Regulation of the epithelial Na+ channel by endothelin-1 in rat collecting duct.
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.
Bugaj
Vladislav
V
Department of Physiology 7756, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA.
Pochynyuk
Oleh
O
Mironova
Elena
E
Vandewalle
Alain
A
Medina
Jorge L
JL
Stockand
James D
JD
D000818:Animals; D002461:Cell Line, Transformed; D019332:Endothelin-1 / Q000378:metabolism* / Q000494:pharmacology; D053503:Epithelial Sodium Channels / Q000502:physiology*; D005260:Female; D006977:Hypertension, Renal / Q000378:metabolism / Q000503:physiopathology; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology*; D007685:Kidney Tubules, Collecting / Q000166:cytology / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D008297:Male; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D044022:Receptor, Endothelin A / Q000378:metabolism; D044023:Receptor, Endothelin B / Q000378:metabolism; D019061:src-Family Kinases / Q000378:metabolism
D019332:Endothelin-1; D053503:Epithelial Sodium Channels; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D019061:src-Family Kinases; D019950:Mitogen-Activated Protein Kinase 1