Experimentally induced defects of mitochondrial metabolism in rat skeletal muscle. Biological effects of the mitochondrial uncoupling agent 2,4-dinitrophenol.
Infusion of dinitrophenol intra-arterially into rat hind limb caused an irreversible failure of isometric twitch tension and the induction of a severe progressive contracture. Metabolite analysis of muscle in which the twitch response had grossly fatigued revealed low levels of ATP and phosphocreatine together with lactate accumulation. Studies using 31P-n.m.r. confirmed the decrease in ATP and creatine phosphate concentrations and indicated a fall in intracellular pH. It is concluded that dinitrophenol-induced myopathy does not represent a good model for the human mitochondrial myopathic condition as has been previously suggested.
D019297:2,4-Dinitrophenol; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D004140:Dinitrophenols / Q000494:pharmacology*; D004195:Disease Models, Animal; D004558:Electric Stimulation; D007537:Isometric Contraction; D009682:Magnetic Resonance Spectroscopy; D008931:Mitochondria, Muscle / Q000187:drug effects / Q000378:metabolism*; D009135:Muscular Diseases / Q000378:metabolism; D010725:Phosphocreatine / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D014475:Uncoupling Agents / Q000494:pharmacology*
D004140:Dinitrophenols; D014475:Uncoupling Agents; D010725:Phosphocreatine; D000255:Adenosine Triphosphate; D019297:2,4-Dinitrophenol