Modulation of K channels in renal collecting duct
Principal Investigator: WEN-HUI H WANG
Abstract: The main goal of the present proposal is to explore the mechanism by which the proteintyrosine kinase (PTK)-dependent signal transduction pathway mediates the inhibitory effect of a low dietary K+ intake on K+ secretion. Kidney plays a key role in maintaining K+ homeostasis. A high plasma K+ (hyperkalemia) or a low plasma K+ (hypokalemia) could have serious and life threatening consequences. The cortical collecting duct (CCD) is responsible for the final and fine regulation of K+ secretion. K+ secretion is regulated by a variety of factors, such as hormones and K+ diet. The dietary K+ intake is the most important factor which regulates renal K+ secretion: a high K+ intake increases whereas a low K+ intake decreases the renal K+ secretion. The effect of the dietary K+ intake on K+ secretion is partially achieved by changing the number of functional ROMK-like small conductance K+ (SK) channels in the apical membrane of the CCD. It has been demonstrated that a high K+ intake increases whereas a low K+ intake decreases the number of the SK channels in the apical membrane of the CCD. A large body of evidence indicates that PTK plays a key role in mediating the effect of dietary K+ intake on ROMK-like SK channels in the CCD. However, the mechanism by which a low K+ intake increases the PTK expression and PTK activity is not understood. Our preliminary data have strongly suggested that superoxide anions (O2-) and the related product may be responsible for increase in expression of Src-family PTK induced by low dietary K+ intake. In the present proposal, the hypothesis that O2- and the related products are the upstream signals of PTK-dependent pathways responsible for mediating the effect of low K+ intake on ROMK1 will be tested with optical, molecular and electrophysiological approaches.
Funding Period: 1994-01-01 - 2008-12-31
more information: NIH RePORT
- Superoxide anions are involved in mediating the effect of low K intake on c-Src expression and renal K secretion in the cortical collecting ductElisa Babilonia
Department of Pharmacology, New York Medical College, Valhalla, New York 10595, USA
J Biol Chem 280:10790-6. 2005..We conclude that O(2)(-) and related products play a role in mediating the effect of low K intake on c-Src expression and in suppressing ROMK channel activity and renal K secretion...
- Mitogen-activated protein kinases inhibit the ROMK (Kir 1.1)-like small conductance K channels in the cortical collecting ductElisa Babilonia
Department of Pharmacology, New York Medical College, Valhalla, NY 10595, USA
J Am Soc Nephrol 17:2687-96. 2006..It is concluded that low K intake-induced increases in superoxide levels are responsible for stimulation of P38 and ERK and that MAPK inhibit the SK channels by stimulating PTK expression and via a PTK-independent mechanism...
- Angiotensin II inhibits the ROMK-like small conductance K channel in renal cortical collecting duct during dietary potassium restrictionYuan Wei
Department of Pediatrics, Mount Sinai School of Medicine, New York, New York 10029, USA
J Biol Chem 282:6455-62. 2007..We conclude that AngII inhibits ROMK channel activity through PKC-, NADPH oxidase-, and PTK-dependent pathways under conditions of dietary potassium restriction...