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Alosetron and the rapid component of delayed rectifying potassium current in cardiac cells.

机译:阿洛司琼和心脏细胞中延迟整流钾电流的快速成分。

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Some drugs acting on 5-hydroxytryptamine receptors inhibit the rapid component of delayed rectifying potassium currents (I(Kr)) in cardiac muscle cells. This is associated with lengthening of the QT interval in the cardiac cycle and can lead to fatal arrhythmias. We investigated whether alosetron, a novel 5HT3 antagonist proposed for treatment of irritable bowel syndrome (IBS), blocks I(Kr) in guinea pig cardiac myocytes. I(Kr) was isolated under whole-cell voltage clamp, and was identified by its sensitivity to the selective I(Kr) antagonist E4031. Cisapride (10(-6) M) inhibited the E4031-sensitive current while alosetron (10(-10)-10(-6) M) had no effect on I(Kr). We also found that alosetron did not inhibit I(Ks). Therefore, use of alosetron for treatment of IBS should not be confounded by long QT syndrome.
机译:一些作用于5-羟色胺受体的药物会抑制心肌细胞中延迟整流钾电流(I(Kr))的快速成分。这与心动周期中QT间隔的延长有关,并可能导致致命的心律失常。我们调查了alosetron(一种提议用于治疗肠易激综合征(IBS)的新型5HT3拮抗剂)是否能阻断豚鼠心肌细胞中的I(Kr)。 I(Kr)在全细胞电压钳下分离,并通过其对选择性I(Kr)拮抗剂E4031的敏感性进行鉴定。西沙必利(10(-6)M)抑制E4031敏感电流,而阿洛司琼(10(-10)-10(-6)M)对I(Kr)没有影响。我们还发现alosetron不会抑制I(Ks)。因此,使用阿洛司琼治疗IBS不应与长期QT综合征混淆。

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