pH-sensitive inwardly rectifying chloride current in cultured rat corticalastrocytes

The effect of pH(o) on plasma membrane chloride current of cultured rat cor tical astrocytes was investigated using the whole-cell patch-clamp techniqu e. In the presence of intra- and extracellular solutions with symmetrical h igh Cl- content and K+ channel inhibitors, the cells exhibited an inwardly rectifying current. The current activated slowly at potentials negative to -40 mV and did not display time-dependent inactivation. The current was inh ibited by 0.1 mM cd(2+), 0.1 mM Zn2+, 1 mM 9-anthracene-carboxylic acid, an d 0.2 mM 5-nitro-2-(3-phenylpropylamino)benzoic acid, but not by 10 mM Ba2 or 3 mM Cs+ Reversal potential of the current followed the chloride equili brium potential and was not influenced by changes in K+ or Na+ concentratio n. The inwardly rectifying chloride current was augmented by extracellular acidosis and reduced by alkalosis. The pH sensitivity was most pronounced i n the physiologically relevant pH(o) range of 6.9-7.9. Lowering pH to 6.4 i nduced no additional increase in steady-state current amplitude compared wi th pH(o) 6.9, but it substantially slowed the activation kinetics. Accordin g to its kinetic and pharmacological properties this chloride current is si milar to that found in cultured rat astrocytes after long-term treatment wi th dibutyryl-cAMP, however, in our cultures it was consistently expressed w ithout any treatment with the drug. Considering that astrocytes possess car bonic anhydrase and Cl-/HCO3- antiporter, this current may participate in t he regulation of the interstitial and astrocyte pH. (C) 2001 Wiley-Liss, In c.