Reversible Inhibition of Potassium Contractures by optical isomers of verapamil and D 600 on slow muscle fibres of the frog.
Potassium-induced contractures were measured isometrically in slow fibres of gastrocnemius muscle from the frog Leptodactylus ocellatus. Optical isomers of verapamil and of D 600 decreased the tension of K-contractures with the following characteristics: 1. 90 min exposures of the muscles to the (-)isomers of the drugs were more effective in decreasing tension of 40 mM KCl-contractures when successive challenges to 40 mM KCl were made each 10-15 min than without challenges during the incubation time. 2. In contrast to the depressing effect of (-)isomers of verapamil and D 600, the decrease of K-contractures by 1 mM EGTA in "Ca-free" solutions was independent on the history of 40 mM KCl-contractures. 3. The threshold concentration of K to cause contractures was the lower the lower the Ca-concentration. This relationship was little affected by (-)verapamil at concentrations of the drug which depressed by 50% the tension of 40 mM KCl-contractures in 1.8 mM CaCl2. 4. Verapamil and its methoxy-derivative D 600 were equipotent in depressing 40 mM KCl-contractures. Their optical (-)isomers were 4 to 5 times more potent than their corresponding (+)isomers. 5. K-tension curves in the presence of 6.1 muM (-)verapamil in 1.8 mM CaCl2 were similar to curves in 0.18 mM CaCl2 without the drug. 6. K-tension curves in 10 mM CaCl2 were shifted by (-)verapamil in nearly parallel manner towards higher K-concentrations. 7. The stereoselective decrease of K-contractures by verapamil and D 600 may be due to blockade of inward Ca-flux and to retardation of the reavailability  of Ca2+ for release during partial depolarizations with K.
D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D005711:Gallopamil / Q000494:pharmacology*; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects*; D009132:Muscles / Q000187:drug effects; D011188:Potassium / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D013237:Stereoisomerism; D013997:Time Factors; D014700:Verapamil / Q000031:analogs & derivatives* / Q000494:pharmacology*
D005711:Gallopamil; D004533:Egtazic Acid; D014700:Verapamil; D011188:Potassium; D002118:Calcium