REGULATION OF INTRACELLULAR AND EXTRACELLULAR PH IN THE RAT-BRAIN IN ACUTE HYPERCAPNIA - A REAPPRAISAL

Recent results have demonstrated that intracellular pH (pH(i)) in nerv e and glial cells is not regulated back to normal during CO2 exposure if extracellular pH (pH(e)) is reduced. This raises the question about regulation of pH(i) and pH(e) in vivo. In order to successively reduc e pH(e) we exposed animals to incremental increases in CO2 tension (11 , 27.5, 42.5%) and studied regulation of pH(i) during the first 90 min of hypercapnia. Extracellular pH, as well as Na+, K+, and C1(-) conce ntrations, were also measured, as were whole tissue contents of Na+, K +, and C1(-). At all CO2 tensions studied, pH(e) slowly increased duri ng CO2 exposure. In animals breathing 11% CO2 (Delta pH(e) similar to 0.2 units), pH(i) increased slowly. However, in animals exposed to 27. 5% CO2 or 42.5% CO2 (Delta pH(e) > 0.4 units), no regulation of pH(i) was observed. Extracellular HCO3- concentrations increased substantial ly already during the first 15 min of hypercapnia (not significant in animals breathing 42.5% CO2), and then gradually rose. These increases were accompanied by a decrease in C1(-) and an increase in Na+ concen tration, K+ concentration remaining constant. The total tissue content of these ions remained constant, suggesting that extracellular HCO; c oncentration increases by Cl-/HCO3- antiport and/or by Na+ 2HCO(3)(-) symport, the HCO3- emanating from intracellular sources. The results c hallenge the dogma of the supremacy of mechanisms regulating pH(i), an d suggest that brain cells, possibly astrocytes, regulate pH(e) at the expense of their own pH homeostasis. By inference, we further conclud e that regulation of pH(i) normally occurs only if pH(e) is first regu lated back close to normal value.