Concentration-dependent block of sodium current in guinea pig ventricular myocytes by a class III antiarrhythmic agent, MS-551.
Concentration-dependent block of sodium current in guinea pig ventricular myocytes by a class III antiarrhythmic agent, MS-551.
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III 类抗心律失常药 MS-551 对豚鼠心室肌细胞中钠电流的浓度依赖性阻断。
DOI：
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发表时间：
1998
影响因子：
3
通讯作者：
Masami Yamanaka
中科院分区：
文献类型：
--
作者：
Kazuyuki Suzuki;T. Furukawa;Yutaka Koyama;T. Sagawa;M. Nishimura;Masami Yamanaka
尽管MS-551被归类为III类抗心律失常药（K+通道阻滞剂），但其对Na+通道的影响尚未完全表征。我们研究了MS-551对豚鼠心室肌细胞Na+电流（I（Na））的影响。MS-551在-140 mV的保持电位下以浓度依赖性方式阻断I（Na）。浓度-反应曲线显示，阻断静息通道的中位抑制浓度（IC 50）为292 +/- 20 μ M，希尔系数为1（n = 11）。虽然MS-551，300 μ M，没有表现出使用依赖性阻滞，但它使稳态失活曲线向超极化方向移动了6.3 +/- 0.8 mV，并延迟了从长去极化的恢复过程。这种延迟被认为与药物解结合有关，并由三重指数函数表示。最慢分量的时间常数为409 +/- 35 ms，该分量的振幅占总电流振幅的比例为14 +/- 3%（n = 6）。因此，估计失活的Na+通道的IC 50最大为169 μ M。这些结果表明，MS-551对静息和失活Na+通道均具有低亲和力。
Although MS-551 is classified as a class III antiarrhythmic agent (K+ channel blocker), its effect on the Na+ channel has not been fully characterized. We investigated the effect of MS-551 on the Na+ current (I(Na)) in isolated guinea pig ventricular myocytes. MS-551 blocked I(Na) in a concentration-dependent manner at a holding potential of -140 mV. The concentration-response curve revealed that the median inhibitory concentration (IC50) for the block of resting channel was 292 +/- 20 microM with a Hill coefficient of 1 (n = 11). Although MS-551, 300 microM, did not show a use-dependent block, it shifted the steady-state inactivation curve in a hyperpolarizing direction by 6.3 +/- 0.8 mV and delayed the recovery process from long depolarization. This delay was considered to be related to the drug unbinding and was expressed by a triple exponential function. The slowest component had a time constant of 409 +/- 35 ms, and the proportion of the amplitude of this component to the total current amplitude was 14 +/- 3% (n = 6). The IC50 for the inactivated Na+ channel was thus estimated to be 169 microM at maximum. These results suggest that MS-551 has a low affinity for both the resting and inactivated Na+ channel.
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影响因子：
3.6
作者：
C. Starmer;A. Grant
通讯作者：
C. Starmer;A. Grant
利多卡因对大鼠单心室细胞钠电流的电压和使用依赖性影响。
影响因子：
20.1
作者：
Sanchez-Chapula,J;Tsuda,Y;Josephson,IR
通讯作者：
Josephson,IR
氯丙嗪阻断单个豚鼠心肌细胞钠通道的动力学。
DOI：
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发表时间：
1989
期刊：
The Journal of pharmacology and experimental therapeutics
影响因子：
--
作者：
Ogata,N;Nishimura,M;Narahashi,T
通讯作者：
Narahashi,T
利多卡因阻断单个人心房细胞钠通道的特征。
DOI：
--
发表时间：
1993
期刊：
The Journal of pharmacology and experimental therapeutics
影响因子：
--
作者：
Jia,H;Furukawa,T;Singer,DH;Sakakibara,Y;Eager,S;Backer,C;Arentzen,C;Wasserstrom,JA
通讯作者：
Wasserstrom,JA
室性快速心律失常患者七种抗心律失常药物的比较。
DOI：
10.1056/nejm199308123290702
发表时间：
1993
期刊：
The New England journal of medicine
影响因子：
--
作者：
Mason,JW
通讯作者：
Mason,JW