Dietary K⁺ restriction upregulates total and Sch-28080-sensitive bicarbonate absorption in rat tIMCD

In tubules from the terminal segment of the inner medullary collecting duct (tIMCD) from rats with chronic metabolic acidosis, our laboratory has shown that bicarbonate absorption (J_tCO2) is inhibited by removal of K⁺ from the luminal fluid or by the addition of Sch-28080 to the perfusate. The present study asked whether total and/or Sch-28080-sensitiveJ_tCO2 is regulated by changes in systemic K⁺ homeostasis. Rat tIMCD tubules were perfused in vitro in symmetrical,${HCO}_3^{-}$ /CO₂-buffered solutions containing 10 mM KCl + 6 mM NH₄Cl. Total and Sch-28080-sensitiveJ_tCO2 were measured in rats with varying K⁺intake. In K⁺-replete rats, baseline J_tCO2was 2.1 ± 0.3 pmol ⋅ mm⁻¹ ⋅ min⁻¹(n = 6). In rats fed a K⁺-deficient diet for 3 days,J_tCO2 was 5.4 ± 0.7 pmol ⋅ mm⁻¹ ⋅ min⁻¹(n = 16,P < 0.05). To determine the mechanism for the increase in ${HCO}_3^{-}$ absorption observed with K⁺restriction, the Sch-28080-sensitive component ofJ_tCO2 was measured in each treatment group. Following the addition of Sch-28080 (10 μM) to the perfusate, a 40% reduction inJ_tCO2 was observed in K⁺-restricted rats.J_tCO2 was not reduced following the addition of Sch-28080 in rats with normal K⁺ intake. Because Sch-28080-sensitiveJ_tCO2 was increased in K⁺-restricted rats, Sch-28080-sensitiveJ_tCO2 was studied further in tIMCD tubules from rats in this treatment group. In K⁺-restricted rats,J_tCO2 decreased by 20% following the addition of 5 mM ouabain to the perfusate. This ouabain-induced decline inJ_tCO2 was observed both in the presence and in the absence of Sch-28080. We conclude that total and Sch-28080-sensitive net acid secretion is increased with dietary K⁺restriction. However, since ∼50% ofJ_tCO2 is insensitive to both Sch-28080 and ouabain, future studies will be necessary to define other mechanisms of luminal acidification in the rat tIMCD.