Effect of Cisapride on ATP-sensitive K Channel of Ventricular Cell

ABSTRACT

BACKGROUND: It has been generally accepted that Cisapride (Prepulsid?or propulsid?), a widely used gastrointestinal prokinetic agent, is associated with Torsades de Points, a life-threatening arrhythmia. Recently, cisapride-induced APD (action potential duration)-prolongation was inhibited by glibenclamide, a KATP channel blocker. But the direct effect of cisapride on K(ATP) channels has not been studied until now. Therefore, we investigated cisapride's effects on KATP channels of isolated rat ventricular myocytes. METHODS: After the isolation of rat ventricular myocytes, we analysed the single channel current with patch pipettes. The method of analysis was the student t-test. RESULTS: 1) Cisapride (10(-6) M- 10(-4) M) inhibited KATP channel opening without changing channel conductance Ki was about 20micronM, and Hill coefficient was 0.75. 2) Cisapride inhibited pinacidil-induced KATP channel opening in the cell attached mode. CONCLUSIONS: These results suggest that cisapride-induced APD prolongation and arrythmic effects may be partly related to KATP channel inhibition.