Effects of Dexmedetomidine on L-Type Calcium Current in Rat Ventricular Myocytes.

BACKGROUND Dexmedetomidine is a highly selective α2-adrenoreceptor agonist with sedative, analgesic and sympatholytic properties. Its cardiac protective effect cannot be ignored, notwithstanding its associated adverse drug reactions. This study aimed to investigate the effects of dexmedetomidine on L-type calcium current (ICa-L) in adult rat ventricular myocytes, and to clarify the electrophysiological mechanism of its effect on cardiomyocytes. METHODS Single rat ventricular myocytes were obtained by enzymatic dissociation method. Myocytes were perfused with external solutions containing various concentrations of dexmedetomidine at a flow rate of 2-3 ml/min for 5 min. Whole-cell current recordings were performed using the conventional whole-cell patch-clamp technique. Besides, the effects of 1 μM yohimbine, an alpha-2 adrenergic antagonist, were given alone or in combination with 10 ng/ml dexmedetomidine. RESULTS Dexmedetomidine inhibited the amplitude of ICa-L in a concentration-dependent manner. The current voltage curve was shifted upwards. The steady activated curves were shifted to the right and the V1/2 activation of the ICa-L were increased by dexmedetomidine at the high concentration (10 and 200 ng/ml). Dexmedetomidine did not affect the ICa-L steady-state inactivation curve, but shifted down the recovery curve. Yohimbine did not have influence on ICa-L. However, inhibition of ICa-L by dexmedetomidine at the concentration of 10 ng/ml was partially reversed by yohimbine. CONCLUSIONS Dexmedetomidine can attenuate ICa-L in adult rat ventricular myocytes, which may contribute to its negative effects on myocardia contractility and cardiac electrophysiology. Its inhibitory effect on ICa-L is partially associated with alpha-2 adrenergic receptors. KEY WORDS Cardiology; Dexmedetomidine; L-type calcium current; Ventricular myocytes; Whole-cell patch clamp.