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Phosphatidylinositol 3,5‐bisphosphate increases intracellular free Ca2+ in VSMC and elicits vascular contraction
Author(s) -
Silswal Neerupma,
Parelkar Nikhil K,
Andresen Jon
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.986.1
Subject(s) - ryanodine receptor , pi , contraction (grammar) , verapamil , vascular smooth muscle , extracellular , endocrinology , medicine , phosphatidylinositol , intracellular , chemistry , thapsigargin , calcium , biology , biochemistry , signal transduction , smooth muscle
Phosphatidylinositol 3,5‐bisphosphate (PI(3,5)P 2 ) is a newly identified phosphoinositide that is an agonist for the ryanodine receptor (RyR). Immunofluorescence demonstrated that PI(3,5)P 2 was present throughout the wall of the mouse aorta. Application of exogenous PI(3,5)P 2 (10 nM to 3 μM) contracted aortic rings whereas vehicle had no effect. Depletion of intracellular Ca 2+ stores with thapsigargin (10 μM) and ryanodine (10 μM) abrogated contraction to PI(3,5,)P 2 . Verapamil (10 μM), however, blocked the sustained, but notthe initial phase of the contraction to PI(3,5)P 2 . In Fura‐2 Ca 2+ imaging studies of dissociated aortic smooth muscle cells PI(3,5)P 2 concentration‐dependently elevated intracellular Ca 2+ ([Ca 2+ ] in ). Removal of extracellular Ca 2+ , or addition of 10 μM verapamil, substantially decreased the rise in [Ca 2+ ] in caused by PI(3,5)P 2 . In Ca 2+ ‐free buffer, preincubation with either ryanodine or caffeine prevented PI(3,5)P 2 from generating a Ca 2+ response. Addition of La 3+ (100 μM) to block transient receptor potential channels also reduced, but did not abolish the rise of [Ca 2+ ] in caused by PI(3,5)P 2 . Likewise, in aortic rings, La 3+ impaired the contractile response to PI(3,5)P 2 . These data suggest that PI(3,5)P 2 modulates Ca 2+ signaling in vascular smooth muscle cells and contraction in intact arteries. This research was supported by an AHA SDG (0735053N) and UMKC start‐up funds.