title: Ionic mechanisms of intracellular pH regulation in the nervous system.
abstract: Two separate mechanisms responsible for intracellular pH (pHi) regulation in neuronal membranes of the nervous system have been studied so far: they are Na+/H+ and Na+-H+-HCO3-/Cl- exchange. The involvement of these mechanisms in pHi regulation of neurons and glial cells has been investigated in the leech central nervous system using ion-selective microelectrodes. The amiloride-sensitive Na+/H+ exchange is the predominant mechanism of pHi regulation in nominally HCO3- free, Hepes-buffered saline of both neurons and glial cells of this nervous system. In the presence of CO2-HCO3- buffer, however, the SITS-sensitive Na+-H+-HCO3-/Cl- exchanger contributes to acid extrusion in neurons and probably also in glial cells. Unlike neuronal pHi, glial pHi increases when Hepes is replaced by CO2-HCO3- as the extracellular buffer, and decreases again on return to Hepes buffer. The glial alkalinization occurs in the opposite direction, as would be expected from the CO2 movement across the cell membrane and its hydration to form carbonic acid which dissociates into H+ and HCO3- ions. The expected acidification, however, is observed in neurons, and is reduced by acetazolamide and ethoxzolamide, inhibitors of carbonic anhydrase, which catalyses the formation of carbonic acid. On the other hand, these drugs are shown to produce no change of the CO2-HCO3- -induced alkalinization in glial cells. The observations suggest that Na+-HCO3- co-transport across the glial cell membrane, mediating the influx of HCO3- ions into the cell interior, could be responsible for the unusual alkalinization. Further evidence for the activation of Na+-HCO3- co-transport, as a third mechanism involved in pHi homeostasis of the nervous system, is presented.
authors.affiliation: Institut für Zoologie, Lehrstuhl für Neurobiologie, Universität Düsseldorf, Federal Republic of Germany.
authors.forename: W R
authors.initials: WR
authors.lastname: Schlue
authors.forename: J W
authors.initials: JW
authors.lastname: Deitmer
mesh_terms: D000086:Acetazolamide / Q000494:pharmacology; D000584:Amiloride / Q000494:pharmacology; D000643:Ammonium Chloride / Q000378:metabolism; D000818:Animals; D001639:Bicarbonates / Q000494:pharmacology; D002245:Carbon Dioxide / Q000494:pharmacology; D002257:Carbonic Anhydrase Inhibitors / Q000494:pharmacology; D002352:Carrier Proteins / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D027963:Chloride-Bicarbonate Antiporters; D005016:Ethoxzolamide / Q000494:pharmacology; D006706:Homeostasis; D006863:Hydrogen-Ion Concentration; D007865:Leeches / Q000378:metabolism*; D008839:Microelectrodes; D009457:Neuroglia / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D011522:Protons; D012964:Sodium / Q000494:pharmacology; D017923:Sodium-Hydrogen Exchangers; D013267:Stilbenes / Q000494:pharmacology
chemical_list: D001639:Bicarbonates; D002257:Carbonic Anhydrase Inhibitors; D002352:Carrier Proteins; D027963:Chloride-Bicarbonate Antiporters; D011522:Protons; D017923:Sodium-Hydrogen Exchangers; D013267:Stilbenes; D000643:Ammonium Chloride; D002245:Carbon Dioxide; D000584:Amiloride; D012964:Sodium; D000086:Acetazolamide; D005016:Ethoxzolamide