Intensive contractile activity is associated with a significant loss of K⁺ from the working muscle fibres, causing an increase in interstitial and T-tubular [K⁺]. The ensuing depolarisation may interfere with fibre excitability and cause fatigue (Sejersted & Sjogaard, 2000). On the sarcolemma, a work-induced increase in Na⁺-K⁺ pump activity reduces the depressing effect of high K⁺ on excitability (Overgaard & Nielsen, 2001). Because the ratio between membrane area and T-tubular volume is very large, the build-up of K⁺ is likely to be augmented in the T-tubules. Little is known, however, about the significance of elevated extracellular K⁺ and Na⁺-K⁺ pump activity for the excitability of the T-tubular membrane. To examine this, the sarcolemma of single fibres from rat extensor digitorum longus was mechanically removed in such a way that the T-tubular system was sealed off and polarised, making it possible to elicit contractions by setting up action potentials in the T-tubular system with electrical stimulation (Posterino et al. 2000). The fibres were placed on an isometric transducer at room temperature and stimulated with 2 ms square pulses (50 V cm^-1). The activity of the Na⁺-K⁺ pump was manipulated by use of solutions with 10 to 50 mM Na⁺. Animals were killed humanely.

In control solution that mimicked the intracellular environment (30 mM Na⁺ and 113 mM K⁺, for details, see Posterino et al. 2000), twitch force was 36 ± 3 % of the force induced by saturating levels of Ca²⁺ (n = 9). Figure 1 shows that lowering the chemical gradient for K⁺ by reducing K⁺ in the buffer to 30 or 40 mM produced a large force deficit, indicating a reduction in T-tubular excitability. The reduction in force depended, however, on the [Na⁺] of the solution. Thus at 30 K⁺ the force produced at 50 mM Na⁺ was 2-fold larger than at 20 mM Na⁺ (P < 0.03, paired t test). At 40 mM K⁺ a similar effect was obtained by increasing Na⁺ from 10 to 20 mM. These results indicate that the sensitivity of T-tubular excitability to a lowering of the chemical gradient for K⁺ can be reduced by increasing the activity of the Na⁺-K⁺ pump. This suggests that during exercise, the increase in the activity of muscle Na⁺-K⁺ pumps protects T-tubular excitability against the depressing effect of elevated extracellular K⁺.

All procedures accord with current National and local guidelines.