Dynamics and consequences of potassium shifts in skeletal muscle and heart during exercise.
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Physiol. Rev. 80 (4): 1411--1481 (October 2000)

Since it became clear that K$^+$ shifts with exercise are extensive and can cause more than a doubling of the extracellular K$^+$ (K$^+$(s)) as reviewed here, it has been suggested that these shifts may cause fatigue through the effect on muscle excitability and action potentials (AP). The cause of the K$^+$ shifts is a transient or long-lasting mismatch between outward repolarizing K$^+$ currents and K$^+$ influx carried by the Na$^+$-K$^+$ pump. Several factors modify the effect of raised K$^+$(s) during exercise on membrane potential (E(m)) and force production. 1) Membrane conductance to K$^+$ is variable and controlled by various K$^+$ channels. Low relative K$^+$ conductance will reduce the contribution of K$^+$(s) to the E(m). In addition, high Cl$^-$ conductance may stabilize the E(m) during brief periods of large K$^+$ shifts. 2) The Na$^+$-K$^+$ pump contributes with a hyperpolarizing current. 3) Cell swelling accompanies muscle contractions especially in fast-twitch muscle, although little in the heart. This will contribute considerably to the lowering of intracellular K$^+$ (K$^+$(c)) and will attenuate the exercise-induced rise of intracellular Na$^+$ (Na$^+$(c)). 4) The rise of Na$^+$(c) is sufficient to activate the Na$^+$-K$^+$ pump to completely compensate increased K$^+$ release in the heart, yet not in skeletal muscle. In skeletal muscle there is strong evidence for control of pump activity not only through hormones, but through a hitherto unidentified mechanism. 5) Ionic shifts within the skeletal muscle t tubules and in the heart in extracellular clefts may markedly affect excitation-contraction coupling. 6) Age and state of training together with nutritional state modify muscle K$^+$ content and the abundance of Na$^+$-K$^+$ pumps. We conclude that despite modifying factors coming into play during muscle activity, the K$^+$ shifts with high-intensity exercise may contribute substantially to fatigue in skeletal muscle, whereas in the heart, except during ischemia, the K$^+$ balance is controlled much more effectively.
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