Potassium, Na+,K+-pumps and fatigue in rat muscle

J Physiol. 2007 Oct 1;584(Pt 1):295-304. doi: 10.1113/jphysiol.2007.136044. Epub 2007 Aug 2.


During contractile activity, skeletal muscles undergo a net loss of cytoplasmic K(+) to the interstitial space. During intense exercise, plasma K(+) in human arterial blood may reach 8 mm, and interstitial K(+) 10-12 mm. This leads to depolarization, loss of excitability and contractile force. However, little is known about the effects of these physiological increases in extracellular K(+) ([K(+)](o)) on contractile endurance. Soleus muscles from 4-week-old rats were mounted on transducers for isometric contractions in Krebs-Ringer bicarbonate buffer containing 4-10 mm K(+), and endurance assessed by recording the rate of force decline during continuous stimulation at 60 Hz. Increasing [K(+)](o) from 4 to 8 or 10 mm and equilibrating the muscles for 40 or 20 min augmented the rate of force decline 2.4-fold and 7.2-fold, respectively (P < 0.001). The marked loss of endurance elicited by exposure to 8 or 10 mm K(+) was alleviated or significantly reduced by stimulating the Na(+),K(+)-pumps by intracellular Na(+) loading, the beta(2)-agonist salbutamol, adrenaline, calcitonin gene related peptide, insulin or repeated excitation. In conclusion, excitation-induced increase in [K(+)](o) is an important cause of high-frequency fatigue, and the Na(+),K(+)-pumps are essential for the maintenance of contractile force in the physiological range of [K(+)](o). Recordings of contractile force during continuous stimulation at 8-10 mm K(+) may be used to analyse the effects of agents or conditions influencing the excitability of working isolated muscles.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-Agonists
  • Albuterol
  • Animals
  • Calcitonin Gene-Related Peptide / metabolism
  • Electric Stimulation
  • Epinephrine / metabolism
  • In Vitro Techniques
  • Insulin / metabolism
  • Muscle Fatigue / physiology*
  • Muscle Strength / physiology*
  • Muscle, Skeletal / metabolism*
  • Physical Endurance / physiology
  • Potassium / metabolism*
  • Rats
  • Rats, Wistar
  • Sodium / metabolism
  • Sodium-Potassium-Exchanging ATPase / metabolism*


  • Adrenergic beta-Agonists
  • Insulin
  • Sodium
  • Sodium-Potassium-Exchanging ATPase
  • Calcitonin Gene-Related Peptide
  • Albuterol
  • Potassium
  • Epinephrine