Inhibition of Ca2+ inward current in rabbit sinoatrial node by bunazosin, an alpha-adrenoceptor antagonist.
The electrophysiological effects of bunazosin, a novel alpha-adrenoceptor antagonist, were examined on isolated spontaneously beating sinoatrial node preparations of the rabbit by means of a double-microelectrode voltage clamp method. Bunazosin (above 10 microM) reduced the beating frequency, and the maximum rate of rise and the amplitude of action potentials. The slope of the diastolic depolarization (phase 4) was also decreased by the drug whereas the action potential duration at 50% repolarization was prolonged. Bunazosin decreased the slow inward current (Isi) and the time-dependent potassium outward current (IK). However, the major effect was the reduction of Isi. The results indicate that bunazosin, an alpha-adrenoceptor antagonist, depresses the action potential and automaticity of the sinoatrial node by inhibition of Ca channels.
D000200:Action Potentials / Q000187:drug effects; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D002121:Calcium Channel Blockers; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D011799:Quinazolines / Q000494:pharmacology*; D011817:Rabbits; D012849:Sinoatrial Node / Q000187:drug effects / Q000378:metabolism*
D000317:Adrenergic alpha-Antagonists; D002121:Calcium Channel Blockers; D007473:Ion Channels; D011799:Quinazolines; C018176:bunazosin