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Basal and ACh‐stimulated intracellular Ca 2+ signals in intact endothelium originate from IP 3 ‐sensitive stores
Author(s) -
Ledoux Jonathan,
Bonev Adrian D.,
Nelson Mark T.
Publication year - 2007
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.21.6.a861
Subject(s) - intracellular , endothelium , ryanodine receptor , acetylcholine , biophysics , microbiology and biotechnology , calcium in biology , calcium , inositol trisphosphate receptor , calcium signaling , biology , chemistry , endocrinology , receptor , inositol , medicine , biochemistry
Intracellular Ca 2+ in the endothelium regulates vascular function. However, endothelial Ca 2+ signaling is highly dynamic. Endothelial Ca 2+ signaling was investigated in intact endothelium of cut‐open mesenteric arteries from mouse, using the Ca 2+ sensitive dye, Fluo‐4, and a laser scanning confocal microscope. Endothelial Ca 2+ events consisted of waves and oscillations that are stimulated by acetylcholine (ACh, 10 μM). Blocking SK and IK channels had no acute effect on basal Ca 2+ signals, although the global Ca 2+ concentration was reduced by 15 ± 5%. In contrast, depletion of intracellular Ca 2+ stores by CPA (30 μM) decreased Ca 2+ event frequency, indicating that Ca 2+ events originate from intracellular Ca 2+ sources. Ryanodine (50 μM) had little, if any, influence on endothelial Ca 2+ events, suggesting that RyRs are not involved in endothelial Ca 2+ signaling. However, inhibition of IP 3 receptors (IP 3 Rs) with Xestospongin C (50 μM) almost completely abolished basal Ca 2+ events and blocked their enhancement by ACh. Similar results were obtain by U‐73122 (10 μM), suggesting that IP 3 ‐mediated calcium release from internal stores generate the endothelial Ca 2+ signals. Therefore, dynamic Ca 2+ signals in mouse endothelium are not directly dependent on membrane potential, and mainly originate from activation of IP 3 Rs. Supported by NIH (HL44455 & HL63722) and CIHR.