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 Citations (Scopus)

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)
JournalAmerican Journal of Physiology - Renal Physiology
Volume295
Issue number4
DOIs
StatePublished - Oct 2008

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Epithelial Sodium Channels
Endothelin-1
src-Family Kinases
Natriuresis
Electrophysiology
Endothelins
Type C Phospholipases
Protein Kinase C
Salts
Hypertension
Kidney
Membranes

Keywords

  • Salt-sensitive hypertension
  • Systemic blood pressure

ASJC Scopus subject areas

  • Physiology
  • Urology

Cite this

Regulation of the epithelial Na+ channel by endothelin-1 in rat collecting duct. / Bugaj, Vladislav; Pochynyuk, Oleh; Mironova, Elena; Vandewalle, Alain; Medina, Jorge L.; Stockand, James D.

In: American Journal of Physiology - Renal Physiology, Vol. 295, No. 4, 10.2008.

Research output: Contribution to journalArticle

Bugaj, Vladislav ; Pochynyuk, Oleh ; Mironova, Elena ; Vandewalle, Alain ; Medina, Jorge L. ; Stockand, James D. / Regulation of the epithelial Na+ channel by endothelin-1 in rat collecting duct. In: American Journal of Physiology - Renal Physiology. 2008 ; Vol. 295, No. 4.
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