title: Regulation of intra- and extracellular pH in the rat brain in acute hypercapnia: a re-appraisal.
abstract: Recent results have demonstrated that intracellular pH (pHi) in nerve and glial cells is not regulated back to normal during CO2 exposure if extracellular pH (pHe) is reduced. This raises the question about regulation of pHi and pHe in vivo. In order to successively reduce pHe we exposed animals to incremental increases in CO2 tension (11, 27.5, 42.5%) and studied regulation of pHi during the first 90 min of hypercapnia. Extracellular pH, as well as Na+, K+, and Cl- concentrations, were also measured, as were whole tissue contents of Na+, K+, and Cl-. At all CO2 tensions studied, pHe slowly increased during CO2 exposure. In animals breathing 11% CO2 (delta pHe approximately 0.2 units), pHi increased slowly. However, in animals exposed to 27.5% CO2 or 42.5% CO2 (delta pHe > 0.4 units), no regulation of pHi was observed. Extracellular HCO3- concentrations increased substantially already during the first 15 min of hypercapnia (not significant in animals breathing 42.5% CO2), and then gradually rose. These increases were accompanied by a decrease in Cl- and an increase in Na+ concentration, K+ concentration remaining constant. The total tissue content of these ions remained constant, suggesting that extracellular HCO3- concentration increases by Cl-/HCO3- antiport and/or by Na+.2HCO3- symport, the HCO3- emanating from intracellular sources. The results challenge the dogma of the supremacy of mechanisms regulating pHi, and suggest that brain cells, possibly astrocytes, regulate pHe at the expense of their own pH homeostasis. By inference, we further conclude that regulation of pHi normally occurs only if pHe is first regulated back close to normal value.
authors.affiliation: Laboratory for Experimental Brain Research, Experimental Research Center, Lund University Hospital, Sweden.
authors.forename: K
authors.initials: K
authors.lastname: Katsura
authors.forename: T
authors.initials: T
authors.lastname: Kristián
authors.forename: R
authors.initials: R
authors.lastname: Nair
authors.forename: B K
authors.initials: BK
authors.lastname: Siesjö
mesh_terms: D000818:Animals; D001921:Brain / Q000502:physiology*; D004573:Electrolytes / Q000378:metabolism; D005110:Extracellular Space / Q000502:physiology; D006863:Hydrogen-Ion Concentration; D006935:Hypercapnia / Q000378:metabolism*; D007424:Intracellular Fluid / Q000502:physiology; D008297:Male; D051381:Rats
chemical_list: D004573:Electrolytes