Excitability of the T-tubular system in rat skeletal muscle: roles of K+ and Na+ gradients and Na+–K+ pump activity

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 m m significantly reduced twitch force. Between 10 and 50 m m Na + , the reduction in force depended on [Na + ] i , the twitch force at 40 m m K + being 22 ± 4 and 54 ± 9% (of control force) at a [Na + ] i of 10 and 20 m m , 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.