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Recruitment of Dynamic Endothelial Ca 2+ Signals by the TRPA 1 Channel Activator AITC in Rat Cerebral Arteries
Author(s) -
Qian Xun,
Francis Michael,
Solodushko Viktoriya,
Earley Scott,
Taylor Mark S.
Publication year - 2013
Publication title -
microcirculation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.793
H-Index - 83
eISSN - 1549-8719
pISSN - 1073-9688
DOI - 10.1111/micc.12004
Subject(s) - cerebral arteries , vasodilation , chemistry , transient receptor potential channel , activator (genetics) , biophysics , endothelium , trpv4 , microbiology and biotechnology , medicine , endocrinology , biology , biochemistry , receptor
Objective Stimulation of endothelial TRP channels, specifically TRPA 1, promotes vasodilation of cerebral arteries through activation of Ca 2+ ‐dependent effectors along the myoendothelial interface. However, presumed TRPA 1‐triggered endothelial Ca 2+ signals have not been described. We investigated whether TRPA 1 activation induces specific spatial and temporal changes in Ca 2+ signals along the intima that correlates with incremental vasodilation. Methods Confocal imaging, immunofluorescence staining, and custom image analysis were employed. Results We found that endothelial cells of rat cerebral arteries exhibit widespread basal Ca 2+ dynamics (44 ± 6 events/minute from 26 ± 3 distinct sites in a 3.6 × 10 4 μ m 2 field). The TRPA 1 activator AITC increased Ca 2+ signals in a concentration‐dependent manner, soliciting new events at distinct sites. Origination of these new events corresponded spatially with TRPA 1 densities in IEL holes, and the events were prevented by the TRPA 1 inhibitor HC ‐030031. Concentration‐dependent expansion of Ca 2+ events in response to AITC correlated precisely with dilation of pressurized cerebral arteries ( p = 0.93 by F ‐test). Correspondingly, AITC caused rapid endothelium‐dependent suppression of asynchronous Ca 2+ waves in subintimal smooth muscle. Conclusions Our findings indicate that factors that stimulate TRPA 1 channels expand Ca 2+ signal‐effector coupling at discrete sites along the endothelium to evoke graded cerebral artery vasodilation.