N-n-Butyl haloperidol iodide inhibits the augmented Na+/Ca2+ exchanger currents and L-type Ca2+ current induced by hypoxia/reoxygenation or H2O2 in cardiomyocytes

Abstract N -n-butyl haloperidol iodide (F 2 ), a novel quaternary ammonium salt derivative of haloperidol, was reported to antagonize myocardial ischemia/reperfusion injuries. To investigate its mechanisms, we characterized the effects of F 2 on Na + /Ca 2+ exchanger currents ( I NCX ) and the L-type Ca 2+ channel current ( I Ca,L ) of cardiomyocytes during either hypoxia/reoxygenation or exposure to H 2 O 2 . Using whole-cell patch-clamp techniques, the I NCX and I Ca,L were recorded from isolated rat ventricular myocytes. Exposure of cardiomyocytes to hypoxia/reoxygenation or H 2 O 2 enhanced the amplitude of the inward and outward of I NCX and I Ca,L . F 2 especially inhibited the outward current of Na + /Ca 2+ exchanger, as well as the I Ca,L , in a concentration-dependent manner. F 2 inhibits cardiomyocyte I NCX and I Ca,L after exposure to hypoxia/reoxygenation or H 2 O 2 to antagonize myocardial ischemia/reperfusion injury by inhibiting Ca 2+ overload.