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Phosphoinositide‐mediated arterial contractions in mice
Author(s) -
Andresen Jon,
Silswal Neerupma,
Qu ChengKui
Publication year - 2009
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.23.1_supplement.lb136
Subject(s) - ryanodine receptor , contraction (grammar) , pi , vascular smooth muscle , endocrinology , medicine , chemistry , thapsigargin , isometric exercise , muscle contraction , calcium , endoplasmic reticulum , biology , biochemistry , smooth muscle
Phosphoinositides are important signaling molecules in the vasculature. Recently, it was demonstrated in skeletal muscle that PI(3,5)P 2 stimulates ryanodine receptors (RyR) resulting in increased cytosolic calcium (Ca 2+ ) levels and enhanced contraction. Using isolated mouse aortas held under isometric tension, we examined the effect of PI(3,5)P 2 on vascular smooth muscle. Exogenous PI(3,5)P 2 (10 −8 M to 3x10 −6 M) elicited concentration‐dependent contraction of the mouse aorta. Unlike PI(3,5)P 2 , the isomers PI(4,5)P 2 and PI(3)P, did not cause contraction. Blockade of RyR with 10 −5 M ryanodine significantly reduced contraction to PI(3,5)P 2 . Depletion of sarcoplasmic (SR) Ca 2+ with 10 −6 M thapsigargin alone, or in combination with ryanodine and caffeine (20 mM) completely abrogated contraction to PI(3,5,)P 2 . Preincubation with 10 −5 M verapamil, however, blocked the sustained, but not the initial phase, of the contraction to PI(3,5)P 2 . It appears that activation of RyR by PI(3,5)P 2 releases Ca 2+ from the SR, which elicits a transient contraction of smooth muscle. Maintained contraction to PI(3,5)P 2 , however, evidently requires extracellular Ca 2+ entry via VDCC. These data suggests that PI(3,5)P 2 may regulate vascular tone through the modulation of cytosolic Ca 2+ levels. This research was supported by an AHA SDG (0735053N) and UMKC start‐up funds.