Human neuromuscular fatigue is associated with altered Na+-K+-ATPase activity following isometric exercise

The purpose of this study was to investigate the hypothesis that reductions in Na+-K+- ATPase activity are associated with neuromuscular fatigue following isometric exercise. In control (Con) and exercised (Ex) legs, force and electromyogram were measured in 14 volunteers [age, 23.4 +/- 0.7 (SE) yr] before and immediately after (PST0), 1 h after (PST1), and 4 h after (PST4) isometric, single-leg extension exercise at ~60% of maximal voluntary contraction for 30 min using a 0.5 duty cycle (5-s contraction, 5-s rest). Tissue was obtained from vastus lateralis muscle before exercise in Con and after exercise in both the Con (PST0) and Ex legs (PST0, PST1, PST4), for the measurements of Na+-K+-ATPase activity, as determined by the 3-O-methylfluorescein phosphatase (3-O-MFPase) assay. Voluntary (maximal voluntary contraction) and elicited (10, 20, 50, 100 Hz) force was reduced 30-55% (P < 0.05) at PST0 and did not recover by PST4. Muscle action potential (M-wave) amplitude and area (measured in the vastus medialis) and 3-O-MFPase activity at PST0-Ex were less than that at PST0-Con (P < 0.05) by 37, 25, and 38%, respectively. M-wave area at PST1-Ex was also less than that at PST1-Con (P < 0.05). Changes in 3-O-MFPase activity correlated to changes in M-wave area across all time points (r = 0.38, P < 0.05, n = 45). These results demonstrate that Na+-K+- ATPase activity is reduced by sustained isometric exercise in humans from that in a matched Con leg and that this reduction in Na+-K+-ATPase activity is associated with loss of excitability as indicated by M-wave alterations.