Inhibitory Mechanism of Carvedilol on L-type Ca^2＋ Current in Rat Ventricular Myocytes

Objectives The effects of carvedilol on calcium current (ICa) were investigated in isolated adult rat ventricular myocytes. Methods ICa was recorded by using whole-cell patch-clamp recording technique. Results Carvedilol reversibly inhibited ICa in a concentration-dependent manner, carvedilol at 0.1,0.3, 1 and 10μmol/L in the extracellular solution decreased peak ICa by 1.52%, 18.04%, 37.34% and 72.18%,respectively. The steady-state inactivation curve of ICa was shifted to more negative potentials, while the activation curve was not altered. The recovery from inactivation was shifted to right direction, it could not be recovered completely. In addition, Pretreatment of ventricular myocytes with prazosin and propranolol couldn't block the carvedilol-induced reduction of ICa.Conclusions Carvedilol inhibits ICa in adult rat ventricular myocytes by mechanisms involving preferential interaction with the inactivated state of calcium channel.