Summary
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:
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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.
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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.
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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.
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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.
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5.
K-tension curves in the presence of 6.1 μM (-)verapamil in 1.8 mM CaCl2 were similar to curves in 0.18 mM CaCl2 without the drug.
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6.
K-tension curves in 10 mM CaCl2 were shifted by (-)verapamil in nearly parallel manner towards higher K-concentrations.
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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.
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Kaumann, A.J., Uchitel, O.D. Reversible inhibition of potassium contractures by optical isomers of verapamil and D 600 on slow muscle fibres of the frog. Naunyn-Schmiedeberg's Arch. Pharmacol. 292, 21–27 (1976). https://doi.org/10.1007/BF00506485
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DOI: https://doi.org/10.1007/BF00506485