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J Physiol Volume 557, Number 1, 133-146, May 15, 2004 DOI: 10.1113/jphysiol.2003.059014
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Excitability of the T-tubular system in rat skeletal muscle: roles of K+ and Na+ gradients and Na+–K+ pump activity

O. B. Nielsen1, N. Ørtenblad2, G. D. Lamb2 and D. G. Stephenson2

1 Department of Physiology, University of Aarhus, DK-8000 Århus C, Denmark2 Department of Zoology, La Trobe University, Bundoora, Victoria 3086, Australia

Strenuous exercise causes an increase in extracellular [K+] and intracellular Na+ ([Na+]i) of working muscles, which may reduce sarcolemma excitability. The excitability of the sarcolemma is, however, to some extent protected by a concomitant increase in the activity of muscle Na+–K+ pumps. The exercise-induced build-up of extracellular K+ is most likely larger in the T-tubules than in the interstitium but the significance of the cation shifts and Na+–K+ pump for the excitability of the T-tubular membrane and the voltage sensors is largely unknown. Using mechanically skinned fibres, we here study the role of the Na+–K+ pump in maintaining T-tubular function in fibres with reduced chemical K+ gradient. The Na+–K+ pump activity was manipulated by changing [Na+]i. The responsiveness of the T-tubules was evaluated from the excitation-induced force production of the fibres. Compared to control twitch force in fibres with a close to normal intracellular [K+] ([K+]i), a reduction in [K+]i to below 60 mM significantly reduced twitch force. Between 10 and 50 mM Na+, the reduction in force depended on [Na+]i, the twitch force at 40 mM K+ being 22 ± 4 and 54 ± 9% (of control force) at a [Na+]i of 10 and 20 mM, respectively (n= 4). Double pulse stimulation of fibres at low [K+]i showed that although elevated [Na+]i increased the responsiveness to single action potentials, it reduced the capacity of the T-tubules to respond to high frequency stimulation. It is concluded that a reduction in the chemical gradient for K+, as takes place during intensive exercise, may depress T-tubular function, but that a concomitant exercise-induced increase in [Na+]i protects T-tubular function by stimulating the Na+–K+ pump.

(Received 2 December 2003; accepted after revision 15 March 2004; first published online 19 March 2004)
Corresponding author O. B. Nielsen: Department of Physiology, University of Aarhus, DK-8000 Århus C, Denmark. Email: obn{at}fi.au.dk




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