Effect of the calcium antagonists bepridil (CERM-1978) and verapamil on Ca++-dependent slow action potentials in frog skeletal muscle

Abstract

The calcium slow channels found in cardiac and smooth muscle are blocked by calcium-antagonistic agents. In the present study, the effects of the Ca++-antagonistic drugs bepridil and verapamil on the slow action potentials (APs) found in the frog skeletal muscle were examined. Slow APs were induced in Cl-- free (acetate substituted), Na+-free (sucrose substituted), high K+ (25 mM)media. A conventional two-microelectrode recording technique was used. Amplitude of the slow APs increases linearly with log [Ca]o with a slope of 28.2 mV/decade, suggesting that Ca++ is the major inward current carrier because this value approaches the theoretical slope of 29 mV/decade (at 21 degrees C) predicted by the Nernst equation for a divalent cation. Duration also increases with increases in [Ca]o. The slow APs were abolished by glycerol shock treatment, which disconnects the T-tubules from the surface membrane, suggesting that the slow APs originate in the T-tubules. Verapamil and bepridil depress the amplitude of the slow APs in a use-dependent manner at concentrations of 5 X 10-9 to 1 X 10-6 M and abolish the slow APs at 5 X 10-6 M. These drugs also decrease the rates of rise of the slow APs. Bepridil decreases the duration of the slow APs, whereas verapamil has little effect, suggesting that bepridil, in addition to blocking the slow channels, might also increase gk. Thus, the slow channels found in the T-tubular system of frog skeletal muscle have some of the same properties of slow channels in vascular smooth muscle and cardiac muscle.