Regulation of the epithelial Na+ channel by endothelin-1 in rat collecting duct

Vladislav Bugaj, Oleh Pochynyuk, Elena Mironova, Alain Vandewalle, Jorge L. Medina, James D. Stockand

Research output: Contribution to journalArticle

75 Scopus citations

Abstract

We used patch-clamp electrophysiology to investigate regulation of the epithelial Na+ channel (ENaC) by endothelin-1 (ET-1) in isolated, split-open rat collecting ducts. ET-1 significantly decreases ENaC open probability by about threefold within 5 min. ET-1 decreases ENaC activity through basolateral membrane ETB but not ETA receptors. In rat collecting duct, we find no role for phospholipase C or protein kinase C in the rapid response of ENaC to ET-1. ET-1, although, does activate src family tyrosine kinases and their downstream MAPK1/2 effector cascade in renal principal cells. Both src kinases and MAPK1/2 signaling are necessary for ET-1-dependent decreases in ENaC open probability in the split-open collecting duct. We conclude that ET-1 in a physiologically relevant manner rapidly suppresses ENaC activity in native, mammalian principal cells. These findings may provide a potential mechanism for the natriuresis observed in vivo in response to ET-1, as well as a potential cause for the salt-sensitive hypertension found in animals with impaired endothelin signaling.

Original languageEnglish (US)
Pages (from-to)F1063-F1070
JournalAmerican Journal of Physiology - Renal Physiology
Volume295
Issue number4
DOIs
StatePublished - Oct 1 2008

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Keywords

  • Salt-sensitive hypertension
  • Systemic blood pressure

ASJC Scopus subject areas

  • Physiology
  • Urology

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