Beneficial effects of the dual L- and T-type Ca2+ channel blocker efonidipine on cardiomyopathic hamsters

Background: The T-type Ca2+ channel (TCC) is activated, and abnormalities of the TCC may be related to the pathogenesis of Ca2+ overload, in cardiomyopathic hamster hearts. The aims of the present study were to investigate the alteration in expression of the TCC and to examine the effects of a dual L-and T-type Ca2+ channel blocker, efonidipine (EFO), on cardiac function and TCC during development of heart failure in UM-X7.1 cardiomyopathic hamsters.

Methods and results: UM-X7.1 and golden hamsters were examined, and EFO was administered at the age of 20 weeks for 4 weeks. Cardiac function was examined, the expression of TCCalpha1G was measured, and ventricular myocytes were subjected to a patch-clamp study. At 24 weeks, vehicle-treated UM-X7.1 hamsters exhibited significant increases in left ventricular (LV) size, with marked decreases in ejection fraction (LVEF) compared with golden hamsters. In the UM-X7.1 group, the expression of TCCalpha1G increased during development of heart failure compared with the golden hamster group. In the UM-X7.1 group, EFO treatment significantly attenuated the decrease of LVEF without affecting blood pressure compared with the vehicle group. EFO treatment decreased heart rate (by approximately 10%) in both groups. In the golden hamster group, EFO treatment did not affect LV function. The TCC current in ventricular myocytes was significantly increased in UM-X7.1, and was inhibited by EFO in a dose-dependent manner.

Conclusions: In cardiomyopathic hamster hearts, abnormalities in the TCC may be at least in part related to the pathogenesis of abnormal Ca2+ homeostasis, and TCC-blocker treatment may decrease the TCC current, resulting in an improvement of cardiac function. TCC blocker therapy might be a new strategy for certain types of heart failure.