Vascular biology

Localized TRPA1 channel Ca2+ signals stimulated by reactive oxygen species promote cerebral artery dilation

Michelle N. Sullivan, Albert L. Gonzales, Paulo W. Pires, Allison Bruhl, Marie Dennis Leo, Wencheng Li, Agathe Oulidi, Frederick Boop, Yumei Feng, Jonathan Jaggar, Donald G. Welsh, Scott Earley

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

Reactive oxygen species (ROS) can have divergent effects in cerebral and peripheral circulations. We found that Ca2+-permeable transient receptor potential ankyrin 1 (TRPA1) channels were present and colocalized with NADPH (reduced form of nicotinamide adenine dinucleotide phosphate) oxidase 2 (NOX2), a major source of ROS, in the endothelium of cerebral arteries but not in other vascular beds. We recorded and characterized ROS-triggered Ca2+ signals representing Ca2+ influx through single TRPA1 channels, which we called "TRPA1 sparklets." TRPA1 sparklet activity was low under basal conditions but was stimulated by NOX-generated ROS. Ca2+ entry during a single TRPA1 sparklet was twice that of a TRPV4 sparklet and ∼200 times that of an L-type Ca2+ channel sparklet. TRPA1 sparklets representing the simultaneous opening of two TRPA1 channels were more common in endothelial cells than in human embryonic kidney (HEK) 293 cells expressing TRPA1. The NOX-induced TRPA1 sparklets activated intermediate-conductance, Ca2+-sensitive K+ channels, resulting in smooth muscle hyperpolarization and vasodilation. NOX-induced activation of TRPA1 sparklets and vasodilation required generation of hydrogen peroxide and lipid-peroxidizing hydroxyl radicals as intermediates. 4-Hydroxy-nonenal, a metabolite of lipid peroxidation, also increased TRPA1 sparklet frequency and dilated cerebral arteries. These data suggest that in the cerebral circulation, lipid peroxidation metabolites generated by ROS activate Ca2+ influx through TRPA1 channels in the endothelium of cerebral arteries to cause dilation.

Original languageEnglish (US)
Article numberra2
JournalScience Signaling
Volume8
Issue number358
DOIs
StatePublished - Jan 6 2015

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Ankyrins
Cerebral Arteries
Blood Vessels
Dilatation
Reactive Oxygen Species
Cerebrovascular Circulation
Metabolites
Lipids
Vasodilation
Lipid Peroxidation
Endothelium
Endothelial cells
NADP
Hydroxyl Radical
Hydrogen Peroxide
Smooth Muscle
Muscle

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Vascular biology : Localized TRPA1 channel Ca2+ signals stimulated by reactive oxygen species promote cerebral artery dilation. / Sullivan, Michelle N.; Gonzales, Albert L.; Pires, Paulo W.; Bruhl, Allison; Leo, Marie Dennis; Li, Wencheng; Oulidi, Agathe; Boop, Frederick; Feng, Yumei; Jaggar, Jonathan; Welsh, Donald G.; Earley, Scott.

In: Science Signaling, Vol. 8, No. 358, ra2, 06.01.2015.

Research output: Contribution to journalArticle

Sullivan, Michelle N. ; Gonzales, Albert L. ; Pires, Paulo W. ; Bruhl, Allison ; Leo, Marie Dennis ; Li, Wencheng ; Oulidi, Agathe ; Boop, Frederick ; Feng, Yumei ; Jaggar, Jonathan ; Welsh, Donald G. ; Earley, Scott. / Vascular biology : Localized TRPA1 channel Ca2+ signals stimulated by reactive oxygen species promote cerebral artery dilation. In: Science Signaling. 2015 ; Vol. 8, No. 358.
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