APPS November 2002 Meeting Abstract 1360


DEPOLARIZATION-INDUCED CONTRACTION AND SR FUNCTION IN MECHANICALLY SKINNED FAST MUSCLE FIBRES FROM DYSTROPHIC mdx MICE

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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