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 (ICa) was studied in single ventricular myocytes of the guinea-pig using a whole-cell patch-clamp technique. 2. Bunazosin (10-100 microM) decreased ICa in a concentration-dependent manner with an IC50 of 60 microM during depolarization to + 10 mV from the holding potential of -40 mV. 3. As for the inactivation process of ICa, 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 microM and 70 microM bunazosin. 4. Inhibition of ICa by the compound (10 microM) 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.
Kotake
H
H
First Department of Internal Medicine, Tottori University, Yonago, Japan.
Noguchi
N
N
Matsuoka
S
S
Hisatome
I
I
Hasegawa
J
J
Mashiba
H
H
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D006352:Heart Ventricles / Q000187:drug effects; D011799:Quinazolines / Q000494:pharmacology*
D000317:Adrenergic alpha-Antagonists; D002121:Calcium Channel Blockers; D011799:Quinazolines; C018176:bunazosin