Role of muscle in regulating extracellular [K+]

Semin Nephrol. 2005 Sep;25(5):335-42. doi: 10.1016/j.semnephrol.2005.03.009.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Extracellular Fluid / chemistry*
  • Extracellular Fluid / metabolism*
  • Homeostasis / physiology
  • Humans
  • Intracellular Fluid / chemistry
  • Intracellular Fluid / metabolism
  • Muscle, Skeletal / metabolism
  • Muscle, Skeletal / physiology*
  • Potassium / metabolism*
  • Sodium-Potassium-Exchanging ATPase / metabolism


  • Sodium-Potassium-Exchanging ATPase
  • Potassium