ATP from glycolysis is required for normal sodium homeostasis in resting fast-twitch rodent skeletal muscle.
Myocellular sodium homeostasis is commonly disrupted during critical illness for unknown reasons. Recent data suggest that changes in intracellular sodium content and the amount of ATP provided by glycolysis are closely related. The role of glycolysis and oxidative phosphorylation in providing fuel to the Na(+)-K(+) pump was investigated in resting rat extensor digitorum longus muscles incubated at 30 degrees C for 1 h. Oxidative inhibition with carbonyl cyanide m-chlorophenylhydrazone, known as CCCP (0.2 microM), or by hypooxygenation did not alter myocellular sodium or potassium content ([Na(+)](i), [K(+)](i), respectively), whereas treatment with iodoacetic acid (0.3 mM), which effectively blocked glycolysis, dramatically increased [Na(+)](i) and the [Na(+)](i)/[K(+)](i) ratio. Experiments using ouabain and measurements of myocellular high-energy phosphates indicate that Na(+)-K(+)-ATPase activity is only impaired when glycolysis is inhibited. The data suggest that normal glycolysis is required to regulate intracellular sodium in fast-twitch skeletal muscles, because it is the predominant source of the fuel for the Na(+)-K(+)-ATPase.
Okamoto
K
K
Laboratories for Surgical Metabolism and Nutrition, Department of Surgery, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Wang
W
W
Rounds
J
J
Chambers
E A
EA
Jacobs
D O
DO
D000244:Adenosine Diphosphate / Q000378:metabolism; D000249:Adenosine Monophosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone / Q000494:pharmacology; D003402:Creatine Kinase / Q000378:metabolism; D005934:Glucagon / Q000494:pharmacology; D006003:Glycogen / Q000378:metabolism; D006019:Glycolysis; D006706:Homeostasis; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D019344:Lactic Acid / Q000096:biosynthesis; D008297:Male; D018656:Muscle Fibers, Fast-Twitch / Q000187:drug effects / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D010085:Oxidative Phosphorylation; D010725:Phosphocreatine / Q000378:metabolism; D011188:Potassium / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000378:metabolism*; D013047:Specific Pathogen-Free Organisms
D010725:Phosphocreatine; D019344:Lactic Acid; D000249:Adenosine Monophosphate; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D006003:Glycogen; D005934:Glucagon; D012964:Sodium; D007770:L-Lactate Dehydrogenase; D003402:Creatine Kinase; D011188:Potassium