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Disruption of Caffeine‐Induced Constriction in Isolated Cerebral Arteries Following Treatment with siRNA Against STIM 1
Author(s) -
Gonzales Albert Louis,
Earley Scott
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.603.15
Subject(s) - caffeine , stim1 , contraction (grammar) , chemistry , cerebral arteries , constriction , cytosol , endoplasmic reticulum , microbiology and biotechnology , membrane potential , endocrinology , biophysics , medicine , anatomy , biology , biochemistry , enzyme
The regulation of cytosolic free Ca 2+ is crucial for controlling smooth muscle contraction. Ca 2+ release from sarcoplasmic reticulum (SR) stores contribute to the activation of Ca 2+ sensitive ion channels located proximally in the plasma membrane. Regulation of these channels governs membrane potential and the opening of voltage‐gated Ca 2+ channels, ultimately leading to muscle contraction. The stromal‐interacting molecule (STIM) 1 acts as the Ca 2+ ‐sensing protein, and is important for the refilling of SR Ca 2+ stores. In the current study, we use RNAi technology to further characterize the role of STIM1 in caffeine‐induced SR Ca 2+ ‐depletion and arterial constriction. Treatment of intact cerebral arteries with STIM1 siRNA decreased mRNA expression by ~70% compared with controls. Using ratiometric Ca 2+ imaging, we found that caffeine‐induced increases in cytosolic Ca 2+ levels were attenuated in STIM1 siRNA‐treated vessels. Furthermore, using simultaneous video dimensional analysis we found that transient caffeine‐induced constriction of arteries treated with STIM1 siRNA was blunted compared with controls. These data suggest that STIM1 plays a central role in regulating SR Ca 2+ stores responsible for smooth muscle contraction and the maintenance of arterial tone. RO1HL091905 (SE); F31HL094145‐01 (AG)