BUNAZOSIN, AN ALPHA-ADRENOCEPTOR ANTAGONIST, BLOCKS CALCIUM CURRENT IN GUINEA-PIG VENTRICULAR MYOCYTES

1. Effect of bunazosin, an alpha-1-adrenoceptor antagonist, upon the slow inward Ca2+ current (I(Ca)) was studied in single ventricular myocytes of the guinea-pig using a whole-cell patch-clamp technique. 2. Bunazosin (10-100-mu-M) decreased I(Ca) in a concentration-dependent manner with an IC50 of 60-mu-M during depolarization to +10 mV from the holding potential of -40 mV. 3. As for the inactivation process of I(Ca), the steady-state inactivation (f infinity) curve was shifted toward more negative potentials from -12 mV to -17 mV and -21 mV at f infinity = 0.5, by 30-mu-M and 70-mu-M bunazosin. 4. Inhibition of I(Ca) by the compound (10-mu-M) was also dependent on stimulation frequency, with greater block induced at 2 Hz (50%) than at 0.33 Hz (13%). 5. It is concluded that bunazosin possesses a direct Ca2+ channel-blocking (class 4) action in a rate-dependent fashion.