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 language | English (US) |
|---|---|
| Journal | American Journal of Physiology - Renal Physiology |
| Volume | 295 |
| Issue number | 4 |
| DOIs | |
| State | Published - Oct 2008 |
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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 journal › Article
}
TY - JOUR
T1 - Regulation of the epithelial Na+ channel by endothelin-1 in rat collecting duct
AU - Bugaj, Vladislav
AU - Pochynyuk, Oleh
AU - Mironova, Elena
AU - Vandewalle, Alain
AU - Medina, Jorge L.
AU - Stockand, James D
PY - 2008/10
Y1 - 2008/10
N2 - 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.
AB - 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.
KW - Salt-sensitive hypertension
KW - Systemic blood pressure
UR - http://www.scopus.com/inward/record.url?scp=57049119103&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=57049119103&partnerID=8YFLogxK
U2 - 10.1152/ajprenal.90321.2008
DO - 10.1152/ajprenal.90321.2008
M3 - Article
C2 - 18667482
AN - SCOPUS:57049119103
VL - 295
JO - American Journal of Physiology - Renal Physiology
JF - American Journal of Physiology - Renal Physiology
SN - 0363-6127
IS - 4
ER -