A quantitative study of bioenergetics in skeletal muscle lacking utrophin and dystrophin.
Muscle energetics and function were investigated in the hindlimb of mice lacking dystrophin (mdx), utrophin and dystrophin (utr-dys) and controls (C57Bl/10) using 31P and 1H magnetic resonance techniques, electrical nerve stimulation and direct biochemical analysis. At rest, [adenosine triphosphate] and [total creatine] were lowest in utr-dys, while [inorganic phosphate] was elevated. Calculated [adenosine diphosphate] was 3-fold higher in mdx and 5-fold higher in utr-dys than in controls, consistent with an increased adenosine triphosphate requirement for ion pump activity. During stimulation, force production was low only in utr-dys, and this was reflected in the bioenergetic changes. Initial recovery rates of [phosphocreatine] and [adenosine diphosphate] after stimulation were rapid in all groups, indicative of normal mitochondrial adenosine triphosphate production in utr-dys and mdx. Recovery of pH was slow in utr-dys. The data indicate that the severe abnormalities which are present in the absence of utrophin and dystrophin leave basic muscle energetics intact and appear confined to processes involving the sarcolemma.
Cole
M A
MA
MRC Biochemical and Clinical Magnetic Resonance Unit, Department of Biochemistry, South Parks Road, Oxford OX1 3QU, UK.
Rafael
J A
JA
Taylor
D J
DJ
Lodi
R
R
Davies
K E
KE
Styles
P
P
D000244:Adenosine Diphosphate / Q000032:analysis; D000255:Adenosine Triphosphate / Q000032:analysis; D000818:Animals; D003598:Cytoskeletal Proteins / Q000235:genetics*; D016189:Dystrophin / Q000235:genetics*; D004734:Energy Metabolism / Q000502:physiology*; D005223:Fats / Q000032:analysis; D006863:Hydrogen-Ion Concentration; D009682:Magnetic Resonance Spectroscopy; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D018482:Muscle, Skeletal / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology; D009137:Muscular Dystrophy, Animal / Q000378:metabolism* / Q000473:pathology; D010725:Phosphocreatine / Q000032:analysis; D010759:Phosphorus Isotopes; D011522:Protons; D049411:Utrophin
D003598:Cytoskeletal Proteins; D016189:Dystrophin; D005223:Fats; D008565:Membrane Proteins; D010759:Phosphorus Isotopes; D011522:Protons; C483600:Utrn protein, mouse; D049411:Utrophin; D010725:Phosphocreatine; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate