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IP3R‐dependent modulation of endothelial Ca2+ dynamics by CaMKII in mouse mesenteric arteries
Author(s) -
Toussaint Fanny,
Charbel Chimène,
Blanchette Alexandre,
Ledoux Jonathan
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.923.16
Subject(s) - ionomycin , thapsigargin , serca , intracellular , chemistry , extracellular , microbiology and biotechnology , endoplasmic reticulum , calcium , medicine , endocrinology , biology , biochemistry , atpase , organic chemistry , enzyme
Local calcium dynamics such as Ca 2+ pulsars appear to have a significant impact on endothelial function. These Ca 2+ pulsars result from the spontaneous release of Ca 2+ by IP 3 receptors (IP 3 R) localized within the myoendothelial junction (MJ). We have recently shown that CaMKII, a Ca 2+‐ dependent kinase decoding Ca 2+ oscillations, is activated by Ca 2+ pulsars. However, CaMKII also regulates intracellular Ca 2+ homeostasis in other cell types. CaMKII regulation of endothelial intracellular Ca 2+ dynamics in native endothelium was then undertaken by confocal microscopy. Exposure to KN‐93, a CaMKII inhibitor, stimulated Ca 2+ pulsar. In the absence of extracellular Ca 2+ , exposure to ionomycin provoked an increase in intracellular Ca 2+ , indicative of the endoplasmic reticulum (ER) content in Ca 2+ . Interestingly, preincubation with KN‐93 significantly impaired the ER Ca 2+ content (−62%). However, SERCA inhibition by thapsigargin did not significantly alter the ionomycin‐induced Ca 2+ increase in the presence of KN‐93. These results suggest that CaMKII regulates endothelial Ca 2+ through the modulation of IP 3 R activity. Immunohistochemistry revealed a progressive intrusion of the different isoforms (IP 3 R2>;IP 3 R1>;IP 3 R3) within the MJ. Therefore, this study suggests that endothelial CaMKII inhibits Ca 2+ pulsars through IP 3 R1/2 phosphorylation. Supported by FRQS, FICM, CFI and HSFC.