The action potential-evoked sarcoplasmic reticulum calcium release is impaired in mdx mouse muscle fibres.
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.
Woods
Christopher E
CE
Department of Physiology, UCLA School of Medicine, Los Angeles, CA 90095, USA.
Novo
David
D
DiFranco
Marino
M
Vergara
Julio L
JL
D000200:Action Potentials / Q000502:physiology; D000465:Algorithms; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002614:Chelating Agents / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D004594:Electrophysiology; D005456:Fluorescent Dyes; D051379:Mice; D018101:Mice, Inbred mdx; D018485:Muscle Fibers, Skeletal / Q000378:metabolism*; D020388:Muscular Dystrophy, Duchenne; D012519:Sarcoplasmic Reticulum / Q000378:metabolism*
D002614:Chelating Agents; D005456:Fluorescent Dyes; D004533:Egtazic Acid; D002118:Calcium