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Received December 2, 2003
Revised January 6, 2004
Accepted after revision March 15, 2004
1 University of Aarhus
2 University of Southern Denmark, Odense
3 La Trobe University
* To whom correspondence should be addressed. E-mail: obn{at}fi.au.dk.
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 to 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 despite the increase in force, elevated [Na+]i 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.
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