Activity-dependent pH shifts in hippocampal slices from normal and carbonic anhydrase II-deficient mice

The type II isoform of carbonic anhydrase is abundant in astrocytes and oligodendroglia. To explore whether the expression of the type II isoform is required for interstitial carbonic anhydrase activity, we studied extracellular pH transients in hippocampal slices from mutant mice devoid of carbonic anhydrase type II and from wild-type littermates. Stimulation of the Schaffer collateral afferents evoked similar extracellular pH transients in the CA1 stratum pyramidale, consisting of a predominant alkaline shift and little or no subsequent acidosis. After 5-s stimulus trains at 10 Hz, alkaline shifts were not significantly different in carbonic anhydrase II-deficient and wild-type preparations, averaging 0.09 +/- 0.04 and 0.08 +/- 0.04 unit pH, respectively. Addition of 1.5 microM benzolamide amplified the alkaline shifts by 385 +/- 146 and 345 +/- 75% in the mutant and wild-type preparations, respectively. Dose response studies with benzolamide displayed similar sensitivity to this carbonic anhydrase inhibitor over a concentration range of 0. 03-10 microM. These data indicate that interstitial carbonic anhydrase activity is effectively unaltered in brains devoid of carbonic anhydrase type II. The results are consistent with the interpretation that a distinct extracellular isoform of carbonic anhydrase exists in brain.