Effects of membrane depolarization and changes in extracellular [K+] on the Ca2+ transients of fast skeletal muscle fibers. Implications for muscle fatigue
Abstract 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 mm 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 mm. 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(+) (K(v)) channels that generate the action potential (AP) it is suggested that the big-conductance Ca(2+)-dependent K(+) (K(Ca)1.1) channel contributes significantly to the K(+) release into the T-tubules. Also the ATP-dependent K(+) (K(ATP)) 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 alpha(2) 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.