K+ depletion increases HCO-3 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 similar to 30-fold in outer medulla, and net HCO(3)(-) flux (J(tCO2)) 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 J(tCO2), whereas 10 mu M Sch-28080 decreased J(tCO2) to 5.1 pmol.min(-1).mm tubule length(-1) (P < 0.001). In KD rats, ouabain 1 mM decreased J(tCO2) to 6.3 pmol.min(-1).mm tubule length(-1) (P < 0.001). Although 10 mu M Sch-28080 also decreased J(tCO2) 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 J(tCO2) in both normal and KD tubules. The data suggest that, in KD, cHKA is induced and mediates increased HCO(3)(-) reabsorption in OMCD, cHKA in vivo is sensitive to both Sch-28080 and ouabain, and cHKA activity is dominant.