EFFECTS OF RYANODINE AND IODOACETAMIDE ON NORMAL AND DYSTROPHIC C57 BL MOUSE DIAPHRAGM MUSCLES

Abstract

The effects of ryanodine and iodoacetamide were examined on bundles isolated from diaphragm muscles of normal and dystrophic mice (C57 BL 6J strains). At 22°C, the addition of ryanodine or iodoacetamide for external concentrations higher than 10^-7 M and 5 × 10^-4 M respectively produced an irreversible increase in the resting tension after a period of 20-40 min. For both drugs the latent period was reduced if K-contractures were generated simultaneously. However, in the presence of ryanodine the phasic K-contracture was followed by a slow and transient increase in tension. The peak value of this second phase related to the amplitude of the 110 mM K-contracture was always smaller in dystrophic than in normal diaphragm muscle. Using lower concentrations, the effects of the two drugs were examined on the repriming of 110 mM [K]₀-contractures. Following application of iodoacetamide (5-10^-6 M to 10^-4 M) the recovery time was increased to the same extent in both types of muscle. By contrast, for a given amount of ryanodine, the rate of repriming was more affected in normal than in dystrophic muscles. It is proposed that ryanodine acts at a specific site of the terminal cisternae from the sarcoplasmic reticulum (SR) where dystrophy induces pathological modifications.