K+ depletion increases HCO3- reabsorption in OMCD by activation of colonic H(+)-K(+)-ATPase

To probe the role of the isoforms of H(+)-K(+)-ATPase (HKA) in potassium depletion (KD), rats were placed on a KD diet for 2 wk. Colonic HKA (cHKA) mRNA levels increased approximately 30-fold in outer medulla, and net HCO3-flux (JtCO2) in outer medullary collecting duct (OMCD) increased (13.1 pmol.min-1.mm tubule length-1 in control to 17.7 pmol.min-1.mm tubule length-1 in KD; P < 0.01). In normal rats, 1 mM ouabain in perfusate had no effect on JtCO2, whereas 10 microM Sch-28080 decreased JtCO2 to 5.1 pmol.min-1.mm tubule length-1 (P < 0.001). In KD rats, ouabain 1 mM decreased JtCO2 to 6.3 pmol.min-1.mm tubule length-1 (P < 0.001). Although 10 microM Sch-28080 also decreased JtCO2 to 4.6 pmol.min-1.mm tubule length-1 (P < 0.001), the inhibitory effects of Sch-28080 and ouabain were not additive. Removal of K+ from perfusate blocked Sch-28080-sensitive JtCO2 in both normal and KD tubules. The data suggest that, in KD, cHKA is induced and mediates increased HCO3-reabsorption in OMCD, cHKA in vivo is sensitive to both Sch-28080 and ouabain, and cHKA activity is dominant.