Effects of Cisapride on Action Potential Duration and on ATP-Sensitive K Channel in Guinea Pig Ventricular Muscles

ABSTRACT

PURPOSE: Cisapride(Prepulsid(R)) has been recently associated with long QT syndrome. It has been reported to cause Torsades de Pointes and induce early afterdepolarization in rabbit Purkinje fibers. We investigated the electrophysiological effects of cisapride on cardiac action potential duration and ATP-sensitive K channel in papillary muscles. METHODS: Cardiac action potentials in guinea pig papillary muscle were recorded with microelectrodes by electrical stimulation. The concentration and time dependent effects of cisapride on the ventricular muscle were studied. The effects of cisapride were evaluated in the presence of potassium channel blockers. The effect of cisapride in isolated single ventricular myocyte was also evaluated. RESULTS: Cisapride lengthened the action potential duration(APD). The lengthening depended on doses of cisapride and exposure time. The APD prolongation was attenuated by glibenclamide pretreatment, not tetraethylammonium. Cisapride inhibits pinacidil-induced KATP channel activity dose dependently in cell-attached membrane patch. APD prolongation in Purkinje fibers was more prominent than these in the ventricular muscle. CONCLUSION: These results suggest that cisapride lengthens APD in ventricular muscle and that cisapride-induced APD prolongation may be partially linked with KATP channel inhibition.