Paralysis of frog skeletal muscle fibres by the calcium antagonist D-600

Abstract

The Ca2+ channel blocker D-600 (methoxyverapamil) paralyses single muscle fibres of the frog: fibres exposed to the drug at 7 degrees C give a single K+ contracture after which they are paralysed, unable to contract in response to electrical stimulation or further applications of K+. Paralysed fibres contract in response to caffeine and have normal resting potentials and action potentials. Fibres treated with D-600 at 22 degrees C are not paralysed. Paralysed fibres warmed to 22 degrees C recover contractile properties: they twitch and give K+ contractures. Other workers have shown that D-600 blocks a Ca2+ channel at room temperature; thus, the paralytic action of D-600 is probably mediated by a different membrane protein, perhaps a different Ca2+ channel from that blocked at room temperature. These results suggest that the binding of D-600 can disrupt the mechanism coupling electrical potential changes across the T membrane to Ca2+ release from the sarcoplasmic reticulum.