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

  • Raley-Susman K
  • Cragoe E
  • Sapolsky R
 et al. 
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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/*pharmacology
  • Animals
  • Bicarbonates
  • Carrier Proteins/drug effects/*physiology
  • Cells
  • Cultured
  • Harmaline/pharmacology
  • Hippocampus/*chemistry/cytology
  • Hydrogen-Ion Concentration
  • Neurons/*chemistry
  • Ouabain/pharmacology
  • Rats
  • Sodium-Hydrogen Antiporter

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  • K M Raley-Susman

  • E J Cragoe

  • R M Sapolsky

  • R R Kopito

  • E J Cragoe Jr.

  • R M Sapolsky

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