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Recruitment of dynamic cerebral artery endothelial Ca2+ signals by the TRPA1 channel activator AITC
Author(s) -
Taylor Mark Stephen,
Qian Xun,
Francis Michael,
Earley Scott,
Solodushko Viktoriya
Publication year - 2012
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.26.1_supplement.853.2
Subject(s) - vasodilation , transient receptor potential channel , cerebral arteries , chemistry , medicine , endothelium , activator (genetics) , biophysics , endocrinology , receptor , biology
Real‐time regulation of vascular tone by endothelial Ca 2+ signals is a crucial determinant of blood flow. Recent findings suggest that transient receptor potential (TRP) channels, particularly TRPA1, may play a key role in activating endothelial Ca 2+ ‐dependent effectors in cerebral arteries to promote acute vasodilation. In the current study, we employed high‐speed confocal imaging and a novel analysis algorithm to evaluate the impact of TRPA1 channel activation on Ca 2+ signals in the endothelium of rat cerebral arteries and assess its relationship to vasodilation. We found that endothelial cells of rat cerebral arteries exhibit widespread basal Ca 2+ dynamics (44 ± 6 events at 26 ± 3 distinct sites per minute in a 3.6×10 4 μm 2 field). The TRPA1 activator allyl isothiocyanate (AITC) increased Ca 2+ signals in a concentration dependent manner, primarily by soliciting new events at distinct sites along the intima (56 ± 5% and 52 ± 4% increase in events and sites, respectively, at 60 μM). These stimulated events corresponded spatially with TRPA1 channel densities within holes in the internal elastic lamina (IEL) and were blocked by the TRPA1‐specific inhibitor HC‐030031. The concentration‐dependent expansion of Ca 2+ events in response to AITC correlated precisely with the dilation of pressurized cerebral arteries (p = 0.93 by F‐test comparison of nonlinear regression curve fits). Correspondingly, AITC caused rapid endothelium‐dependent suppression of pro‐contractile asynchronous Ca 2+ waves in subintimal smooth muscle cells. The current findings suggest that factors evoking stimulation of TRPA1 channels trigger and expand discrete Ca 2+ signal‐effector coupling sites along the endothelium to evoke graded cerebral artery vasodilation. Supported by NIH R01 HL085887 and R01 HL091905.