The effects of temperature and inhibitors on HCO 3−- stimulated swelling and ion uptake of monkey cerebral cortex

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In the presence of high concentrations of K +, additions of HCO 3− as low as0.35m M caused a 23% increase in swelling, and concomitant increases in the chloride content of incubating monkey cerebrocortical slices. The uptake of chloride was accompanied by increased uptake of sodium and was highly temperature dependent, showing a marked activation at approximately 30°C. A similar temperature activation was also found for a Mg 2+-dependent, HCO 3−-stimulated ATPase activity in monkey cerebral cortex, consistent with a possible role for this enzyme in the K + and HCO 3−-dependent swelling process and its associated ion movements. K +-dependent, HCO 3−-stimulated cerebrocortical tissue swelling with uptake of Na + and Cl − was inhibited by acetazolamide indicating that carbonic anhydrase was also involved. The addition of ouabain also inhibited swelling and K + and Cl − uptake at low concentrations, but led to increased swelling at higher concentrations (10μ M). A similar biphasic effect on swelling was also seen following addition of ethacrynic acid. Ethacrynic acid at1–2m M was found to inhibit HCO 3 −-stimulated ATPase and carbonic anhydrase activity of monkey cerebral cortex, as well as (Na ++K +)-ATPase. In the absence of HCO 3−, K +-dependent Cl − uptake did not appear to be enzyme-mediated. These results suggest that gthe K +-dependent, HCO 3−-stimulated swelling and its associated ion movements may involve several enzyme-mediated processes. The significance of these findings is discussed in terms of the role of astroglia in the regulation of the extracellular ionic milieu in brain under physiological and pathological circumstances.