Effect of caffeine and high potassium on normal and dystrophic mouse EDL muscles at various developmental stages.

Abstract

EDL muscles from normal and dystrophic (dy2j) mice of various ages were examined. Muscles were divided into three groups according to age: 7 to 14 days postnatal, 16 to 21 days postnatal, and 6 months old, to assess age and/or phenotype related differences in the muscle response to caffeine or high K+. The response of normal muscles to caffeine decreased with age and reached adult characteristics between the second and third week of postnatal life. Their response to high K+ also changed during postnatal development; specifically, the time taken to recover to 50% pretest twitch tension decreased with age, probably reflecting developmental changes in Cl- conductance. Up to 21 days of age, the sensitivity of dystrophic muscles to both caffeine and high K+ was essentially similar to normal, while marked differences were observed in the adult. Taken altogether, our results suggest that while the maturation of a number of systems might be delayed in dystrophic muscles at preclinical stages of the disease, their e-c coupling and SR function (Ca2+ release and reuptake) appear to be quite normal. Our results further suggest that the "abnormal" responses of dystrophic muscles at more advanced stages of the disease, when challenged by drugs acting on either of these systems, may be explained in terms of changes in muscle fiber type proportions.