K depletion stimulates in vivo HCO3reabsorption in surviving rat distal tubules

To evaluate whether K depletion enhances in vivo bicarbonate reabsorption (JtCO2)in surviving distal tubules (DT), we compared DTJtCO2in five-sixths nephrectomized rats (Nx) with and without dietary K depletion (Nx-K). Furthermore, to identify possible mechanisms of increasedJtCO2, we perfused inhibitors of proton secretion in both Nx and Nx-K rats.JtCO2(102 ± 8 pmol ⋅ min−1⋅ mm−1) was significantly increased in Nx-K vs. Nx rats (65 ± 7 pmol ⋅ min−1⋅ mm−1,P< 0.05) but unaffected by 10−6M losartan perfusion (94 ± 6 pmol ⋅ min−1⋅ mm−1,P= not significant). Although 10−5M Sch-28080 also had no significant effect, 5 × 10−9M concanamycin A perfusion significantly decreasedJtCO2in Nx-K rats to 65 ± 8 pmol ⋅ min−1⋅ mm−1(P< 0.05). Morphometric evaluation and H+-ATPase immunogold labeling of Nx-K A-type intercalated cells revealed cellular hypertrophy, elaborated apical microplicae, and enhanced H+-ATPase apical polarization. Accordingly, these combined studies confirm that K depletion enhancesJtCO2in surviving DT by stimulating H+-ATPase activity, independent of the AT1receptor.