Cr. Rose et Br. Ransom, MECHANISMS OF H-ASPARTATE IN RAT HIPPOCAMPAL ASTROCYTES( AND NA+ CHANGES INDUCED BY GLUTAMATE, KAINATE, AND D), The Journal of neuroscience, 16(17), 1996, pp. 5393-5404
The excitatory transmitter glutamate (Glu), and its analogs kainate (K
A), and D-aspartate (D-Asp) produce significant pH changes in glial ce
lls. Transmitter-induced pH changes in glial cells, generating changes
in extracellular pH, may represent a special form of neuronal-glial i
nteraction. We investigated the mechanisms underlying these changes in
intracellular H+ concentration ([H+](i)) in cultured rat hippocampal
astrocytes and studied their correlation with increases in intracellul
ar Na+ concentration ([Na+](i)), using fluorescence ratio imaging with
2',7'-bis(carboxyethyl)-5,6-carboxyfluorescein (BCECF) or sodium-bind
ing benzofuran isophthalate (SBFI). Glu, KA, or D-Asp evoked increases
in [Na+](i); Glu or D-Asp produced parallel acidifications. KA, in co
ntrast, evoked biphasic changes in [H+](i), alkaline followed by acid
shifts, which were unaltered after Ca2+ removal and persisted in O Cl-
-saline, but were greatly reduced in CO2/HCO3--free or Na+-free saline
, or during 4,4'-diisothiocyanato-stilbene-2,2-'disulphonic acid (DIDS
) application. The non-NMDA receptor antagonist 6-cyano-7-nitroquinoxa
line-2,3-dione (CNQX) blocked KA-evoked changes in [H+](i) and [Na+](i
), indicating that they were receptor-ionophore mediated. In contrast,
CNQX increased the [H+](i) change and decreased the [Na+](i) change i
nduced by Glu. D-Asp, which is transported but does not act at Glu rec
eptors, induced [H+](i) and [Na+](i) changes that were virtually unalt
ered by CNQX. Our study indicates that [Na+](i) increases are not prim
arily responsible for Glu- or KA-induced acidifications in astrocytes.
Instead, intracellular acidifications evoked by Glu or D-Asp are main
ly caused by transmembrane movement of acid equivalents associated wit
h Glu/Asp-uptake into astrocytes. KA-evoked biphasic [H+](i) changes,
in contrast, are probably attributable to transmembrane ion movements
mediated by inward, followed by outward, electrogenic Na+/HCO3- cotran
sport, reflecting KA-induced biphasic membrane potential changes.