Programme Contents

N-acetylcysteine infusion enhances skeletal muscle Na⁺,K⁺-ATPase activity and plasma K⁺ regulation, and delays fatigue, during prolonged submaximal exercise in well-trained individuals

The production of reactive oxygen species (ROS) in skeletal muscle has been linked with muscle fatigue (for review see Reid, 2001). Recently, we showed that intravenous infusion of the antioxidant N-acetylcysteine (NAC) increased each of muscle NAC (total and reduced), cysteine and glutathione (reduced) and improved prolonged submaximal exercise performance in well-trained individuals (Medved et al., 2004). We have found depressed Na⁺,K⁺-ATPase activity in skeletal muscle during exercise, which may contribute to disturbed muscle ionic homeostasis and fatigue (Leppik et al., 2004). This study investigated whether ROS may be involved in this process, by examining the effect of NAC infusion on skeletal muscle Na⁺,K⁺-ATPase activity and potassium (K⁺) regulation during prolonged submaximal endurance exercise, in well trained individuals.

Eight well-trained subjects participated in a double blind, randomised, crossover design study, receiving either an NAC or saline (CON) infusion into a superficial forearm vein (Medved et al., 2003). NAC was intravenously infused at 125 mg.kg^-1.hr^-1 for 15 min, then 25 mg.kg^-1.hr^-1 for 20 min prior to and throughout exercise, which was continued until fatigue. Subjects completed cycling exercise comprising 45 min at 70% VO_2peak, then to fatigue at 90% VO_2peak. Muscle biopsies were taken from the vastus lateralis before exercise, at 45 min and at fatigue and analysed for maximal in vitro Na⁺,K⁺-ATPase activity (maximal K⁺-stimulated 3-O-methyfluorescein phosphatase, 3-O-MFPase). Blood was sampled at pre-infusion, immediately prior to exercise, during exercise at 15, 30, 45 min and at fatigue. Blood was analysed for plasma [K⁺] as well as blood haemoglobin concentration ([Hb]) and hematocrit (Hct).

Time to fatigue at 90% VO_2peak was reproducible in preliminary trials (CV 5.6±0.6%) and with NAC was enhanced by 20.8±9.1% (NAC 6.4±0.6 vs CON 5.3±0.7 min, P<0.05) (Medved et al., 2004). Maximal 3-O-MFPase activity decreased by 21.6±2.8% at 45 min and by 23.9±2.3% at fatigue when compared to rest (P<0.05). NAC attenuated the percentage change in maximal 3-O-MFPase activity at 45 min (P<0.05) compared to control but not at fatigue. However, the change in 3-O-MFPase activity to work ratio was attenuated by NAC both at 45 min and at fatigue (P<0.005). The rise in plasma [K⁺] and plasma Δ[K⁺]-to-work ratio during exercise were both attenuated by NAC (P<0.05). There was no significant correlation between time to fatigue and each of maximal 3-O-MFPase, rise in plasma [K⁺] and plasma Δ[K⁺]-to-work ratio.

In conclusion, our data show that NAC infusion in well-trained individuals attenuated the depression in muscle Na⁺,K⁺-ATPase and enhanced K⁺ regulation, which may be important in delaying fatigue during prolonged submaximal exercise. This suggests that ROS play a role in skeletal muscle fatigue and specifically in Na⁺,K⁺-ATPase regulation and K⁺ regulation during submaximal exercise.

Leppik, J.A., Aughey, R.J., Medved, I., Fairwhether, I., Carey, M.F. & McKenna, M.J. (2004) Journal of Applied Physiology, 97, 1414-1423.

Medved, I., Brown, M.J., Bjorksten, A.R., Leppik, J.A., Sostaric, S. & McKenna, M.J. (2003) Journal of Applied Physiology, 94, 1572-1582.

Medved, I., Brown, M.J., Bjorksten, A.R., Murphy, K.T., Petersen, A.C., Sostaric, S., Gong, X. & McKenna, M.J. (2004) Journal of Applied Physiology, 97, 1477-1485.

Reid, M.B. (2001) Journal of Applied Physiology, 90, 724-731.