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Downregulation of mechanosensitive βENaC and γENaC in VSMCs in ASIC2 +/− mice
Author(s) -
Gan Kim P,
VanLandingham Lauren G,
Drummond Heather A
Publication year - 2008
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.22.1_supplement.1151.7
Subject(s) - epithelial sodium channel , mechanosensitive channels , downregulation and upregulation , chemistry , medicine , endocrinology , microbiology and biotechnology , biology , ion channel , receptor , sodium , biochemistry , gene , organic chemistry
Previously, we evaluated the importance of the mechanosensitive protein ASIC2 in pressure‐induced constriction (PIC) in middle cerebral arteries in the ASIC2 mouse model. ASIC2 +/+ and −/− mice developed similar PIC (16 ± 2 and 10 ± 3%, respectively at 90 mm Hg). However, surprisingly, ASIC2 +/− mice developed less PIC (4 ± 2%). Since previous reports indicate 1) β and γENaC also mediate PIC and 2) ENaC can interact with ASIC2, the goal of our study was to determine if reductions in mechanosensitive γ and γENaC protein might contribute to loss of PIC in ASIC2 +/− mice. To address this, we used quantitative immunolabeling for ASIC2, βENaC and γENaC in VSMCs from ASIC2 +/+, +/− and −/− mice. Fluorescence intensity (FI) was normalized for α‐actin and background subtracted (Fig. 1). We found β and γENaC were suppressed in +/−, and γENaC upregulated in −/− mice VSMCs, suggesting an interaction between βENaC, γENaC and ASIC2. Next, we used co‐immunoprecipitation and confirmed a biochemical interaction among βENaC, γENaC and ASIC2 in isolated vessels. These findings suggest the loss of PIC in ASIC2 +/− mice may also be dependent on inhibition of VSMC β and γENaC expression and recovery of PIC in ASIC2 −/− mice may be due to compensatory upregulation of γENaC. Our findings support the hypothesis that mechanosensitive ion channels initiating pressure‐induced constriction in VSMCs include βENaC, γENaC and ASIC2. Supported by AHA and NHLBI.