EFFECTS OF TEMPERATURE AND INHIBITORS ON HCO3-STIMULATED SWELLING AND ION UPTAKE OF MONKEY CEREBRAL-CORTEX

In the presence of high concentrations of K+, additions of HCO3- as low as 0.35 mM caused a 23% increase in swelling and concomitant increases in the Cl- content of incubating monkey [Macaca mulatta] cerebrocortical slices. The uptake of Cl- was accompanied by increased uptake of Na+ and was highly temperature dependent, showing a marked activation at approximately 30.degree. C. A similar temperature activation was also found for a Mg2+-dependent, HCO3--stimulated ATPase activity in monkey cerebral cortex, consistent with a possible role for this enzyme in the K+ and HCO3--dependent swelling process and its associated ion movements. K+-dependent, HCO3--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 (> 10 .mu.M). A similar biphasic effect on swelling was also seen following addition of ethacrynic acid. Ethacrynic acid at 1-2 mM inhibited HCO3--stimulated ATPase and carbonic anhydrase activity of monkey cerebral cortex, and (Na+ + K+)-ATPase. In the absence of HCO3-, K+-dependent Cl- uptake did not appear to be enzyme-mediated. The K+-dependent, HCO3--stimulated swelling and its associated ion movements may involve several enzyme-mediated processes. The role of astroglia in the regulation of the extracellular ionic milieu in brain under physiological and pathological circumstances is discussed.