Regulation of amiloride-sensitive Na+ channels by endothelin-1 in distal nephron cells.
We used patch-clamp methods to investigate the effects of basolateral endothelin-1 (ET-1) on the amiloride-sensitive Na+ channel in A6 distal nephron cells. One hundred picomolar 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 picomolar ET-1 to ET-B receptors inhibits, whereas the binding of nanomolar ET-1 to a different ET receptor (likely ET-A) stimulates, channel activity; and 3) 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.
Gallego
M S
MS
Department of Medicine, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
Ling
B N
BN
D000584:Amiloride / Q000494:pharmacology*; D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000494:pharmacology*; D009399:Nephrons / Q000166:cytology / Q000378:metabolism*; D009994:Osmolar Concentration; D018408:Patch-Clamp Techniques; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin / Q000502:physiology; D026941:Sodium Channel Blockers; D015222:Sodium Channels / Q000187:drug effects*; D014982:Xenopus laevis
D019332:Endothelin-1; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D000584:Amiloride