Intracellular alkalosis induced by increasing extracellular potassium. Ionic dependence and effects of amiloride and DIDS

Miner Electrolyte Metab. 1990;16(4):197-201.


The intracellular alkalinization produced when extracellular potassium concentration is increased above its normal levels was studied in the rat diaphragm muscle by determination of the steady-state distribution of [14C]-5,5-dimethyl-2,4-oxazolidinedione (DMO). Replacement of external Na+ with sucrose and Mg2+ or N-methyl-D-glucamine prevented the rise in intracellular pH. Amiloride (1 mM) also abolished the elevation of intracellular pH, while the removal of external Cl- (replaced by gluconate) or addition of 0.1 mM 4-acetamido-4'-diisothyocyanostilbene-2,2-disulfonic acid (DIDS) did not prevent intracellular alkalinization from taking place. These results suggest that in the rat diaphragm muscle a Na(+)-dependent, amiloride-sensitive transport mechanism, perhaps Na+/H+ exchange, plays a major role in the K(+)-induced intracellular alkalinization. This mechanism might account for the metabolic acidosis produced by hyperkalemia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid
  • 4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid / analogs & derivatives*
  • 4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid / pharmacology
  • Alkalosis / chemically induced*
  • Amiloride / pharmacology*
  • Animals
  • Cell Membrane / drug effects
  • Cell Membrane / metabolism
  • Chlorides / metabolism
  • Diaphragm / drug effects*
  • Diaphragm / metabolism
  • Hydrogen-Ion Concentration
  • Male
  • Muscles / drug effects
  • Muscles / metabolism
  • Potassium / toxicity*
  • Rats
  • Rats, Inbred Strains
  • Sodium / pharmacology


  • Chlorides
  • 4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid
  • Amiloride
  • Sodium
  • 4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid
  • Potassium