Unitary TRPV3 channel ca2+ influx events elicit endothelium-dependent dilation of cerebral parenchymal arterioles

Paulo W. Pires, Michelle N. Sullivan, Harry A.T. Pritchard, Jennifer J. Robinson, Scott Earley

Research output: Contribution to journalArticlepeer-review

38 Scopus citations

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 Ca2+ 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 Ca2+ 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 (∆F/F0 = 0.20) than previously characterized TRPV4 (∆F/F0 = 0.06) or TRPA1 (∆F/F0 = 0.13) sparklets, suggesting that TRPV3-mediated Ca2+ influx could have a robust inluence on cerebrovascular tone. In pressure myogra-phy 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 Ca2+-activated K+ (SK) channels. Together, these data suggest that TRPV3 sparklets cause dilation of cerebral paren-chymal arterioles by activating IK and SK channels in the endothe-lium.

Original languageEnglish (US)
Pages (from-to)H2031-H2041
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume309
Issue number12
DOIs
StatePublished - 2015
Externally publishedYes

Keywords

  • Endothelium-dependent hyperpolarization
  • Parenchymal arterioles
  • Transient receptor potential channel
  • Transient receptor potential sparklet
  • Vanilloid transient receptor potential 3

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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