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The Role of IP3 Receptors in Generating Calcium Waves and Cerebral Myogenic Tone
Author(s) -
Muftia Rania,
Welsh Suzanne Brett,
ElRahman Rasha Abd,
Jones Peter,
Chen Wayne,
Welsh Donald
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.1033.3
Subject(s) - thapsigargin , chemistry , depolarization , ryanodine receptor , biophysics , myosin light chain kinase , phosphorylation , receptor , medicine , fura 2 , endoplasmic reticulum , microbiology and biotechnology , endocrinology , biology , biochemistry , cytosol , enzyme
This study of the cerebral vasculature examined whether: 1) elevated intravascular pressure induces asynchronous Ca 2+ waves by activating IP 3 receptors; and 2) these events drive myogenic tone development by augmenting myosin light chain phosphorylation (LC 20 ). Rat cerebral arteries pressurized between 20–100 mmHg were examined in the absence and presence of agents that deplete the sarcoplasmic reticulum (SR) of Ca 2+ or block IP 3 receptors. Diameter and membrane potential (V M ) were assessed using conventional techniques whereas Ca 2+ waves and LC 20 phosphorylation were monitored using confocal microscopy and western blot analysis, respectively. Elevated intravascular pressure increased the proportion of smooth muscle cells firing Ca 2+ waves as well as the frequency of these voltage‐independent events. Agents that deplete the SR of Ca 2+ (ryanodine, CPA and Thapsigargin) or block IP 3 receptors (2‐APB or Xestospongin‐C) eliminated Ca 2+ wave generation. The loss of Ca 2+ waves attenuated LC 20 phosphorylation and attenuated myogenic tone development. It did not, however, alter pressure‐induced depolarization in an intact artery In summary, this study shows that pressure‐induced Ca 2+ waves facilitate cerebral myogenic tone by providing a proportion of the Ca 2+ required to activate myosin light chain kinase. Supported by NSERC.