Blocking action of chromanol 293B on the slow component of delayed rectifier K+ current in guinea‐pig sino‐atrial node cells
Blocking action of chromanol 293B on the slow component of delayed rectifier K+ current in guinea‐pig sino‐atrial node cells
复制标题
色醇293B对豚鼠窦房结细胞延迟整流K+电流慢分量的阻断作用
DOI：
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发表时间：
2002
影响因子：
7.3
通讯作者：
H. Matsuura
中科院分区：
文献类型：
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作者：
W. Ding;F. Toyoda;H. Matsuura
在豚鼠心房（SA）结细胞中，延迟整流K+电流（IK）由IK的快速和缓慢激活成分（分别为IKr和IKs）组成。本研究采用全细胞膜片钳技术对豚鼠SA结细胞中的IKs进行了阻断作用。293B在L型Ca2+电流（ICa，L）和IKr被抑制的条件下，通过保持电位为- 50 mV的4秒去极化电压脉冲激发阻滞IKs；该效应与浓度有关，IC50为5.3 μM，当4 s去极化电压步进到+50 mV时，IKs尾电流的振幅下降。在去极化电压过程中，IKs的293B阻滞随着时间的推移而进展，且浓度越高阻滞越快。在洗去药物后几分钟内，即使在高药物浓度（50 μM）下达到最大效果（几乎完全阻断），293B对ik的阻滞也会完全逆转。β -肾上腺素能激动剂异丙肾上腺素（1 μM）对IKs的最大刺激作用在50 μM时，293B对IKs的阻滞程度略低于未刺激IKs（94.0±0.98%阻滞，n=6 vs 99.4±0.45%阻滞，n=6， P<0.01）。我们得出结论，在豚鼠窦房结细胞中(1)293B在β -肾上腺素能刺激中是一种有效的、完全可逆的IKs阻滞剂，(2)293B在去极化电压步骤中以时间依赖性的方式发生阻断。
In guinea‐pig sino‐atrial (SA) node cells the delayed rectifier K+ current (IK) is composed of rapidly and slowly activating components of IK (IKr and IKs, respectively). The present study was undertaken to characterize the blocking action of the chromanol derivative 293B on IKs in guinea‐pig SA node cells using whole‐cell patch‐clamp technique. Bath application of 293B blocked IKs, elicited by 4‐s depolarizing voltage pulses from a holding potential of −50 mV, under conditions in which the L‐type Ca2+ current (ICa,L) and IKr were inhibited; the effect was concentration‐dependent with an IC50 of 5.3 μM, when evaluated by the decrease in the amplitude of IKs tail current following 4‐s depolarizing voltage steps to +50 mV. The 293B block of IKs progressed with time during depolarizing voltage steps with a more rapid block at higher concentrations. The block of IKs by 293B was fully reversed within a few minutes after washing off the drug, even when a maximal effect (a nearly full block) was achieved at high drug concentration (50 μM). Bath application of 293B at 50 μM greatly and reversibly reduced the amplitude of IKs which is maximally stimulated by β‐adrenergic agonist isoprenaline (1 μM), while the degree of 293B block of the isoprenaline‐stimulated IKs was slightly but significantly smaller than that of non‐stimulated IKs (94.0±0.98% block, n=6 vs 99.4±0.45% block, n=6; P<0.01). We conclude that, in guinea‐pig SA node cells (i) 293B is a potent and fully reversible blocker of IKs in control and during β‐adrenergic stimulation and (ii) block with 293B occurs in a time‐dependent manner during depolarizing voltage steps.
影响因子：
37.8
作者：
Shimizu, W;Antzelevitch, C
通讯作者：
Antzelevitch, C
影响因子：
20.1
作者：
LIU, DW;ANTZELEVITCH, C
通讯作者：
ANTZELEVITCH, C