Evidence for involvement of protein kinase C in regulation of intracellular pH by Cl-/HCO-3 antiport.

The activity of the main base-extruding mechanism in Vero cells, the Na(+)-independent Cl-/HCO-3 antiport, increases 5- to 10-fold when the cytosolic pH (pHi) is increased over a narrow range close to neutrality. We have studied the effect on this regulation of stimulation and inhibition of protein kinase C by short-term and long-term treatment with the phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA). After short-term treatment with TPA to stimulate the kinase, the threshold value for activation of the antiport is shifted to a more acidic pH. After prolonged treatment with TPA to downregulate protein kinase C the sensitivity of the antiport to variation in proton concentration was lowered, possibly by reducing the number of essential proton-binding sites. Concomitantly, the steady state pHi of the cells was increased. The data indicate that protein kinase C is involved in the regulation of the Na(+)-independent Cl-/HCO-3 antiport.