PROTEIN-KINASE-C IN INTRACELLULAR PH REGULATION IN ALVEOLAR TYPE-II CELLS

The Na+/H+ exchanger and Na+-HCO3- cotransporter have been implicated in regulation of intracellular pH (pH(i)) in alveolar type II cells. T his study demonstrates that activation of protein kinase C (PKC) stimu lates both of these ion transporters in type II cells. Treatment of ty pe II cells with 80 nM phorbol 12-myristate 13-acetate (PMA) increased the resting pH(i) in a time-dependent manner Compared with control ce lls, the rates of recovery from an acid load increased with PMA treatm ent, reaching a maximum at 15 min, and returned to control levels by 3 h. The PMA-stimulated changes in recovery rate were sensitive to H-7, a PKC inhibitor For PMA treatment up to 2 h, these recoveries were al so sensitive to dimethylamiloride (DMA), an inhibitor of Na+/H+ exchan ger activity, and to HCO3-, suggesting activation of both the Na+/H+ e xchanger and the Na+-HCO3-, cotransporter. After prolonged (3 h) treat ment with PMA, however, the recovery was insensitive to DMA but was se nsitive to HCO3-, suggesting that the Na+/H+ exchanger was no longer a ctive and that most of the recovery was mediated by the Na+-HCO3- cotr ansporter PMA treatment also altered the Na+ kinetics of the recovery from an acid load with respect to the Michaelis constant (K-m) and max imal ion flux (V-max), suggesting protein modifications of each transp orter. We suggest that PKC activation in type II cells results in acut e and long-term changes in pH(i) regulatory mechanisms mediated by the Na+/H+ exchanger and by the Na+-HCO3- cotransporter.