The basolateral NHE1 Na+/H+ exchanger regulates transepithelial HCO3- absorption through actin cytoskeleton remodeling in renal thick ascending limb

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Abstract

In the renal medullary thick ascending limb (MTAL), inhibiting the basolateral NHE1 Na+/H+ exchanger with amiloride or nerve growth factor (NGF) results secondarily in inhibition of the apical NHE3 Na +/H+ exchanger, thereby decreasing transepithelial HCO3- absorption. MTALs from rats were studied by in vitro microperfusion to identify the mechanism underlying cross-talk between the two exchangers. The basolateral addition of 10 μM amiloride or 0.7 nM NGF decreased HCO3- absorption by 27-32%. Jasplakinolide, which stabilizes F-actin, or latrunculin B, which disrupts F-actin, decreased basal HCO3- absorption by 30% and prevented the inhibition by amiloride or NGF. Jasplakinolide had no effect on HCO3 - absorption in tubules bathed with amiloride or a Na +-free bath to inhibit NHE1. Jasplakinolide and latrunculin B did not prevent inhibition of HCO3- absorption by vasopressin or stimulation by hyposmolality, factors that regulate HCO3- absorption through primary effects on apical Na+/H+ exchange. Treatment of MTALs with amiloride or NGF for 15 min decreased polymerized actin with no change in total cell actin, as assessed both by fluorescence microscopy and by actin Triton X-100 solubility. Jasplakinolide prevented amiloride-induced actin remodeling. Vasopressin, which inhibits HCO3- absorption by an amount similar to that observed with amiloride and NGF but does not act via NHE1, did not affect cellular F-actin content. These results indicate that basolateral NHE1 regulates apical NHE3 and HCO3- absorption in the MTAL by controlling the organization of the actin cytoskeleton.

Original languageEnglish (US)
Pages (from-to)11439-11447
Number of pages9
JournalJournal of Biological Chemistry
Volume280
Issue number12
DOIs
StatePublished - Mar 25 2005

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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