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Postsynaptic density 95 (PSD95) scaffolding of Shaker ‐type potassium channels in smooth muscle cells regulates the diameter of rat cerebral arteries
Author(s) -
Joseph Biny K,
Pathan Asif R,
Thakali Keshari M,
Kang Eunju,
Parelkar Nikhil K,
Rusch Nancy J,
Rhee Sung W
Publication year - 2011
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.25.1_supplement.1081.9
Subject(s) - postsynaptic density , postsynaptic potential , cerebral arteries , scaffold protein , potassium channel , microbiology and biotechnology , vascular smooth muscle , ion channel , biophysics , biology , medicine , endocrinology , signal transduction , receptor , biochemistry , smooth muscle
Postsynaptic density 95 (PSD95) is a 95 kDa scaffolding protein in the brain that clusters postsynaptic proteins including ion channels, receptors and other signaling partners. Voltage‐gated, Shaker ‐type, K + (K V 1) channels are key binding partners of PSD95 scaffolds in postsynaptic neurons. K V 1 channels are also found in cerebral vascular smooth muscle cells (cVSMCs) and mediate hyperpolarization and vasodilation of cerebral arteries. This study was designed to determine if PSD95 scaffolds K V 1 channels in cVSMCs to promote vasodilation of cerebral arteries. PSD95 mRNA and protein was detected in cVSMCs by real‐time PCR and Western blotting. Furthermore, PSD95 co‐immunoprecipitated with the pore‐forming α1.2 subunit of the K V 1 channel. Antisense‐mediated knockdown of PSD95 in rat cerebral arteries profoundly reduced K V 1 channel expression and patch‐clamped cVSMCs exhibited a loss of K V 1 current. Loss of PSD95 also depolarized cVSMCs in pressurized cerebral arteries and induced a strong constriction associated with a loss of functional K V 1 channels. Our findings provide initial evidence that PSD95 is expressed in cVSMCs, and K V 1 channels are one of its important binding partners. PSD95 appears to function as a critical “dilator” scaffold in rat cerebral arteries by increasing the number of functional K V 1 channels at the plasma membrane. Supported by NIH R01 HL097107 (SWR) .