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J Physiol Volume 576, Number 1, 279-288, October 1, 2006 DOI: 10.1113/jphysiol.2006.115352
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SKELETAL MUSCLE AND EXERCISE

N-acetylcysteine attenuates the decline in muscle Na+,K+-pump activity and delays fatigue during prolonged exercise in humans

Michael J. McKenna1, Ivan Medved1, Craig A. Goodman1, Malcolm J. Brown2,3, Andrew R. Bjorksten4, Kate T. Murphy1, Aaron C. Petersen1, Simon Sostaric1 and Xiaofei Gong1

1 Muscle, Ions and Exercise Group, Centre for Ageing, Rehabilitation, Exercise and Sport, School of Human Movement, Recreation and Performance, Victoria University, Melbourne, Victoria, Australia
2 Department of Anaesthesia, Austin Health, Melbourne, Victoria, Australia
3 Department of Pharmacology, University of Melbourne, Victoria, Australia
4 Department of Anaesthesia and Pain Management, Royal Melbourne Hospital, Melbourne, Victoria, Australia

Reactive oxygen species (ROS) have been linked with both depressed Na+,K+-pump activity and skeletal muscle fatigue. This study investigated N-acetylcysteine (NAC) effects on muscle Na+,K+-pump activity and potassium (K+) regulation during prolonged, submaximal endurance exercise. Eight well-trained subjects participated in a double-blind, randomised, crossover design, receiving either NAC or saline (CON) intravenous infusion at 125 mg kg–1 h–1 for 15 min, then 25 mg kg–1 h–1 for 20 min prior to and throughout exercise. Subjects cycled for 45 min at 71% Formula , then continued at 92% Formula until fatigue. Vastus lateralis muscle biopsies were taken before exercise, at 45 min and fatigue and analysed for maximal in vitro Na+,K+-pump activity (K+-stimulated 3-O-methyfluorescein phosphatase; 3-O-MFPase). Arterialized venous blood was sampled throughout exercise and analysed for plasma K+ and other electrolytes. Time to fatigue at 92% Formula was reproducible in preliminary trials (C.V. 5.6 ± 0.6%) and was prolonged with NAC by 23.8 ± 8.3% (NAC 6.3 ± 0.5 versus CON 5.2 ± 0.6 min, P < 0.05). Maximal 3-O-MFPase activity decreased from rest by 21.6 ± 2.8% at 45 min and by 23.9 ± 2.3% at fatigue (P < 0.05). NAC attenuated the percentage decline in maximal 3-O-MFPase activity (%{Delta}activity) at 45 min (P < 0.05) but not at fatigue. When expressed relative to work done, the %{Delta}activity-to-work ratio was attenuated by NAC at 45 min and fatigue (P < 0.005). The rise in plasma [K+] during exercise and the {Delta}[K+]-to-work ratio at fatigue were attenuated by NAC (P < 0.05). These results confirm that the antioxidant NAC attenuates muscle fatigue, in part via improved K+ regulation, and point to a role for ROS in muscle fatigue.

(Received 13 June 2006; accepted after revision 7 July 2006; first published online 13 July 2006)
Corresponding author M. J. McKenna: School of Human Movement, Recreation and Performance, Victoria University, PO Box 14428, Melbourne, Victoria, Australia, 8001. Email: michael.mckenna{at}vu.edu.au




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