Open channel block of HERG K+ channels by vesnarinone
Open channel block of HERG K+ channels by vesnarinone
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DOI：
10.1124/mol.60.2.244
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发表时间：
2001-08-01
影响因子：
3.6
通讯作者：
Sanguinetti, MC
中科院分区：
文献类型：
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作者：
Kamiya, K;Mitcheson, JS;Sanguinetti, MC
Vesnarinone是一种强心剂，阻断I-Kr，与其他I-Kr阻断剂不同，它产生频率依赖性的动作电位时程（APD）延长。为了阐明机制，我们研究了维司力农对HERG的影响，HERG是克隆的人I-Kr通道，在非洲爪蟾卵母细胞中异源表达。Vesnarinone引起HERG电流的浓度依赖性抑制，在0 mV时IC 50值为17.7 +/- 2.5 μ M（n = 6）。当HERG与β-亚基MiRP 1共表达时，测得类似的阻断效力（IC 50：15.0 ± 3.0 μ M，0 mV，n = 5）。HERG通道电流的紧张性阻滞是最小的（
Vesnarinone, a cardiotonic agent, blocks I-Kr and, unlike other I-Kr blockers, produces a frequency-dependent prolongation of action potential duration (APD). To elucidate the mechanisms, we studied the effects of vesnarinone on HERG, the cloned human I-Kr channel, heterologously expressed in Xenopus laevis oocytes. Vesnarinone caused a concentration-dependent inhibition of HERG currents with an IC50 value of 17.7 +/- 2.5 muM at 0 mV (n = 6). When HERG was coexpressed with the beta -subunit MiRP1, a similar potency for block was measured (IC50: 15.0 +/'- 3.0 muM at 0 mV, n = 5). Tonic block of the HERG channel current was minimal (