IMR Press / JMCM / Volume 4 / Issue 2 / DOI: 10.31083/j.jmcm0402005
Open Access Review
Role of molecular and metabolic defects in impaired performance of dystrophic skeletal muscles
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1 Institute of Cardiovascular Sciences, St. Boniface Hospital Albrechtsen Research Centre and Department of Physiology and Pathophysiology, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB R2H 2A6, Canada
2 School of Medicine, Jordan University of Science and Technology, Irbid, 3030 Ar-Ramtha, Jordan
3 Department of Kinesiology, Nutrition and Food Science, California State University, Los Angeles, CA 90802, USA
*Correspondence: (Naranjan S. Dhalla)
J. Mol. Clin. Med. 2021, 4(2), 47–67;
Submitted: 4 November 2020 | Revised: 8 May 2021 | Accepted: 26 May 2021 | Published: 20 June 2021
Copyright: © 2021 The Author(s). Published by IMR Press.
This is an open access article under the CC BY 4.0 license (

There occurs a progressive weakness and wastage of skeletal muscle in different types of muscular dystrophy. The loss of muscle fibers in dystrophic muscle with impaired function is associated with leakage of intracellular enzymes, maldistribution of electrolyte content and metabolic defects in myocytes. Marked increases in the sarcolemma (SL) Na+-K+ ATPase and Ca2+/Mg2+-ecto ATPase activities, as well as depressions in the sarcoplasmic reticulum (SR) Ca2+-uptake and Ca2+-pump ATPase activities were seen in dystrophic muscles of a hamster model of myopathy. In addition, impaired mitochondrial oxidative phosphorylation and decrease in the high energy stores as a consequence of mitochondrial Ca2+-overload were observed in these myopathic hamsters. In some forms of muscular dystrophy, it has been shown that deficiency of dystrophin produces marked alterations in the SL permeability and promotes the occurrence of intracellular Ca2+-overload for inducing metabolic defects, activation of proteases and contractile abnormalities in dystrophic muscle. Increases in SR Ca2+-release channels, SL Na+-Ca2+ exchanger and SL store-operated Ca2+-channels have been reported to induce Ca2+-handling abnormalities in a mouse model of muscular dystrophy. Furthermore, alterations in lipid metabolism and development of oxidative stress have been suggested as mechanisms for subcellular remodeling and cellular damage in dystrophic muscle. Although, several therapeutic interventions including gene therapy are available, these treatments neither fully prevent the course of development of muscular disorder nor fully improve the function of dystrophic muscle. Thus, extensive reasearch work with some novel inhibitors of oxidative stress, SL Ca2+-entry systems such as store-operated Ca2+-channels, Na+-Ca2+ exchanger and Ca2+/Mg2+-ecto ATPase (Ca2+-gating mechanism), as well as SR Ca2+-release and Ca2+-pump systems needs to be carried out in combination of gene therapy for improved beneficial effects in muscular dystrophy.

Dystrophic muscle
Dystrophin deficiency
Sarcolemmal defects
Sarcoplasmic reticular Ca2+-handling
Store-operated Ca2+-channels
Mitochondrial Ca2+-overload
Fig. 1.
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