APPS November 2002 Meeting Abstract 1360


David R. Plant, Gordon S. Lynch, Muscle Mechanics Laboratory, Department of Physiology, The University of Melbourne, Victoria, 3010, Australia.

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 5 depolarizations (n = 14 fibres) vs. mdx, 18 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.

(1) Lamb GD, Stephenson DG. Journal of Physiology. 1990;423:495-517.

(2) Plant DR, Lynch GS. Journal of Physiology. 2002;543: in press.

Supported by the Muscular Dystrophy Association (USA).

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