Contraction-induced injury to single permeabilized muscle fibers from mdx, transgenic mdx, and control mice

Abstract

Muscle fibers of mdx mice that lack dystrophin are more susceptible to contraction-induced injury, particularly when stretched. In contrast, transgenic mdx (tg -mdx) mice, which overexpress dystrophin, show no morphological or functional signs of dystrophy. Permeabilization disrupts the sarcolemma of fibers from muscles of mdx, tg- mdx, and control mice. We tested the null hypothesis stating that, after single stretches of maximally activated single permeabilized fibers, force deficits do not differ among fibers from extensor digitorum longus muscles of mdx, tg -mdx, or control mice. Fibers were maximally activated by Ca²⁺ (pCa 4.5) and then stretched through strains of 10%, 20%, or 30% of fiber length ( L _f) at a velocity of 0.5 L _f/s. Immediately after each strain, the force deficits were not different for fibers from each of the three groups of mice. When collated with studies of membrane-intact fibers in whole muscles of mdx, tg -mdx, and control mice, these results indicate that dystrophic symptoms do not arise from factors within myofibrils but, rather, from disruption of the sarcolemmal integrity that normally provides protection from contraction-induced injury.