The alteration of calcium homeostasis in adult dystrophic mdx muscle fibers is worsened by a chronic exercise in vivo.
Chronic exercise in vivo aggravates dystrophy in mdx mice. Calcium homeostasis was evaluated ex vivo by micro-spectrofluorometry on tendon-to-tendon dissected extensor digitorum longus (EDL) muscle fibers. Resting cytosolic calcium ([Ca2+]i) and sarcolemmal permeability through Gd3+ -sensitive mechanosensitive calcium (MsCa) channel were significantly higher in mdx vs. wild-type fibers. The exercise further enhanced [Ca2+]i in mdx fibers and increased sarcolemmal permeability by activating nifedipine-sensitive leak calcium channels. The two genotypes did not differ in caffeine sensitivity and in the excitation-calcium release (ECaR) coupling mechanism by K+ depolarization. The exercise produced a similar adaptation of activation curve of ECaR and of sensitivity to caffeine. However, the inactivation of ECaR of mdx fibers did not adapt to exercise. No fiber phenotype transition occurred in exercised muscle. We provide the first evidence that an in vivo exercise worsens the impaired calcium homeostasis of dystrophic fibers, supporting the role of enhanced calcium entrance in dystrophic progression.
Unit of Pharmacology, Department of Pharmacobiology, Faculty of Pharmacy, University of Bari, Bari, Italy.
Bodvael
B
Fraysse
Antonella
A
Liantonio
Michela
M
Cetrone
Rosa
R
Burdi
Sabata
S
Pierno
Antonio
A
Frigeri
Michela
M
Pisoni
Claudia
C
Camerino
Annamaria
A
De Luca
D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002413:Cations, Divalent / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004594:Electrophysiology; D005552:Forelimb / Q000503:physiopathology; D018737:Hand Strength; D006706:Homeostasis; D007150:Immunohistochemistry; D051379:Mice; D018101:Mice, Inbred mdx; D009043:Motor Activity; D009119:Muscle Contraction / Q000502:physiology; D018485:Muscle Fibers, Skeletal / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000502:physiology; D009137:Muscular Dystrophy, Animal / Q000378:metabolism / Q000503:physiopathology*; D018995:Myosin Heavy Chains / Q000378:metabolism; D009994:Osmolar Concentration; D010539:Permeability; D012508:Sarcolemma / Q000378:metabolism; D013997:Time Factors; D014034:Toes
D002413:Cations, Divalent; D002110:Caffeine; D018995:Myosin Heavy Chains; D002118:Calcium