Ion gradients and contractility in skeletal muscle: the role of active Na+, K+ transport.

Intensive contractile activity is associated with a significant net loss of K+ and a comparable gain of Na+ in the working muscle fibres. This leads to an increase in the interstitial and T-tubular K+ concentration and to a decrease in the T-tubular Na+ concentration. It is well established that the exposure of muscles to high extracellular K+ or low extracellular Na+ inhibits contractile performance. More importantly, the combination of high extracellular K+ and low extracellular Na+ has a much more pronounced inhibitory effect on force than the sum of the individual effects of the two ions. The inhibitory effects of high extracellular K+ or low extracellular Na+ can be alleviated within 5-10 min by acute hormonal stimulation of the Na+, K+ pump. In contrast, reductions in the capacity for active Na+, K+ transport by pre-incubation of isolated muscles with ouabain or by prior K+ depletion of the animals significantly decreases contractile endurance during high-frequency electrical stimulation. Thus, muscles from K(+)-depleted rats exhibiting a 54% reduction in Na+, K+ pump concentration showed a 110% increase in force decline during 30 s of 60 Hz stimulation. Reducing the Na+, K+ pump capacity to a similar extent by pre-incubation with ouabain led to a comparable decrease in endurance. Moreover, reductions in the Na+, K+ pump capacity were associated with an increased intracellular accumulation of Na+ during electrical stimulation. These observations support the notion that excitation-induced decreases in Na+, K+ gradients contribute to fatigue during intensive exercise and suggest that the capacity for active Na+, K+ transport is a determining factor for contractile endurance.