REDUCED LEVELS OF SKELETAL-MUSCLE NA-ATPASE IN MCARDLE-DISEASE(K+)

We evaluated the hypothesis that impaired sarcolemmal function associa ted with exaggerated potassium release, impaired potassium uptake, or both may contribute to exertional fatigue and abnormal circulatory res ponses to exercise in McArdle disease (MD). The cellular mechanism of exertional fatigue and muscle injury in MD is unknown but likely invol ves impaired function of the ATPases that couple ATP hydrolysis to cel lular 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 conc entrations to muscle Na+K+ pump levels. We measured muscle Na+K+ pumps (H-3-ouabain binding) and plasma K+ in response to 20 minutes of cycl e exercise in six patients with MD and in six sex-, age-, and weight-m atched sedentary individuals. MD patients had lower levels of H-3-ouab ain binding (231 +/- 18 pmol/g w.w., mean +/- SD, range, 210 to 251) t han control subjects (317 +/- 37, range, 266 to 371, p < 0.0004), high er 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 we re 45 +/- 12 bpm greater than control subjects. Our results indicate t hat Na+K+ pump levels are low in MD patients compared with healthy sub jects and identify a Limitation of potassium reuptake that could resul t in sarcolemmal failure during peak rates of membrane activation and may promote exaggerated potassium-activated circulatory responses to s ubmaximal 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 gl ycolysis.