title: Reduced levels of skeletal muscle Na+K+ -ATPase in McArdle disease.
abstract: We evaluated the hypothesis that impaired sarcolemmal function associated with exaggerated potassium release, impaired potassium uptake, or both may contribute to exertional fatigue and abnormal circulatory responses to exercise in McArdle disease (MD). The cellular mechanism of exertional fatigue and muscle injury in MD is unknown but likely involves impaired function of the ATPases that couple ATP hydrolysis to cellular work, including the muscle sodium potassium pump (Na+K+-ATPase). However, the concentration of muscle Na+K+ pumps in MD is not known, and no studies have related exercise increases in blood potassium concentrations to muscle Na+K+ pump levels. We measured muscle Na+K+ pumps (3H-ouabain binding) and plasma K+ in response to 20 minutes of cycle exercise in six patients with MD and in six sex-, age-, and weight-matched sedentary individuals. MD patients had lower levels of 3H-ouabain binding (231 +/- 18 pmol/g w.w., mean +/- SD, range, 210 to 251) than control subjects (317 +/- 37, range, 266 to 371, p < 0.0004), higher peak increases in plasma potassium in response to 45 +/- 7 W cycle exercise (MD, 1.00 +/- 0.15 mmol/L; control subjects, 0.48 +/- 0.09; p < 0.0001), and mean exercise heart rate responses to exercise that were 45 +/- 12 bpm greater than control subjects. Our results indicate that Na+K+ pump levels are low in MD patients compared with healthy subjects and identify a limitation of potassium reuptake that could result in sarcolemmal failure during peak rates of membrane activation and may promote exaggerated potassium-activated circulatory responses to submaximal exercise. The mechanism of the low Na+K+ pump concentrations in MD is unknown but may relate to deconditioning or to disruption of a close functional relationship between membrane ion transport and glycolysis.
authors.affiliation: Institute for Exercise and Environmental Medicine of Presbyterian Hospital, Dallas, TX 75231, USA.
authors.forename: R G
authors.initials: RG
authors.lastname: Haller
authors.forename: T
authors.initials: T
authors.lastname: Clausen
authors.forename: J
authors.initials: J
authors.lastname: Vissing
mesh_terms: D000328:Adult; D004791:Enzyme Inhibitors; D005260:Female; D006012:Glycogen Storage Disease Type V / Q000378:metabolism*; D006339:Heart Rate; D006801:Humans; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000201:enzymology*; D010042:Ouabain; D005082:Physical Exertion; D011188:Potassium / Q000097:blood; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D014316:Tritium
chemical_list: D004791:Enzyme Inhibitors; D014316:Tritium; D010042:Ouabain; D000254:Sodium-Potassium-Exchanging ATPase; D011188:Potassium