Extracellular pH modifies adaptive response to high K+ in cultured canine kidney cells

The chronic interactive and independent effects of extracellular pH and K+ on renal Na(+)-K(+)-adenosinetriphosphatase (ATPase) activity and active K+ transport were studied in the Madin-Darby canine kidney (MDCK) cell line. Confluent cell monolayers were incubated for 24 h in control (4 mM) or high (7.5 mM) K+ medium at acid (6.8) or neutral (7.4) pH. Under acid pH conditions, exposure to high K+ elicited a rise of 133% in maximum Na(+)-K(+)-ATPase activity and 66% in active K+ uptake. In contrast, high K+ had no effect on enzyme activity or K+ uptake at neutral pH. Detergent-activated Na(+)-K(+)-ATPase assay demonstrated a latent pool of enzyme at acid pH-control K+, which seemed to account entirely for the increase in Na(+)-K(+)-ATPase activity after exposure to high K+. The effects of pH appeared unrelated to HCO3- and Cl- concentration in the extracellular environment. We conclude that the upregulatory effect of high K+ on renal Na(+)-K(+)-ATPase is pH dependent. The data suggest that a pool of catalytically inactive enzyme exists only at acid extracellular pH at K+ concentrations in the normal physiological range and that K+ adaptation, at least initially, is the result of recruitment of this latent intracellular pool. In the intact cell extracellular K+ and luminal pH may interact to modify catalytic turnover rate as well as bioavailability of Na(+)-K(+)-ATPase.