Dynamics and consequences of potassium shifts in skeletal muscle and heart during exercise

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 KC 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 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.