The relationship between distal tubular proton secretion and dietary potassium depletion: Evidence for up-regulation of H⁺-ATPase

Background. Dietary potassium depletion is associated with elevated plasma bicarbonate concentration and enhanced bicarbonate reabsorption in the distal tubule. The relationship between distal proton secretion and potassium status was investigated by in vivo microperfusion of the superficial distal tubule. Methods. Experiments were performed on anaesthetized rats that had been maintained on either a low-potassium or control diet for 3-5 weeks prior to experimentation. The distal tubules were perfused at 10 nl/min with either a standard or a barium chloride-containing solution, and the late distal tubular transepithelial potential difference (V(te) and pH of the luminal fluid were recorded using a double-barrelled voltage and ion-sensitive microelectrode. Results. In control rats, the V(te) was -40.7 ± 2.4 mV and the tubular fluid pH was 6.44 ± 0.07; in potassium-depleted animals, the V(te) was -15.0 ± 1.4 mV and the pH was 6.76 ± 0.03. The pH values in both groups of animals were significantly lower than would be predicted from the V(te) and systemic pH for passive H⁺ distribution, indicating active proton secretion. Moreover, in hypokalaemic rats, this difference from predicted pH was significantly greater than in control animals (control = 0.27 ± 0.06 vs low-potassium = 0.46 ± 0.03; P < 0.01), suggesting enhanced active proton secretion. During perfusion with a solution containing BaCl₂, the late distal tubule V(te) became lumen positive in potassium-depleted rats, contrasting with an increased lumen negativity in potassium-replete controls. The barium-induced lumen-positive potential difference observed in the hypokalaemic rats was abolished by intravenous administration of acetazolamide. Conclusion. These data are consistent with enhanced electrogenic proton secretion (Ht-ATPase) during dietary potassium deprivation.