title: Recruitment of dynamic endothelial Ca2+ signals by the TRPA1 channel activator AITC in rat cerebral arteries.
abstract: OBJECTIVE
  Stimulation of endothelial TRP channels, specifically TRPA1, promotes vasodilation of cerebral arteries through activation of Ca2+ -dependent effectors along the myoendothelial interface. However, presumed TRPA1-triggered endothelial Ca2+ signals have not been described. We investigated whether TRPA1 activation induces specific spatial and temporal changes in Ca2+ 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 Ca2+ dynamics (44 ± 6 events/minute from 26 ± 3 distinct sites in a 3.6 × 10(4) μm2 field). The TRPA1 activator AITC increased Ca2+ signals in a concentration-dependent manner, soliciting new events at distinct sites. Origination of these new events corresponded spatially with TRPA1 densities in IEL holes, and the events were prevented by the TRPA1 inhibitor HC-030031. Concentration-dependent expansion of Ca2+ 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 Ca2+ waves in subintimal smooth muscle.
  
  
  CONCLUSIONS
  Our findings indicate that factors that stimulate TRPA1 channels expand Ca2+ signal-effector coupling at discrete sites along the endothelium to evoke graded cerebral artery vasodilation.
authors.affiliation: Department of Physiology, University of South Alabama College of Medicine, Mobile, Alabama, USA.
authors.forename: Xun
authors.initials: X
authors.lastname: Qian
authors.forename: Michael
authors.initials: M
authors.lastname: Francis
authors.forename: Viktoriya
authors.initials: V
authors.lastname: Solodushko
authors.forename: Scott
authors.initials: S
authors.lastname: Earley
authors.forename: Mark S
authors.initials: MS
authors.lastname: Taylor
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D002536:Cerebral Arteries / Q000187:drug effects / Q000502:physiology*; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects / Q000502:physiology; D017879:Isothiocyanates / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D051381:Rats; D000074025:TRPA1 Cation Channel; D050052:TRPC Cation Channels / Q000819:agonists* / Q000502:physiology*; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
chemical_list: D017879:Isothiocyanates; D000074025:TRPA1 Cation Channel; D050052:TRPC Cation Channels; C480976:Trpa1 protein, rat; C004471:allyl isothiocyanate; D002118:Calcium