Paralysis of frog skeletal muscle fibres by the calcium antagonist D-600.
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.
D000200:Action Potentials; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005711:Gallopamil / Q000494:pharmacology*; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D009132:Muscles / Q000187:drug effects*; D011188:Potassium / Q000494:pharmacology; D011896:Rana temporaria; D013696:Temperature; D014700:Verapamil / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D005711:Gallopamil; D014700:Verapamil; D011188:Potassium