Skeletal muscle regulates extracellular potassium

Maintaining extracellular fluid (ECF) K+ concentration ([K+]) within a narrow range is accomplished by the concerted responses of the kidney, which matches K+ excretion to K+ intake, and skeletal muscle, the main intracellular fluid (ICF) store of K+, which can rapidly buffer ECF [K+]. In both systems, homologous P-type ATPase isoforms are key effectors of this homeostasis. During dietary K+ deprivation, these P-type ATPases are regulated in opposite directions: increased abundance of the H,K-ATPase “colonic” isoform in the renal collecting duct drives active K+ conservation while decreased abundance of the plasma membrane Na,K-ATPase α2-isoform leads to the specific shift of K+ from muscle ICF to ECF. The skeletal muscle response is isoform and muscle specific: α2 and β2, not α1 and β1, levels are depressed, and fast glycolytic muscles lose >90% α2, whereas slow oxidative muscles lose ∼50%; however, both muscle types have the same fall in cellular [K+]. To understand the physiological impact, we develope...