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Evidence for modulation of Shaker ‐type (K v 1) channels in rat small cerebral arteries by ancillary K v β 2 subunits
Author(s) -
Joseph Biny K.,
Pesic Miodrag,
Rhee Sung W.,
Rusch Nancy J.
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.21.6.a1158-b
Subject(s) - cerebral arteries , vascular smooth muscle , vasodilation , vasoconstriction , medicine , protein subunit , endocrinology , chemistry , cerebral circulation , biology , anatomy , microbiology and biotechnology , biochemistry , smooth muscle , gene
Voltage‐gated K + (K v ) channels in vascular smooth muscle cells (VSMCs) mediate vasodilation, and their loss is linked to abnormal vascular reactivity. We recently demonstrated that K v channels in rat small cerebral arteries represent pore‐forming K v 1.2/1.5α tetramers, which associate with ancillary K v β 2 subunits. Based on a chaperoning role for K v β 2 in nonvascular tissues, we hypothesized that K v β 2 is required for the normal expression of K v channels in cerebral VSMCs. Cultured rat cerebral VSMCs were electroporated with 10μg of K v β 2 ‐specific siRNA for 48 hours. K v β 2 was knocked down in VSMCs treated with siRNA compared to scrambled sequence. This event was associated with a concomitant decrease in the mature glycosylated K v 1.2α subunits that compose the K v channel tetramers; an increase in immature K v 1.2α was detected. In further studies, we evaluated if the reduced expression of K v channels in abnormally reactive cerebral arteries from hypertensive rats is associated with a loss of K v β 2 subunits. Indeed, cerebral arteries from two different rat models of hypertension showed abnormally low levels of K v β 2 . Collectively, these results suggest that K v β 2 subunits promote anterograde trafficking and expression of K v channels in cerebral VSMCs, and that a loss of K v β 2 is associated with reduced K v channel expression and cerebral vasoconstriction during hypertensive disease. (Supported by HL‐59238‐08).