An apical K+-dependent HC03- transport pathway opposes transepithelial HC03- absorption in rat medullary thick ascending limb

Bruns A. Watts, David W. Good

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Absorption of HCO3- in the medullary thick ascending limb (MTAL) is mediated by apical membrane Na+/H+ exchange. The identity and function of other apical acid-base transporters in this segment have not been defined. The present study was designed to examine apical membrane HCO3-/OH-/H+ transport pathways in the rat MTAL and to determine their role in transepithelial HCO3- absorption. MTALs were perfused in vitro in Na+- and Cl--free solutions containing 25 mM HCO3-, 5% CO2. Lumen addition of either 120 mM Cl- or 50 mM Na+ (50 μM EIPA present) had no effect on intracellular pH (pHi). Lumen Cl- addition also had no effect on pHi in the presence of 145 mM Na+ or in the nominal absence of HCO3-/CO2. Thus there was no evidence for apical Cl-/HCO3- (OH-) exchange, Na+-dependent Cl-/HCO3- exchange, or Na+-HCO3- cotransport. In contrast, in tubules studied in Na+- and Cl--free solutions containing 25 mM HCO3-, 5% CO2 and 120 mM K+, removal of luminal K+ induced a rapid and pronounced decrease in pHi (ΔpHi = 0.56 ± 0.06 pH U). pHi recovered following lumen K+ readdition. The initial rate of net base efflux induced by lumen K+ removal was decreased 85% at the same pHi in the nominal absence of HCO3 -/CO2, indicating a dependence on HCO3 -/CO2 and arguing against apical K+/H + exchange. A combination of the apical K+ channel blockers quinidine (0.1 mM) and glybenclamide (0.25 mM) had no effect on the lumen K+-induced pHi changes, arguing against electrically coupled K+ and HCO3- conductances. The effect of lumen K+ on pHi was inhibited by 1 mM H 2DIDS. In addition, lumen addition of DIDS increased transepithelial HCO3- absorption from 10.7 ± 0.7 to 14.9 ± 0.7 pmol·min-1·mm-1 (P < 0.001) and increased pHi slightly in MTAL studied in physiological solutions (25 mM HCO3- and 4 mM K+). Lumen DIDS stimulated HCO3- absorption in the absence and presence of furosemide. These results are consistent with an apical membrane K +-dependent HCO3- transport pathway that mediates coupled transfer of K+ and HCO3- from cell to lumen in the MTAL. This mechanism, possibly an apical K +-HCO3- cotransporter, functions in parallel with apical Na+/H+ exchange and opposes transepithelial HCO3- absorption.

Original languageEnglish (US)
Pages (from-to)F57-F63
JournalAmerican Journal of Physiology - Renal Physiology
Volume287
Issue number1 56-1
DOIs
StatePublished - Jul 1 2004

Keywords

  • Acid-base transport
  • Cl/HCO exchange
  • K-HCOcotransport
  • KCC
  • Na/H exchange

ASJC Scopus subject areas

  • Physiology
  • Urology

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