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- Title
Acute regulation of the epithelial Na<sup>+</sup> channel (ENaC) by phosphatidylinositol 3-kinase in isolated collecting duct principal cells.
- Authors
Staruschenko, Alexander; Pochynyuk, Oleh; Bugaj, Vladislav; Vandewalle, Alain; Stockand, James D.
- Abstract
ENaC activity is rate limiting for Na+ reabsorption across the distal nephron. ENaC is a target for PI3-K and its down-stream phospholipid-dependent kinase effectors, including Sgk. Emerging evidence suggests that there is close coupling between PI3-K and ENaC with the kinase also influencing channel gating independent of Sgk. To further study acute regulation of ENaC by PI3-K, we isolated cortical collecting ducts (CCD) from rats maintained on a low sodium diet and used patch-clamp electrophysiology to assess the single channel properties of ENaC. Inhibition of PI3-K with either wortmannin or LY294002, but not the inactive analogue LY303511, rapidly decreased ENaC open probability and activity. These compounds elicited an identical response in the cortical collecting duct cell line, MPKCCD14. IGF-I increased Na+ reabsorption across MPKCCD14 cells via PI3-K with LY294002 completely abolishing IGF-I actions on transport. In contrast, MAPK and ROCK inhibitors PD98059 and H1152, respectively, had no effect on IGF-I induced Na+ transport. However, the PTEN inhibitor bpV (pic) lessened inhibition of Na+ transport by LY294002 stressing the importance of the equilibrium between production and degradation of PIP3. These results are the first to demonstrate in a native preparation that PI3-K acutely influences ENaC gating likely through a mechanism independent of Sgk.
- Subjects
SODIUM channels; PHOSPHOINOSITIDES; KIDNEY tubules; PHOSPHOLIPIDS; PATCH-clamp techniques (Electrophysiology); SALT-free diet; CELL lines; LABORATORY rats
- Publication
FASEB Journal, 2007, Vol 21, Issue 6, pA954
- ISSN
0892-6638
- Publication type
Article
- DOI
10.1096/fasebj.21.6.a954