ArticleProceedings of the National Academy of Sciences of the United States of America2012
Low intravascular pressure activates endothelial cell TRPV4 channels, local Ca2+ events, and IKCa channels, reducing arteriolar tone.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 113 papers.
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Who cites it
113 citing papers in PubMed.
- 25+ Years of TRPV4: From Discovery to Translational Horizons.Research square · 2026Article
- Guidelines for evaluating endothelial function in vascular tissue.American journal of physiology. Heart and circulatory physiology · 2026Review
- TMEM16A channel signalling microdomains in the regulation of vascular function.The Journal of physiology · 2026Review
- The Emerging Role of Endothelial Ion Channels in the Control of Human Microcirculation.International journal of molecular sciences · 2026Review
- The machinery of healthy vasodilatation: an overview.Pflugers Archiv : European journal of physiology · 2025Review
- Pericyte Electrical Signalling and Brain Haemodynamics.Basic & clinical pharmacology & toxicology · 2025Review
- Increased TRPV4 Channel Expression Enhances and Impairs Blood Vessel Function in Hypertension.Hypertension (Dallas, Tex. : 1979) · 2025Article
- Activation of Piezo1 and TRPV4 channels contributes to hCMEC/D3 cell mechano-sensing.Frontiers in physiology · 2025Article
- A QUARTER CENTURY OF CALCIUM-PERMEABLE ION CHANNEL, TRPV4: PERSPECTIVES ON EXPRESSION AND FUNCTION IN ENDOTHELIAL CELLS-TIME TO TRANSLATE.Transactions of the American Clinical and Climatological Association · 2025Review
- TMAO Impairs Mouse Aortic Vasodilation by Inhibiting TRPV4 Channels in Endothelial Cells.Journal of cardiovascular translational research · 2024Article
- Role of transient receptor potential channels in the regulation of vascular tone.Drug discovery today · 2024Review
- Single-Cell RNA-Seq Reveals Coronary Heterogeneity and Identifies CD133Arteriosclerosis, thrombosis, and vascular biology · 2024Article
- Electro-metabolic signaling.The Journal of general physiology · 2024Article
- Myoendothelial feedback in mouse mesenteric resistance arteries is similar between the sexes, dependent on nitric oxide synthase, and independent of TPRV4.American journal of physiology. Heart and circulatory physiology · 2024Article
- Cracking the Endothelial Calcium (CaInternational journal of molecular sciences · 2023Review
- Kinase Inhibitors in Genetic Diseases.International journal of molecular sciences · 2023Review
- Tracking endothelium-dependent NO release in pressurized arteries.Frontiers in physiology · 2023Article
- Endothelial IK and SK channel activation decreases pulmonary arterial pressure and vascular remodeling in pulmonary hypertension.Pulmonary circulation · 2023Article
- Alleviation of allergic conjunctivitis by (±)5(6)-dihydroxy-8Z,11Z,14Z,17Z-eicosatetraenoic acid in mice.Frontiers in pharmacology · 2023Article
- Oxidative Regulation of Vascular CaAntioxidants (Basel, Switzerland) · 2022Review
53 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors.
Funding
Abstract
Endothelial cell (EC) Ca(2+)-activated K channels (SK(Ca) and IK(Ca) channels) generate hyperpolarization that passes to the adjacent smooth muscle cells causing vasodilation. IK(Ca) channels focused within EC projections toward the smooth muscle cells are activated by spontaneous Ca(2+) events (Ca(2+) puffs/pulsars). We now show that transient receptor potential, vanilloid 4 channels (TRPV4 channels) also cluster within this microdomain and are selectively activated at low intravascular pressure. In arterioles pressurized to 80 mmHg, ECs generated low-frequency (~2 min(-1)) inositol 1,4,5-trisphosphate receptor-based Ca(2+) events. Decreasing intraluminal pressure below 50 mmHg increased the frequency of EC Ca(2+) events twofold to threefold, an effect blocked with the TRPV4 antagonist RN1734. These discrete events represent both TRPV4-sparklet- and nonsparklet-evoked Ca(2+) increases, which on occasion led to intracellular Ca(2+) waves. The concurrent vasodilation associated with increases in Ca(2+) event frequency was inhibited, and basal myogenic tone was increased, by either RN1734 or TRAM-34 (IK(Ca) channel blocker), but not by apamin (SK(Ca) channel blocker). These data show that intraluminal pressure influences an endothelial microdomain inversely to alter Ca(2+) event frequency; at low pressures the consequence is activation of EC IK(Ca) channels and vasodilation, reducing the myogenic tone that underpins tissue blood-flow autoregulation.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.