Functional adaptation to high PCO2 of apically and basolaterally located Na+/H+ exchange activities in cultured renal cell lines.

Cultured renal epithelial cells grown on filter support were examined for functional adaptation of Na+/H+ exchange activities to "respiratory" acidaemia, which was mimicked by increasing PCO2 from 5% to 10% during 24 h or 48 h of cell culture. We have selected proximal tubular cell lines with either dual location of Na+/H+ exchange activities (MCT cells, RKPC-2 cells), apical location of Na+/H+ exchange activity (OK/WOK cells) or a basolateral location of Na+/H+ exchange activities (LLC-PK1/clone 4 cells, MDCK cells). Na+/H+ exchange activity was determined microspectrofluorometrically (using BCECF) in the absence of CO2/HCO3-. Respiratory acidaemia specifically increased apical Na+/H+ exchange activity (previously classified as amiloride-resistant) in MCT cells, in RKPC-2 cells and in WOK cells; it stimulated basolateral Na+/H+ exchange activity (previously shown to be amiloride-sensitive) in RKPC-2 cells, in LLC-PK1/clone 4 cells and in MDCK cells, but did not affect basolateral Na+/H+ exchange activity in MCT cells. In MCT and in RKPC-2 cells the effect of high PCO2 on apical Na+/H+ exchange was prevented by inhibition of protein kinase C. In RKPC-2 cells, activation of basolateral Na+/H+ exchange by high PCO2 occurred also when protein kinase C was inhibited. In conclusion, these studies demonstrate stimulation of apical Na+/H+ exchange, but differential regulation of basolateral Na+/H+ exchange activities in response to a high-PCO2-induced acid environment. Protein kinase C activation might be involved in mediating the effect of acidaemia on stimulation of apical Na+/H+ exchange activity (MCT and RKPC-2 cells).