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The action potential‐evoked sarcoplasmic reticulum calcium release is impaired in mdx mouse muscle fibres
Author(s) -
Woods Christopher E.,
Novo David,
DiFranco Marino,
Vergara Julio L.
Publication year - 2004
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2004.061291
Subject(s) - egta , mdx mouse , endoplasmic reticulum , duchenne muscular dystrophy , chemistry , skeletal muscle , calcium , medicine , biophysics , endocrinology , muscle contraction , extensor digitorum longus muscle , membrane potential , anatomy , biology , biochemistry , dystrophin
The mdx mouse, a model of the human disease Duchenne muscular dystrophy, has skeletal muscle fibres which display incompletely understood impaired contractile function. We explored the possibility that action potential‐evoked Ca 2+ release is altered in mdx fibres. Action potential‐evoked Ca 2+ ‐dependent fluorescence transients were recorded, using both low and high affinity Ca 2+ indicators, from enzymatically isolated fibres obtained from extensor digitorum longus (EDL) and flexor digitorum brevis (FDB) muscles of normal and mdx mice. Fibres were immobilized using either intracellular EGTA or N ‐benzyl‐ p ‐toluene sulphonamide, an inhibitor of the myosin II ATPase. We found that the amplitude of the action potential‐evoked Ca 2+ transients was significantly decreased in mdx mice with no measured difference in that of the surface action potential. In addition, Ca 2+ transients recorded from mdx fibres in the absence of EGTA also displayed a marked prolongation of the slow decay phase. Model simulations of the action potential‐evoked transients in the presence of high EGTA concentrations suggest that the reduction in the evoked sarcoplasmic reticulum Ca 2+ release flux is responsible for the decrease in the peak of the Ca 2+ transient in mdx fibres. Since the myoplasmic Ca 2+ concentration is a critical regulator of muscle contraction, these results may help to explain the weakness observed in skeletal muscle fibres from mdx mice and, possibly, Duchenne muscular dystrophy patients.