Role of muscle in regulating extracellular [K+].
There is a positive association between diets rich in potassium, control of blood pressure, and prevention of stroke. Extracellular [K+] is regulated closely to maintain normal membrane excitability by the concerted regulatory responses of muscle and kidney. Although kidney is responsible for ultimately matching K+ output to K+ intake each day, muscle contains more than 90% of the body's K+ and can buffer changes in extracellular fluid [K+] by either acutely taking up extracellular fluid K+ or releasing intracellular fluid K+ from muscle. It long has been assumed that the changes in muscle K+ transport are a function of sodium pump (Na,K-adenosine triphosphatase [Na, K-ATPasel]) abundance, especially that of the alpha2 isoform, which predominates in skeletal muscle. To test the physiologic significance of changes in muscle Na,K-ATPase expression, we developed the K+ clamp, which measures insulin-stimulated cellular K+ uptake in vivo in the conscious rat. By using the K+ clamp we discovered that significant insulin resistance to cell K+ uptake occurs as follows: (1) early in K+ deprivation before a decrease in muscle sodium pump pool size, and (2) during glucocorticoid treatment, which increases muscle Na,K-ATPase alpha2 levels greater than 50%. We also discovered that adaptation of renal and extrarenal K+ handling to altered K+ balance often occurs without changes in plasma [K+], supporting a feedforward mechanism involving K+ sensing in the splanchnic bed and adjustment of K+ handling. These findings establish the advantage of combining molecular analyses of Na,K-ATPase expression and activity with systems analyses of cellular K+ uptake and excretion in vivo to reveal regulatory mechanisms operating to control K+ homeostasis.
McDonough
Alicia A
AA
Department of Physiology and Biophysics, University of Southern California Keck School of Medicine, Los Angeles, CA 90089-9142, USA.
Youn
Jang H
JH
D000818:Animals; D045604:Extracellular Fluid / Q000737:chemistry* / Q000378:metabolism*; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D007424:Intracellular Fluid / Q000737:chemistry / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism / Q000502:physiology*; D011188:Potassium / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
D000254:Sodium-Potassium-Exchanging ATPase; D011188:Potassium