Fall in intracellular pH mediated by GABAA receptors in cultured rat astrocytes

The influence of muscimol (a specific gamma-aminobutyric acid-A (GABAA) receptor agonist) on intracellular pH (pHi) was studied in cultured rat astrocytes by means of fluorescence spectrophotometry with BCECF as the H+ indicator. In an HCO3(-)-free medium, muscimol had little effect on pHi. In a solution containing 22 mM HCO3-, muscimol produced a reversible, concentration-dependent fall in pHi with a maximum of about 0.1-0.15 units. The muscimol-induced fall in pHi was antagonized by an increase in the external K+ concentration, which suggest that the acidosis is an immediate consequence of a net efflux of HCO3- through GABAA receptor channels rather than an indirect effect caused by a change in membrane potential. The present results raise the possibility that astrocytes may participate in the regulation of extracellular pH at GABAergic synapses and contribute to activity-induced pH changes in nervous tissue.