Regulation of amiloride-sensitive, na+ channels by endothelin-1 in
distal nephron cells.
Gallego, Manolo S., and Brian N. Ling.
Departments of Medicine and Physiology, Renal Division and The
Center for Cell and Molecular Signaling, Emory University School of
Medicine, and Veterans Affairs Medical Center,, Atlanta, GA 30322
APStracts 3:0059F, 1996.
We used patch clamp methods to investigate the effects of basolateral
ET-1 on the amiloride-sensitive Na+ channel in A6 distal nephron
cells. 100 pM ET-1 decreased channel activity via an increase in mean
time closed (p<0.01; n=10). Channel inhibition by pM ET-1 was
mimicked by an ET-B receptor agonist (p<0.05; n=7) and was
prevented by ET-B antagonists (p=0.14; n=10), but not by an ET-A
antagonist (p<0.05; n=4). With the inhibitory ET-B receptor
blocked, higher doses of ET-1 (10 nM) actually increased channel
activity through an increase in mean time open (p<0.001; n=12).
The current-voltage relationship and the number of channels were not
changed by basolateral ET-1 exposure. We conclude that: 1)
Basolateral ET-1 regulates amiloride-sensitive Na+ channels. 2)
Binding of pM ET-1 to ET-B receptors inhibits, while the binding of
nM ET-1 to a different ET receptor (likely ET-A) stimulates channel
activity. 4) These dose-dependent, distal nephron responses provide a
potential mechanism for the in vivo natriuresis and antinatriuresis
observed in response to _subpressor_ and _pressor_ concentrations of
ET-1, respectively.
Received 10 July 1995; accepted in final form 12 March 1996.
APS Manuscript Number F222-5.
Article publication pending Am. J. Physiol. (Renal Fluid Electrolyte
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 27 March 96