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Cited by 552Ion Channels and ReceptorsCalcium signaling and nucleotide metabolismIon channel regulation and function

Elementary Ca 2+ Signals Through Endothelial TRPV4 Channels Regulate Vascular Function

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Sonkusare, Swapnil K., Bonev, Adrian D., Ledoux, Jonathan, Liedtke, Wolfgang, Kotlikoff, Michael I., Heppner, Thomas J., Hill-Eubanks, David C., Nelson, Mark T.·2012·Science
DOI 10.1126/science.1216283PMC PMC3715993
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Abstract

Blood Pressure Gauge: Endothelial cells line blood vessels and, by interacting with smooth muscle, can help to control blood flow. Sonkusare et al. (p. 597 ; see the Perspective by Lederer et al. ) describe how signaling in endothelial cells controls contraction of surrounding smooth muscle cells, which provides an important mechanism for control of blood pressure. A calcium-sensitive fluorescent protein was expressed in endothelial cells of mouse arteries to image small changes in calcium concentration that appear to represent opening of single TRPV4 ion channels and consequent influx of calcium into the cell. Clustering of the channels allowed cooperative activation of a handful of channels, which appeared to produce a sufficient calcium signal to open another set of calcium-sensitive potassium channels. The resulting depolarization of the endothelial cells then passes an electrical connection to smooth muscle cells through gap junctions.

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Crossref · 10.1126/science.1216283

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  • TRP channels regulate Ca2+ influx into brain endothelium that releases soluble factors such as NO, prostaglandins, and endothelial-derived hyperpolarizing factor, initiating endothelium-dependent vasodilation.

    “TRP channels regulate Ca 2 + influx into brain endothelium that releases soluble factors such as NO, prostaglandins, and endothelial-derived hyperpolarizing factor initiating endothelium-dependent vasodilation (553).”

    From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [553]

    The paper’s Abstract and accompanying text describe TRPV4-mediated Ca2+ influx and endothelium-dependent dilation, and identify NO, prostaglandins, and EDHF as broad categories of Ca2+-dependent vasodilatory influences. But its experiments concern resistance arteries, not specifically brain endothelium; they link TRPV4-mediated dilation to the EDHF pathway, finding that inhibition of NO synthase and cyclooxygenase did not affect it. The paper also describes EDHF signaling primarily as hyperpolarizing current spreading through gap junctions, rather than release of a soluble factor. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • Abluminal transient receptor potential (TRP) channels are expressed both in arterial endothelium and brain microvascular endothelial cell lines.

    “The abluminal transient receptor potential (TRP) channels, also known as nonselective Ca 2 + -conducting cation channels, are expressed both in arterial endothelium (553) and brain microvascular endothelial cell lines (38, 249).”

    From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [553]

    The paper’s Abstract reports TRPV4 cation-channel activity in the endothelium of resistance arteries, supporting the arterial-endothelium part of the claim. The passages do not identify the channels as abluminal. The citing sentence assigns the brain microvascular cell-line claim to other references (38, 249), not this source. (LLM, conf=0.83)

    Experimental — accuracy not yet measured

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Cites

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Research works printed but not linked: 20

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Authors
Sonkusare, S. K., Bonev, A. D., Ledoux, J., Liedtke, W., Kotlikoff, M. I., Heppner, T. J., Hill-Eubanks, D. C., & Nelson, M. T.
Affiliations
  • University of Vermont (US)
  • Duke University (US)
  • Cornell University (US)
  • Department of Pharmacology, College of Medicine, University of Vermont, Burlington, VT 05405, USA.
Corresponding author
Nelson, Mark T.
ORCID
Venue
Science
Publisher
American Association for the Advancement of Science (AAAS)
Published
2012-05-04
Volume
336
Issue
6081
Pages
597-601
ISSN
  • 0036-8075 (ISSN-L)
  • 1095-9203
DOI
10.1126/science.1216283
PMC
PMC3715993
OpenAlex
W2048492290
Cited by
552
References
1
Citations by year
2026: 28 · 2025: 21 · 2024: 23 · 2023: 42 · 2022: 33 · 2021: 46 · 2020: 38 · 2019: 25 · 2018: 44 · 2017: 41 · 2016: 44 · 2015: 46 · 2014: 61 · 2013: 31 · 2012: 29
FWCI
29.79
Type
journal article
Language
en
Open access
Locations
  • Science (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • Research Explorer (The University of Manchester) (submittedVersion)
Funders
  • National Heart, Lung, and Blood Institute (R01HL044455, HL-044455, P01HL095488, R01HL098243)
  • National Institute of General Medical Sciences (GM086736, R01GM086736)
  • National Institute of Diabetes and Digestive and Kidney Diseases (R37DK053832)
  • National Center for Research Resources (P20RR016435)
Topics
  • Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Calcium signaling and nucleotide metabolism
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
Keywords
TRPV4 channel, endothelial calcium signaling, vascular smooth muscle tone, vasodilation, resistance arteries, IK channels, small conductance calcium-activated potassium channels, muscarinic receptor signaling, endothelium
MeSH terms
Animals, Calcium, Endothelium, Vascular, Leucine, Mesenteric Arteries, Mice, Inbred C57BL, Mice, Transgenic, Receptors, Muscarinic, Sulfonamides, Vasodilation, Signal Transduction, Ion Channel Gating, Patch-Clamp Techniques, Calcium Signaling, Endothelial Cells, TRPV Cation Channels, Mice, Small-Conductance Calcium-Activated Potassium Channels, Intermediate-Conductance Calcium-Activated Potassium Channels

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