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ENVIRONMENTAL, EXERCISE AND RESPIRATORY PHYSIOLOGY

Ionic mechanisms of excitation-induced regulation of Na⁺-K⁺-ATPase mRNA expression in isolated rat EDL muscle

¹Muscle, Ions and Exercise Group, School of Human Movement, Recreation and Performance, Centre for Ageing, Rehabilitation and Sport Science, Victoria University of Technology, Melbourne, Australia; and ²Institute of Physiology and Biophysics, University of Aarhus, Århus, Denmark

Submitted 4 October 2005 ; accepted in final form 14 December 2005

This study investigated the effects of electrical stimulation on Na⁺-K⁺-ATPase isoform mRNA, with the aim to identify factors modulating Na⁺-K⁺-ATPase mRNA in isolated rat extensor digitorum longus (EDL) muscle. Interventions designed to mimic exercise-induced increases in intracellular Na⁺ and Ca²⁺ contents and membrane depolarization were examined. Muscles were mounted on force transducers and stimulated with 60-Hz 10-s pulse trains producing tetanic contractions three times at 10-min intervals. Ouabain (1.0 mM, 120 min), veratridine (0.1 mM, 30 min), and monensin (0.1 mM, 30 min) were used to increase intracellular Na⁺ content. High extracellular K⁺ (13 mM, 60 min) and the Ca²⁺ ionophore A-23187 (0.02 mM, 30 min) were used to induce membrane depolarization and elevated intracellular Ca²⁺ content, respectively. Muscles were analyzed for Na⁺-K⁺-ATPase ₁–₃ and ₁–₃ mRNA (real-time RT-PCR). Electrical stimulation had no immediate effect on Na⁺-K⁺-ATPase mRNA; however at 3 h after stimulation, it increased ₁, ₂, and ₃ mRNA by 223, 621, and 892%, respectively (P = 0.010), without changing mRNA. Ouabain, veratridine, and monensin increased intracellular Na⁺ content by 769, 724, and 598%, respectively (P = 0.001) but did not increase mRNA of any isoform. High intracellular K⁺ concentration elevated ₁ mRNA by 160% (P = 0.021), whereas A-23187 elevated ₃ mRNA by 123% (P = 0.035) but reduced ₁ mRNA by 76% (P = 0.001). In conclusion, electrical stimulation induced subunit-specific increases in Na⁺-K⁺-ATPase mRNA in isolated rat EDL muscle. Furthermore, Na⁺-K⁺-ATPase mRNA appears to be regulated by different stimuli, including cellular changes associated with membrane depolarization and increased intracellular Ca²⁺ content but not increased intracellular Na⁺ content.

gene expression; Na⁺-K⁺ pump; skeletal muscle

This article has been cited by other articles:

				R. J. Aughey, K. T. Murphy, S. A. Clark, A. P. Garnham, R. J. Snow, D. Cameron-Smith, J. A. Hawley, and M. J. McKenna Muscle Na+-K+-ATPase activity and isoform adaptations to intense interval exercise and training in well-trained athletes J Appl Physiol, July 1, 2007; 103(1): 39 - 47. [Abstract] [Full Text] [PDF]