Role of skeletal muscle sodium pumps in the adaptation to potassium deprivation.

Skeletal muscle is specialized to lose K + to the extracellular fluid during potassium deprivation which buffers the fall in plasma K + concentration. While it remains to be determined whether K + efflux from muscle is altered during K + deprivation, active K + uptake driven by sodium pumps is significantly depressed. The activity of sodium pumps in skeletal muscle does not increase during K + depletion despite elevated intracellular Na + , a strong stimulus to increase activity in other cells There is a decrease in the total pool size of sodium pump αβ heterodimers during potassium deprivation. The α2 (not the α1) sodium pump isoform is specifically decreased and β1 and/or β2 decreases in a muscle-fibre-dependent manner. The specific loss of K + from skeletal muscle is probably a consequence of the fact that the α2 isoform predominates in this tissue. In tissues such as heart, where α2-type pumps are only a minor fraction of the sodium pumps, the activity of the ubiquitous α1 isoform maintains intracellular Na + and K + at control levels, despite the fact that α2 levels decrease by 50%. Analysis of the time course of change in α2 mRNA vs. protein during K + deprivation indicates that there is both a decrease in α2 synthesis and an increase in α2 degradation. The apparent time-lag during potassium deprivation between the early decreases in both surface α2-type sodium pump number (assessed by 3 H-ouabain binding) and intracellular K + , and the later decrease in total pool size of α2, suggests the hypothesis that there may be an early internalization of α2-type sodium pumps to endosomal pools, followed by a degradation of these internalized pumps, contributing to the decrease in total α2 pool size. The signals mediating this specific response to hypokalemia. and those mediating the restoration of muscle K + stores remain to be determined