title: Unitary TRPV3 channel Ca2+ influx events elicit endothelium-dependent dilation of cerebral parenchymal arterioles.
abstract: Cerebral parenchymal arterioles (PA) regulate blood flow between pial arteries on the surface of the brain and the deeper microcirculation. Regulation of PA contractility differs from that of pial arteries and is not completely understood. Here, we investigated the hypothesis that the Ca(2+) permeable vanilloid transient receptor potential (TRPV) channel TRPV3 can mediate endothelium-dependent dilation of cerebral PA. Using total internal reflection fluorescence microscopy (TIRFM), we found that carvacrol, a monoterpenoid compound derived from oregano, increased the frequency of unitary Ca(2+) influx events through TRPV3 channels (TRPV3 sparklets) in endothelial cells from pial arteries and PAs. Carvacrol-induced TRPV3 sparklets were inhibited by the selective TRPV3 blocker isopentenyl pyrophosphate (IPP). TRPV3 sparklets have a greater unitary amplitude (ΔF/F0 = 0.20) than previously characterized TRPV4 (ΔF/F0 = 0.06) or TRPA1 (ΔF/F0 = 0.13) sparklets, suggesting that TRPV3-mediated Ca(2+) influx could have a robust influence on cerebrovascular tone. In pressure myography experiments, carvacrol caused dilation of cerebral PA that was blocked by IPP. Carvacrol-induced dilation was nearly abolished by removal of the endothelium and block of intermediate (IK) and small-conductance Ca(2+)-activated K(+) (SK) channels. Together, these data suggest that TRPV3 sparklets cause dilation of cerebral parenchymal arterioles by activating IK and SK channels in the endothelium.
authors.affiliation: Department of Pharmacology, Center for Cardiovascular Research, University of Nevada School of Medicine, Reno, Nevada; and.
authors.forename: Paulo W
authors.identifier: http://orcid.org/0000-0001-5972-4554
authors.initials: PW
authors.lastname: Pires
authors.affiliation: Department of Pharmacology, Center for Cardiovascular Research, University of Nevada School of Medicine, Reno, Nevada; and Department of Biomedical Sciences, Colorado State University, Fort Collins, Colorado.
authors.forename: Michelle N
authors.initials: MN
authors.lastname: Sullivan
authors.affiliation: Department of Pharmacology, Center for Cardiovascular Research, University of Nevada School of Medicine, Reno, Nevada; and.
authors.forename: Harry A T
authors.initials: HA
authors.lastname: Pritchard
authors.affiliation: Department of Biomedical Sciences, Colorado State University, Fort Collins, Colorado.
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Robinson
authors.affiliation: Department of Pharmacology, Center for Cardiovascular Research, University of Nevada School of Medicine, Reno, Nevada; and searley@medicine.nevada.edu.
authors.forename: Scott
authors.initials: S
authors.lastname: Earley
mesh_terms: D000818:Animals; D001160:Arterioles / Q000502:physiology*; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects / Q000235:genetics* / Q000502:physiology*; D002560:Cerebrovascular Circulation / Q000235:genetics* / Q000502:physiology*; D000081007:Cymenes; D004576:Electromyography; D004730:Endothelium, Vascular / Q000502:physiology*; D045782:Hemiterpenes / Q000494:pharmacology; D051660:Intermediate-Conductance Calcium-Activated Potassium Channels / Q000187:drug effects; D008297:Male; D039821:Monoterpenes / Q000494:pharmacology; D009129:Muscle Tonus / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D009943:Organophosphorus Compounds / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D051640:Small-Conductance Calcium-Activated Potassium Channels / Q000187:drug effects; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000502:physiology*; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D000081007:Cymenes; D045782:Hemiterpenes; D051660:Intermediate-Conductance Calcium-Activated Potassium Channels; D039821:Monoterpenes; D009943:Organophosphorus Compounds; D051640:Small-Conductance Calcium-Activated Potassium Channels; D050916:TRPV Cation Channels; C505767:TRPV3 protein, rat; D014665:Vasodilator Agents; C004809:isopentenyl pyrophosphate; C073316:carvacrol; D002118:Calcium
keywords: endothelium-dependent hyperpolarization; parenchymal arterioles; transient receptor potential channel; transient receptor potential sparklet; vanilloid transient receptor potential 3