Positive Inotropic and Positive Lusitropic Effects of Dofetilide on Isolated Rat Ventricular Cells by Enhancing Na + /Ca 2+ Exchange

Abstract

This study aimed to investigate the positive inotropic effect of dofetilide on rat ventricular myocytes and the mechanism underlying it. Whole-cell patch clamp experiment results showed that dofetilide increased INa/Ca in a concentration-dependent manner from 0.03 to 1.0mol/L on both inward and outward transport directions in isolated rat ventricular cells. Single cell ionic image experiments results showed that when stimulated by field-stimulation, 0.2mol/L dofetilide significantly enhanced Ca2+ transient and cell shortening in rat ventricular myocytes. It also increased the calcium sensitivity, shortened the Ca2+ transient duration and myocyte diastolic duration. When connected the patch clamp system to the ionic imaging system, 0.2mol/L dofetilide (with the presence of 1mol/L nicardipine) had no active effect on ICa, but increased Ca2+ transient and cell shortening. 0.6mol/L KB-R7943 depressed the effects of dofetilide on Ca2+ transient and cell shortening without any influence on ICa. Our results demonstrated that Dofetilide had positive inotropic effect and positive lusitropic effect on rat ventricular myocytes. The enhancement of Na+/Ca2+ exchange might be involved in these effects.