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 alpha beta heterodimers during potassium deprivation. The alpha 2 (not the alpha 1) sodium pump isoform is specifically decreased and beta 1 and/or beta 2 decreases in a muscle-fibre-dependent manner. The specific loss of K+ from skeletal muscle is probably a consequence of the fact that the alpha 2 isoform predominates in this tissue. In tissues such as heart, where alpha 2-type pumps are only a minor fraction of the sodium pumps, the activity of the ubiquitous alpha 1 isoform maintains intracellular Na+ and K+ at control levels, despite the fact that alpha 2 levels decrease by 50%. Analysis of the time course of change in alpha 2 mRNA vs. protein during K+ deprivation indicates that there is both a decrease in alpha 2 synthesis and an increase in alpha 2 degradation. The apparent time-lag during potassium deprivation between the early decreases in both surface alpha 2-type sodium pump number (assessed by 3H-ouabain binding) and intracellular K+, and the later decrease in total pool size of alpha 2, suggests the hypothesis that there may be an early internalization of alpha 2 sodium pumps to endosomal pools, followed by a degradation of these internalized pumps, contributing to the decrease in total alpha 2 pool size. The signals mediating this specific response to hypokalemia, and those mediating the restoration of muscle K+ stores remain to be determined.
McDonough
A A
AA
Department of Physiology and Biophysics, University of Southern California School of Medicine, Los Angeles 90033, USA.
Thompson
C B
CB
D000818:Animals; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000503:physiopathology*; D011191:Potassium Deficiency / Q000503:physiopathology*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*
D000254:Sodium-Potassium-Exchanging ATPase