Premium
The Inhibitory Effect of G β Isoforms on ENaC Activity
Author(s) -
Yu Ling,
Helms My,
AlKhalili Otor,
Yue Qiang,
Eaton Douglas C.
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a536-a
Subject(s) - epithelial sodium channel , heterotrimeric g protein , phospholipase c , gene isoform , reabsorption , chemistry , microbiology and biotechnology , g protein , gq alpha subunit , protein subunit , medicine , endocrinology , signal transduction , biology , kidney , biochemistry , sodium , gene , organic chemistry
Epithelial Na + channel (ENaC) activity, which determines the rate of renal Na + reabsorption, is inhibited by the alpha subunit heterotrimeric G‐protein G αi3 , but the effect of G βγ on ENaC is unclear. Therefore, we tested Gγ 2 combined individually with Gβ 1 through Gβ 5 expressed in A6 cells, and recorded single ENaC activity. Among the five β and γ 2 combinations, the β 1 γ 2 strongly inhibited ENaC activity compared to control cells. In contrast, the other four combinations had no significant effect on ENaC activity. ENaC is activated by phosphatidylinositol (4,5) bisphosphate (PIP 2 ) and G β γ can stimulate phospholipase C (PLC) to reduce PIP 2 . To examine whether the β 1 γ 2 inhibition was due to activation of PLC β , we tested the effect of the PLC inhibitor, U‐73122, and its inactive analog, U‐73343, on ENaC of control and β 1 γ 2 ‐expressing cells. Compared to U73343, U73122 significantly stimulated ENaC activity in β 1γ2 expressing cells; however, there is no difference in control cells. In conclusion, G β1 γ 2 (but not other β isoforms) exerts an inhibitory effect on ENaC activity, and this effect is at least partially due to the activation of PLC. Supported by R37 DK37963.