Transepithelial HCO3- absorption is defective in renal thick ascending limbs from Na+/H+ exchanger NHE1 null mutant mice

David W. Good, Bruns A. Watts, Thampi George, Jamie W. Meyer, Gary E. Shull

Research output: Contribution to journalArticle

38 Scopus citations

Abstract

In the medullary thick ascending limb (MTAL) of rat kidney, inhibiting basolateral Na+/H+ exchange with either amiloride or nerve growth factor (NGF) results secondarily in inhibition of apical Na +/H+ exchange, thereby decreasing transepithelial HCO 3- absorption. To assess the possible role of the Na +/H+ exchanger NHE1 in this regulatory process, MTALs from wild-type and NHE1 knockout (NHE1-/-) mice were studied using in vitro microperfusion. The rate of HCO3- absorption was decreased 60% in NHE1-/- MTALs (15.4 ± 0.5 pmol·min-1·mm-1 wild-type vs. 6.0 ± 0.5 pmol·min-1·mm-1 NHE1-/-). Transepithelial voltage, an index of the NaCl absorption rate, did not differ in wild-type and NHE1-/- MTALs. Basolateral addition of 10 μM amiloride or 0.7 nM NGF decreased HCO3- absorption by 45-49% in wild-type MTALs but had no effect on HCO3- absorption in NHE1-/- MTALs. Inhibition of HCO3 - absorption by vasopressin and stimulation by hyposmolality, both of which regulate MTAL HCO3- absorption through primary effects on apical Na+/H+ exchange, were similar in wild-type and NHE1-/- MTALs. Thus the regulatory defect in NHE1 -/- MTALs is specific for factors (bath amiloride and NGF) shown previously to inhibit HCO3- absorption through primary effects on basolateral Na+/H+ exchange. These findings demonstrate a novel role for NHE1 in transepithelial HCO3- absorption in the MTAL, in which basolateral NHE1 controls the activity of apical NHE3. Paradoxically, a reduction in NHE1-mediated H+ extrusion across the basolateral membrane leads to a decrease in apical Na +/H+ exchange activity that reduces HCO3 - absorption.

Original languageEnglish (US)
Pages (from-to)F1244-F1249
JournalAmerican Journal of Physiology - Renal Physiology
Volume287
Issue number6 56-6
DOIs
StatePublished - Dec 1 2004

    Fingerprint

Keywords

  • Growth factors
  • Sodium hydrogen exchanger type 3

ASJC Scopus subject areas

  • Physiology
  • Urology

Cite this