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 alpha(2)-isoform leads to the specific shift of K(+) from muscle ICF to ECF. The skeletal muscle response is isoform and muscle specific: alpha(2) and beta(2), not alpha(1) and beta(1), levels are depressed, and fast glycolytic muscles lose >90% alpha(2), whereas slow oxidative muscles lose ~50%; however, both muscle types have the same fall in cellular [K(+)]. To understand the physiological impact, we developed the "K(+) clamp" to assess insulin-stimulated cellular K(+) uptake in vivo in the conscious rat by measuring the exogenous K(+) infusion rate needed to maintain constant plasma [K(+)] during insulin infusion. Using the K(+) clamp, we established that K(+) deprivation leads to near-complete insulin resistance of cellular K(+) uptake and that this insulin resistance can occur before any decrease in plasma [K(+)] or muscle Na(+) pump expression. These studies establish the advantage of combining molecular analyses of P-type ATPase expression with in vivo analyses of cellular K(+) uptake and excretion to determine mechanisms in models of disrupted K(+) homeostasis.
McDonough
Alicia A
AA
Department of Physiology and Biophysics, University of Southern California Keck School of Medicine, Los Angeles, California 90089-9142, USA. mcdonoug@hsc.usc.edu
Thompson
Curtis B
CB
Youn
Jang H
JH
D000818:Animals; D001774:Blood Chemical Analysis / Q000379:methods; D005110:Extracellular Space / Q000378:metabolism*; D006801:Humans; D007668:Kidney / Q000502:physiology; D018482:Muscle, Skeletal / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
D000254:Sodium-Potassium-Exchanging ATPase; D011188:Potassium