APPS November 2002 Meeting Abstract 1360

The mdx mouse has a dystrophin gene mutation and a lack of dystrophin expression in muscle tissues and has been used in a wide range of investigations probing the underlying mechanisms of Duchenne muscular dystrophy (DMD). Little is known about the effect of an absence of dystrophin on the functional characteristics of excitation-contraction (E-C) coupling in muscle fibres of mdx mice. The individual steps involved in E-C coupling and sarcoplasmic reticulum (SR) Ca²⁺ handling can be assessed using single mechanically skinned muscle fibres.¹ The purpose of this study was to characterise E-C coupling and SR function in mechanically skinned single muscle fibres from mdx mice. We tested the hypothesis that muscle fibres from mdx mice have abnormal E-C coupling and SR function. Fibres were prepared from the fast twitch extensor digitorum longus (EDL) muscles of adult control (C57BL/10 ScSn) and dystrophic (mdx) mice that were killed by rapid cervical dislocation. Fibres were tested according to the methods we have described previously.² Peak height of depolarization-induced contraction (DICR) was similar in EDL muscle fibres from mdx and control mice, indicating normal voltage regulation of Ca²⁺ release. Nevertheless, rundown of peak DICR (DICR < 50% of initial) was reached more rapidly in fibres from mdx than control mice [control, 32 ą 5 depolarizations (n = 14 fibres) vs. mdx, 18 ą 1 depolarizations (n = 7) before rundown, P < 0.05]. Normalized SR Ca²⁺ reloading was not different in fibres from control and mdx mice, nor was any difference observed in SR Ca²⁺ leak. Peak height of contraction over a range of caffeine concentrations (2 - 7 mM) was diminished in mdx compared to control mice (P < 0.05), indicating depressed SR Ca²⁺ release. Our findings indicate that although SR Ca²⁺ release is affected, E-C coupling is conserved in single fibres from mdx mice.