FURTHER STUDIES ON THE K+-DEPENDENT SWELLING OF PRIMATE CEREBRAL CORTEX IN VIVO: THE ENZYMATIC BASIS OF THE K+-DEPENDENT TRANSPORT OF CHLORIDE

Abstract— The swelling of intact, exposed primate cerebral cortex perfused in vioo under, isosmotic conditions was a linear function of the concentration of K⁺ in perfusate over the range 25–117 mM. The K⁺-dependent swelling was manifested throughout the depth of the cerebral cortex studied and was associated with an increased content of chloride in the swollen tissue, despite the constancy of the concentration of external chloride. The swelling of the cerebral cortex was a linear function of the temperature of the perfusate over the range 15–38°C, despite the constancy of the concentration of external K⁺. Moreover, the content of chloride in the swollen cerebral cortex was a linear function of the temperature of the overlying perfusate, despite the constancy of the external concentration of chloride. The changes in the contents of Na⁺ and K⁺ in the swollen cerebral cortex perfused with solutions containing constant concentrations of external Na⁺ and K⁺ but differing in temperature suggested that the fluid of swelling in the tissue was rich in both K⁺ and CI^-, as had been shown previously in vitro. Perfusion of the exposed, intact cerebral cortex in uiuo with K⁺-rich fluids usually involved the reciprocal reduction of the concentrations of Na+ in the perfusate to maintain isotonicity. When comparable reductions in the concentration of external Na⁺ were achieved by replacement with choline (instead of K⁺), swelling of the perfused, exposed cortex was significantly less than that attributed to isotonic, K⁺-rich but Na⁺-poor fluids. These observations suggested that it was the elevated levels of K⁺ rather than lowered concentrations of Na+ that promoted the swelling of the perfused cerebral cortex. The apparent rate of influx of ³⁶Cl from the perfusate into the underlying exposed and intact monkey cerebral cortex in vivo was a linear function of the concentration of K⁺ in perfusate over the range 25–117 mM and conformed to Michaelis-Menten kinetics when plotted according to Lineweaver and Burk. Moreover, the apparent influx of chloride from perfusate into swollen cerebral cortex was a linear function of the percentage swelling of cerebral cortex over the range 6–30 per cent. However, the apparent rate of influx of chloride from perfusate into unswollen cortex was not consistent with the linear correlation already described for swollen cerebral cortex. One reason for this discrepancy was the reduction in the size of the true (inulin) extracellular space associated with the K⁺-dependent swelling of cerebral cortex in vivo. The anatomical locus for this K⁺-dependent swelling of cerebral cortex was an expanded glial compartment, as demonstrated by electron-microscopy. The parenteral administration (50 mg/kg) or local perfusion (5 mM) of acetazolamide inhibited the K⁺-dependent swelling of cerebral cortex in vivo. Moreover, administration of acetazolamide inhibited the K⁺-dependent increase in content of C1- and the K⁺-dependent rate of influx of ³⁶Cl into swollen cerebral cortex. We have discussed the possible enzymatic basis of these K⁺-dependent alterations in content of fluid and chloride and transport of chloride in mammalian cerebral cortex in viuo.