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TRPV4 Ca 2+ sparklets in myoendothelial projections (MEPs) regulate vascular function
Author(s) -
Sonkusare Swapnil K,
Bonev Adrian D.,
Dalsgaard Thomas,
Santana Luis F,
Kotlikoff Michael I,
Nelson Mark T
Publication year - 2013
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.27.1_supplement.916.5
Subject(s) - transient receptor potential channel , trpv4 , chemistry , muscarinic acetylcholine receptor , vasodilation , agonist , carbachol , inward rectifier potassium ion channel , microbiology and biotechnology , mesenteric arteries , protein kinase c , biophysics , receptor , endocrinology , pharmacology , medicine , ion channel , signal transduction , biochemistry , biology , artery
Endothelial cells (ECs) lining blood vessels regulate vascular tone. MEPs connect ECs to adjacent smooth muscle cells (SMCs) via gap junctions. We discovered elementary Ca 2+ signals (“sparklets”) through single TRPV4 (transient receptor potential vanilloid 4) channels at MEPs (Sonkusare et. al., Science, 2012). TRPV4 sparklets dilate 3 rd order mouse mesenteric arteries (MAs) via EC intermediate‐conductance, Ca 2+ sensitive K + (IK) channels. The current study elucidates the mechanism by which muscarinic receptor stimulation dilates MAs via TRPV4 channels. Carbachol (CCh) increased sparklets (5‐fold) ONLY at MEPs, and not elsewhere on the EC membrane. Protein kinase C (PKC) activation similarly increased sparklets only at MEPs. CCh‐activation of sparklets was prevented by PKC inhibitor Go‐6976. Inward rectifier K + (Kir) currents were present in ECs but not in SMCs. Dilations to CCh, TRPV4 agonist GSK1016790A, and IK/SK opener NS309 were inhibited (70%) by Kir channel blocker Ba 2+ . The results support a MEP‐localized signaling circuit of PKC‐TRPV4‐IK‐Kir channels which mediates vasodilatory input to the SM.