Abstract. In guinea pig ventricular cardiomyocytes, the R(-)-enantiomer of efonidipine concentration-dependently blocked T-type Ca 2+ current with 85% inhibition at 1 mM. In contrast, R(-)-efonidipine (1 mM) had no effect on the L-type Ca 2+ current and Ca 2+ transient in cardiomyocytes and contractile force in papillary muscles. Thus, R(-)-efonidipine is a highly selective blocker of the T-type Ca 2+ current in native myocardia.

Abstract. The contribution of the T-type Ca 2+ current to cardiac pacemaking was examined in isolated right atrial tissue from the mouse, guinea pig, and rabbit using a specific blocker, R(−)-efonidipine. At 10 −6 M, R(−)-efonidipine produced negative chronotropy, which was prominent in the mouse and small but significant in the guinea pig. No effect was observed in the rabbit. Microelectrode recordings revealed that R(−)-efonidipine significantly prolongs the pacemaker (phase 4) depolarization of the sinoatrial-node action potential in the mouse and guinea pig. These results provide the first pharmacological evidence that the contribution of T-type Ca 2+ current to cardiac pacemaking differs among experimental animal species.

No abstract

No abstract