，其阻断率比迄今报道的各种离子通道的时间依赖性阻断率相对较小。
1 The slowly activating delayed rectifier K+ current (I-Ks) was recorded in single myocytes dissociated from guinea-pig ventricles and the mechanism underlying the block of I-Ks by a chromanol derivative, 293B, was investigated.2 In the presence of 1-100 mu M 293B, activation phase of I-Ks was followed by a slower decay during 10 s depolarizing pulses. Both the rate and extent of the decay were increased in a concentration-dependent manner.3 The relationship between the concentration of 293B and the block showed a Hill's coefficient of approximately 1. The half-inhibitory concentration was approximately 3.0 mu M and did not differ significantly at various membrane potentials from +20 to +80 mV.4 A mathematical model for the 293B block was constructed on the basis of multiple closed and open states for the I-Ks channels, and the blocking rate was calculated by fitting the model to the original current traces. The blocking rate constant showed a linear function with the 293B concentration, indicating 1 : 1 binding stoichiometry. At +80 mV the blocking rate was 4 x 10(4) M-1 s(-1) and the unblocking rate was 0.2 s(-1).5 The results indicate that 293B is an open channel blocker with relatively smaller blocking rate than those reported so far for time-dependent blockade of various ionic channels.