Regulation of intracellular pH in cultured hippocampal neurons by an amiloride-insensitive Na+/H+ exchanger.

  • Raley-Susman K
  • Cragoe E
  • Sapolsky R
 et al. 
  • 1

    Readers

    Mendeley users who have this article in their library.
  • N/A

    Citations

    Citations of this article.

Abstract

Regulation of intracellular pH (pHi) in single cultured rat hippocampal neurons was investigated using the fluorescent pHi indicator dye bis-carboxyethylcarboxyfluorescein. Resting pHi was dependent on the presence of bicarbonate and external Na+ but was not altered significantly by removal of Cl- or treatment with the anion exchange inhibitor diisothiocyanatostilbene-2,2'-disulfonate. Recovery of pHi from acute acid loading was due, in large part, to a pharmacologically distinct variant of the Na+/H+ antiporter. In nominally HCO3(-)-free solutions, this recovery exhibited a saturable dose dependence on extracellular Na+ (Km = 23-26 mM) or Li+. The antiporter was activated by decreasing pHi and was unaffected by collapse of the membrane potential with valinomycin. Like the Na+/H+ antiporter described in other cell systems, the hippocampal activity was inhibited by harmaline, but in sharp contrast, neither amiloride nor its more potent 5-amino-substituted analogues were able to prevent the recovery from an acid load. These data indicate that Na(+)-dependent mechanisms dominate pHi regulation in hippocampal neurons and suggest a role for a novel variant of the Na+/H+ antiporter.

Author-supplied keywords

  • Amiloride
  • Amiloride: pharmacology
  • Animals
  • Bicarbonates
  • Carrier Proteins
  • Carrier Proteins: drug effects
  • Carrier Proteins: physiology
  • Cells
  • Cultured
  • Harmaline
  • Harmaline: pharmacology
  • Hippocampus
  • Hippocampus: chemistry
  • Hippocampus: cytology
  • Hydrogen-Ion Concentration
  • Neurons
  • Neurons: chemistry
  • Ouabain
  • Ouabain: pharmacology
  • Rats
  • Sodium-Hydrogen Antiporter

Get free article suggestions today

Mendeley saves you time finding and organizing research

Sign up here
Already have an account ?Sign in

Find this document

Authors

  • KM M Raley-Susman

  • EJ J Cragoe

  • R M Sapolsky

  • R R Kopito

Cite this document

Choose a citation style from the tabs below

Save time finding and organizing research with Mendeley

Sign up for free