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PSD 95 scaffolds associated with vascular K V 1 channels are post‐transcriptionally down‐regulated in cerebral arteries during hypertension
Author(s) -
Joseph Biny K,
Rusch Nancy J,
Rhee Sung W
Publication year - 2010
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.24.1_supplement.576.3
Subject(s) - pdz domain , cerebral arteries , scaffold protein , blot , medicine , vasodilation , endocrinology , chemistry , immunoprecipitation , biology , anatomy , microbiology and biotechnology , signal transduction , biochemistry , gene
Recently we reported that a transcriptional down‐regulation of pore‐forming α‐subunits of the Shaker ‐type voltage‐gated K + (K V 1) channels may contribute to a vasodilator defect in cerebral arteries of hypertensive rats. The presence of a class 1 PDZ binding motif in the C‐terminus of the α‐subunits (α1.2 and α1.5) of K V 1 channels raises the possibility that these subunits bind to PDZ domains of the molecular scaffold PSD 95 ( P ost S ynaptic D ensity 95). The current study examined the possibility that a loss of K V 1 channels may directly mediate the down‐regulation of PSD 95 scaffolds in rat cerebral arteries. First, reciprocal co‐immunoprecipitation studies revealed that α1.2 associates with PSD 95. Second, Western blotting and real‐time PCR analysis indicated a post‐transcriptional down‐regulation of PSD 95 in cerebral arteries of genetically hypertensive rats and aortic‐banded rats compared to normotensive controls. Third, α1.2 and/or α1.5 siRNAs reduced the expression levels of the pore‐forming α1.2 and α1.5 subunits and concomitantly reduced PSD 95 in rat cerebral arteries in short‐term culture. Taken together, our results suggest a previously uncharacterized function for vascular K V 1 channels. We propose that they directly regulate the expression of the PSD 95 scaffolding protein in rat cerebral arteries.