Potassium-transporting proteins in skeletal muscle: cellular location and fibre-type differences

Potassium (K⁺) displacement in skeletal muscle may be an important factor in the development of muscle fatigue during intense exercise. It has been shown in vitro that an increase in the extracellular K⁺ concentration ([K⁺]e) to values higher than approx. 10 m m significantly reduce force development in unfatigued skeletal muscle. Several in vivo studies have shown that [K⁺]e increases progressively with increasing work intensity, reaching values higher than 10 m m. This increase in [K⁺]e is expected to be even higher in the transverse (T)-tubules than the concentration reached in the interstitium. Besides the voltage-sensitive K⁺ (Kv) channels that generate the action potential (AP) it is suggested that the big-conductance Ca²⁺-dependent K⁺ (KCa1.1) channel contributes significantly to the K⁺ release into the T-tubules. Also the ATP-dependent K⁺ (KATP) channel participates, but is suggested primarily to participate in K⁺ release to the interstitium. Because there is restricted diffusion of K⁺ to the interstitium, K⁺ released to the T-tubules during AP propagation will be removed primarily by reuptake mediated by transport proteins located in the T-tubule membrane. The most important protein that mediates K⁺ reuptake in the T-tubules is the Na⁺,K⁺-ATPase α₂ dimers, but a significant contribution of the strong inward rectifier K⁺ (Kir2.1) channel is also suggested. The Na⁺, K⁺, 2Cl⁻ 1 (NKCC1) cotransporter also participates in K⁺ reuptake but probably mainly from the interstitium. The relative content of the different K⁺-transporting proteins differs in oxidative and glycolytic muscles, and might explain the different [K⁺]e tolerance observed.