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

Some drugs acting on 5-hydroxytryptamine receptors inhibit the rapid compon ent of delayed rectifying potassium currents (I-Kr) in cardiac muscle cells . This is associated with lengthening of the QT interval in the cardiac cyc le and can lead to fatal arrhythmias. We investigated whether alosetron, a novel 5HT(3) 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 sele ctive I-Kr antagonist E4031. Cisapride (10(-6) M) inhibited the E4031-sensi tive 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 alosetro n for treatment of IBS should not be confounded by long QT syndrome. (C) 20 01 Elsevier Science Inc. All rights reserved.