Expression of truncated utrophin improves pH recovery in exercising muscles of dystrophic mdx mice: a 31P NMR study.
31P NMR spectroscopy was used to study the energy metabolism of dystrophin-deficient skeletal muscle of mdx mice, an animal model of Duchenne muscular dystrophy, in which expression of a truncated form of utrophin has been obtained through transgenesis technology. Measurements of ATP, phosphocreatine (PCr), inorganic phosphates (Pi) and intracellular pH (pHi) were made at rest, during a fatigue protocol and during the subsequent recovery. Mechanical fatigue of transgenic muscles was similar to normal muscle, while mdx muscle showed larger force loss. At rest, muscles of all groups had similar values for [ATP], [PCr], [Pi] and pHi. During fatigue, [PCr] decreases mirrored [Pi] increases and were similar in all groups. The major difference between mdx muscles and the group of normal and trc-utrophin muscles concerned the values and evolution of pHi. The mdx muscles showed a more severe intracellular acidosis during exercise and a slower and incomplete post-exercise recovery of normal pHi. In contrast, in trc-utrophin muscles, the kinetics and amplitude of pHi changes were remarkably close to normal behaviour. We conclude that the impaired proton washout which is present in mdx muscles, is corrected to a great extent by the expression of trc-utrophin.
Département de Radiologie et d'Imagerie Médicale, Faculté de Médecine, Université catholique de Louvain, Bruxelles, Belgium.
J F
JF
Goudemant
N
N
Deconinck
J M
JM
Tinsley
R
R
Demeure
A
A
Robert
K E
KE
Davies
J M
JM
Gillis
D000818:Animals; D003598:Cytoskeletal Proteins / Q000737:chemistry* / Q000378:metabolism*; D006859:Hydrogen / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D009682:Magnetic Resonance Spectroscopy; D008565:Membrane Proteins / Q000737:chemistry* / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx / Q000378:metabolism / Q000502:physiology; D008822:Mice, Transgenic; D009043:Motor Activity / Q000502:physiology*; D009137:Muscular Dystrophy, Animal / Q000175:diagnosis / Q000378:metabolism / Q000503:physiopathology*; D010758:Phosphorus; D049411:Utrophin
D003598:Cytoskeletal Proteins; D008565:Membrane Proteins; C483600:Utrn protein, mouse; D049411:Utrophin; D010758:Phosphorus; D006859:Hydrogen