Basolateral membrane Na+/H+ exchange enhances HCO-3 absorption in rat medullary thick ascending limb: Evidence for functional coupling between basolateral and apical membrane Na+/H+ exchangers

David W. Good, Thampi George, Bruns A. Watts

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The role of basolateral membrane Na+/H+ exchange in transepithelial HCO-3 absorption (JHCO3) was examined in the isolated, perfused medullary thick ascending limb (MTAL) of the rat. In Na+-free solutions, addition of Na+ to the bath resulted in a rapid, amiloride-sensitive increase in intracellular pH. In MTALs perfused and bathed with solulions containing 146 mM Na+ and 25 mM HCO-3, bath addition of amiloride (1 mM) or 5-(N-ethyl-N-isopropyl) amiloride (EIPA, 50 μM) reversibly inhibited JHCO3 by 50%. Evidence that the inhibition of JHCO3 by bath amiloride was the result of inhibition of Na+/H+ exchange included the following: (i) the IC50 for amiloride was 5-10 μM, (ii) EIPA was a 50-fold more potent inhibitor than amiloride, (iii) the inhibition by bath amiloride was Na+ dependent, and (iv) significant inhibition was observed with EIPA as low as 0.1 μM. Fifty micromolar amiloride or 1 μM EIPA inhibited JHCO3 by 35% when added to the bath but had no effect when added to the tubule lumen, indicating that addition of amiloride to the bath did not directly inhibit apical membrane Na+/H+ exchange. In experiments in which apical Na+/H+ exchange was assessed from the initial rate of cell acidification following luminal EIPA addition, bath EIPA secondarily inhibited apical Na+/H+ exchange activity by 46%. These results demonstrate that basolateral membrane Na+/H+ exchange enhances transepithelial HCO-3 absorption in the MTAL. This effect appears to be the result of cross-talk in which an increase in basolateral membrane Na+/H+ exchange activity secondarily increases apical membrane Na+/H+ exchange activity.

Original languageEnglish (US)
Pages (from-to)12525-12529
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number26
StatePublished - Dec 19 1995


  • Amiloride
  • Cross-talk
  • Intracellular pH
  • Kidney
  • Renal acidification

ASJC Scopus subject areas

  • General


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