Apamin, a highly specific Ca2+ blocking agent in heart muscle.

Apamin, a bee venom polypeptide, was recently reported to block specifically the Ca2+-dependent K+ channels that are not blocked by tetraethylammonium chloride in muscle cells. We report here that apamin blocked the naturally occurring slow action potentials (APs) in cultured cell reaggregates from chick hearts. The effects of apamin were not reversible on washout with Tyrode solution only (up to 24 h), but quinidine (10(-8) M) reversed the apamin blockade of the slow channels. Apamin also blocked the isoproterenol-induced slow APs in freshly isolated chick ventricular cells depolarized by 22 mM extracellular K+ concentration ([K+]o) in a dose-dependent fashion (10(-12) to 10(-10) M). Apamin at 5 X 10(-11) M blocked the isoproterenol-induced slow APs without affecting the membrane potential. Washout (with Tyrode solution containing 22 mM [K+]o and 10(-6) M isoproterenol) did not recover the slow APs. However, recovery of the slow APs was possible only when quinidine (10(-8) M) was added to the superfusion medium. The fast APs were rapidly restored by washout with Tyrode solution only. The present data show that apamin is a highly specific compound that tightly binds to the Ca2+ slow channels, thus blocking the slow APs in heart muscle. In addition, quinidine antagonizes the apamin binding on the slow APs.