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Elementary TRPV4 Ca 2+ events in intact vascular endothelium
Author(s) -
Sonkusare Swapnil K.,
Bonev Adrian D.,
Tallini Yvonne N.,
Kotlikoff Michael I.,
Nelson Mark T.
Publication year - 2011
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.25.1_supplement.1082.1
Subject(s) - chemistry , endothelium , biophysics , medicine , biology
Transient receptor potential vanilloid 4 (TRPV4) channel serves as a Ca 2+ influx pathway in endothelial cells (ECs). The objective of this study was to identify elementary TRPV4 Ca 2+ events in vascular ECs. We used third‐order mesenteric arteries (MAs) from mice that express Ca 2+ biosensor (GCaMP2) selectively in ECs. TRPV4 agonist GSK1016790A (GSK, 10 nM) produced EC‐dependent dilation of pressurized MAs. High speed confocal imaging of slit‐open MAs revealed that TRPV4 agonists (GSK, 4α‐PDD, 11,12‐EET) activate local Ca 2+ events (“TRPV4 Ca 2+ sparklets”) in ECs in absence of Ca 2+ release from intracellular stores. Fractional fluorescence changes (ΔF/F 0 ) for 19 event sites showed a quantal level of 0.22 ± 0.03. Mean open probability (NPs, N = number of quanta, Ps = probability of occurrence) of the sparklets at a site was 0.46 ± 0.06 (n = 10 sites), 0.19 ± 0.03 (n = 5 sites) and 0.57 ± 0.19 (n = 5 sites) for GSK (10 nM), 4α‐PDD (5 μM) and 11, 12‐EET (1 μM), respectively. TRPV4 inhibitor HC067047 (1 μM) significantly reduced NPs of GSK‐induced sparklets to 0.16 ± 0.05 (n = 5 sites, p<0.05). In conclusion, this is the first detection of elementary TRPV4 Ca 2+ sparklets that initiate EC‐dependent vasodilation of resistance arteries. Supported by AHA‐PHA 10POST3690006 (SKS) and NIH HL44455 (MTN).