Expression of rat thick limb Na/H exchangers in potassium depletion and chronic metabolic acidosis.

Regulation of renal transporter expression has been shown to support adaptation of transporter activities in several chronic situations. Basolateral and apical Na/H exchangers (NHE) in medullary thick ascending limb (MTAL) are involved in NH₄⁺ and HCO₃⁺ absorption, respectively. The NH₄⁺ absorption rate in Henle's loop is increased in chronic metabolic acidosis (CMA) and potassium depletion (KD), which may be secondary to the increased NH₄⁺ concentration in luminal fluid and/or to an increased NH₄⁺ absorptive capacity of MTAL. HCO₃^- absorptive capacity in Henle's loop is increased in CMA and decreased in metabolic alkalosis, but is unchanged in KD despite the presence of metabolic alkalosis. The present study compared the effects of NH₄Cl-induced CMA and KD on the expression of basolateral NHE-1 and the effect of KD on the expression of apical NHE-3 in MTAL.

NHE-1 and NHE-3 mRNAs and proteins were assessed by a competitive reverse transcription-polymerase chain reaction (RT-PCR) method and semiquantitative immunoblots, respectively, in MTAL-purified suspensions from rats with CMA and KD.

NHE-1 protein abundance was similarly increased (∼90%) at two and five weeks of KD, while NHE-1 mRNA amount in MTAL cells was increased at two weeks of KD and returned to normal values by five weeks of KD. In contrast, NHE-1 mRNA and protein abundance did not change in CMA. NHE-3 protein abundance remained unchanged in both two and five weeks of KD, while NHE-3 mRNA was unchanged by two weeks of KD and reduced by ∼50% at five weeks of KD.

The results suggest the following: (1) in KD, where the increased NH₄⁺ concentration of luminal fluid that favors NH₄⁺ absorption is counterbalanced by a decrease in BSC1 expression and activity, the increased NHE-1 expression may support an increased MTAL NH₄⁺ absorptive capacity in CMA, NHE-1 expression is not specifically regulated and remains unchanged, suggesting that the increase in NH₄⁺ concentration in luminal fluid is the main determinant of increased NH₄⁺ absorption in MTAL. (2) In KD, NHE-3 expression did not decrease despite the presence of metabolic alkalosis, in agreement with the unchanged HCO₃^- absorptive capacity of Henle's loop.