Angiotensin II inhibits the ROMK-like small conductance K channel in renal cortical collecting duct during dietary potassium restriction.
Base-line urinary potassium secretion in the distal nephron is mediated by small conductance rat outer medullary K (ROMK)-like channels. We used the patch clamp technique applied to split-open cortical collecting ducts (CCDs) isolated from rats fed a normal potassium (NK) or low potassium (LK) diet to test the hypothesis that AngII directly inhibits ROMK channel activity. We found that AngII inhibited ROMK channel activity in LK but not NK rats in a dose-dependent manner. The AngII-induced reduction in channel activity was mediated by AT1 receptor (AT1R) binding, because pretreatment of CCDs with losartan but not PD123319 AT1 and AT2 receptor antagonists, respectively, blocked the response. Pretreatment of CCDs with U73122 and calphostin C, inhibitors of phospholipase C (PLC) and protein kinase C (PKC), respectively, abolished the AngII-induced decrease in ROMK channel activity, confirming a role of the PLC-PKC pathway in this response. Studies by others suggest that AngII stimulates an Src family protein-tyrosine kinase (PTK) via PKC-NADPH oxidase. PTK has been shown to regulate the ROMK channel. Inhibition of NADPH oxidase with diphenyliodonium abolished the inhibitory effect of AngII or the PKC activator phorbol 12-myristate 13-acetate on ROMK channels. Suppression of PTK by herbimycin A significantly attenuated the inhibitory effect of AngII on ROMK channel activity. We conclude that AngII inhibits ROMK channel activity through PKC-, NADPH oxidase-, and PTK-dependent pathways under conditions of dietary potassium restriction.
Wei
Yuan
Y
Department of Pediatrics, Mount Sinai School of Medicine, New York, New York 10029, USA. yuan.wei@mssm.edu
Zavilowitz
Beth
B
Satlin
Lisa M
LM
Wang
Wen-Hui
WH
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D004032:Diet; D007685:Kidney Tubules, Collecting / Q000737:chemistry / Q000378:metabolism*; D019255:NADPH Oxidases / Q000378:metabolism; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000008:administration & dosage*; D024661:Potassium Channels, Inwardly Rectifying / Q000037:antagonists & inhibitors*; D011493:Protein Kinase C / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism
C510692:Kcnj1 protein, rat; D024661:Potassium Channels, Inwardly Rectifying; D044140:Receptor, Angiotensin, Type 1; D000804:Angiotensin II; D019255:NADPH Oxidases; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C; D011188:Potassium