EFFECTS OF THE CALCIUM-ANTAGONISTS BEPRIDIL (CERM-1978) AND VERAPAMIL ON CA++-DEPENDENT SLOW ACTION-POTENTIALS IN FROG SKELETAL-MUSCLE

Abstract

The Ca slow channels found in cardiac and smooth muscle are blocked by Ca-antagonistic agents. The effects of the Ca2+-antagonistic drugs bepridil and verapamil on the slow action potentials (AP) found in frog skeletal muscle were examined. Slow AP were induced in Cl-free (acetate substituted), Na+-free (sucrose substituted), high K+ (25 mM) media. A conventional 2-microelectrode recording technique was used. Amplitude of the slow AP increases linearly with log [Ca]0 with a slope of 28.2 mV/decade, suggesting that Ca2+ is the major inward current carrier because this value approaches the theoretical slope of 29 mV/decade (at 21.degree. C) predicted by the Nernst equation for a divalent cation. Duration also increases with increases in [Ca]0. The slow AP were abolished by glycerol shock treatment, which disconnects the T-tubules from the surface membrane, suggesting that the slow AP originate in the T-tubules. Verapamil and bepridil depress the amplitude of the slow AP in a use-dependent manner at concentrations of 5 .times. 10-9 to 1 .times. 10-6 M and abolish the slow AP at 5 .times. 10-6 M. These drugs decrease the rates of rise of the slow AP. Bepridil decreases the duration of the slow AP, whereas verapamil has little effect, suggesting that bepridil, in addition to blocking the slow channels, might also increase gK. 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.