Opposing actions of TRPV4 channel activation in the lung vasculature

Ke, Sunkui; Chen, Lan; Duan, Hongbing; Tu, Yuan-rong

doi:10.1016/j.resp.2015.08.003

Cited by 12 publications

(8 citation statements)

References 38 publications

(44 reference statements)

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“…administration of ACh was unaffected by systemic administration of the TRPV4 antagonist GSK2193874 (204). Interestingly, Ke et al reported that endothelial TRPV4 stimulation with the agonist GSK1016790A significantly increased pulmonary vascular resistance in isolated perfused lungs (136). Activation of smooth muscle TRPV4 in the absence of endothelial signaling may also contribute to increased pulmonary artery pressure (204).…”

Section: Functional Roles Of Trp Channels In the Vascular Endotheliummentioning

confidence: 99%

Transient Receptor Potential Channels and Endothelial Cell Calcium Signaling

Thakore

Earley

2019

Comprehensive Physiology

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The vascular endothelium is a broadly distributed and highly specialized organ. The endothelium has a number of functions including the control of blood vessels diameter through the production and release of potent vasoactive substances or direct electrical communication with underlying smooth muscle cells, regulates the permeability of the vascular barrier, stimulates the formation of new blood vessels, and influences inflammatory and thrombotic processes. Endothelial cells that make up the endothelium express a variety of cell-surface receptors and ion channels on the plasma membrane that are capable of detecting circulating hormones, neurotransmitters, oxygen tension, and shear stress across the vascular wall. Changes in these stimuli activate signaling cascades that initiate an appropriate physiological response. Increases in the global intracellular Ca 2+ concentration and localized Ca 2+ signals that occur within specialized subcellular microdomains are fundamentally important components of many signaling pathways in the endothelium. The transient receptor potential (TRP) channels are a superfamily of cationpermeable ion channels that act as a primary means of increasing cytosolic Ca 2+ in endothelial cells. Consequently, TRP channels are vitally important for the major functions of the endothelium. In this review, we provide an in-depth discussion of Ca 2+-permeable TRP channels in the endothelium and their role in vascular regulation.

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Section: Functional Roles Of Trp Channels In the Vascular Endotheliummentioning

confidence: 99%

Transient Receptor Potential Channels and Endothelial Cell Calcium Signaling

Thakore

Earley

2019

Comprehensive Physiology

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“…The channel was suggested to increase pulmonary vascular resistance (Ke et al . ) and strengthen cell–cell junctions (Akazawa et al . ) yet excessive TRPV4 activation triggers a circulatory collapse due to the breakdown of microvascular permeability barriers (Willette et al .…”

Section: Introductionmentioning

confidence: 99%

Calcium influx through TRPV4 channels modulates the adherens contacts between retinal microvascular endothelial cells

Phuong

Redmon

Yarishkin

et al. 2017

The Journal of Physiology

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The identity of microvascular endothelial (MVE) mechanosensors that sense blood flow in response to mechanical and chemical stimuli and regulate vascular permeability in the retina is unknown. Using immunohistochemistry, calcium imaging, electrophysiology, impedance measurements and vascular permeability assays, we show that the transient receptor potential isoform 4 (TRPV4) plays a major role in Ca /cation signalling, cytoskeletal remodelling and barrier function in retinal microvasculature in vitro and in vivo. Human retinal MVE cells (HrMVECs) predominantly expressed Trpv1 and Trpv4 transcripts, and TRPV4 was broadly localized to the plasma membrane of cultured cells and intact blood vessels in the inner retina. Treatment with the selective TRPV4 agonist GSK1016790A (GSK101) activated a nonselective cation current, robustly elevated [Ca ] and reversibly increased the permeability of MVEC monolayers. This was associated with disrupted organization of endothelial F-actin, downregulated expression of occludin and remodelling of adherens contacts consisting of vascular endothelial cadherin (VE-cadherin) and β-catenin. In vivo, GSK101 increased the permeability of retinal blood vessels in wild type but not in TRPV4 knockout mice. Agonist-evoked effects on barrier permeability and cytoskeletal reorganization were antagonized by the selective TRPV4 blocker HC 067047. Human choroidal endothelial cells expressed lower TRPV4 mRNA/protein levels and showed less pronounced agonist-evoked calcium signals compared to MVECs. These findings indicate a major role for TRPV4 in Ca homeostasis and barrier function in human retinal capillaries and suggest that TRPV4 may differentially contribute to the inner vs. outer blood-retinal barrier function.

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“…In isolated constantly perfused mouse lungs, GSK1016790A increased pressure suggesting that it induced vasoconstriction (Ke et al . ). However, as previously pointed out by others, a major limitation of these studies was that they were performed in perfused lungs without ventilation (Gollasch & Kubler ).…”

Section: Role Of Endothelial Trpv4 Channels and Kca31 In Endotheliummentioning

confidence: 97%

Emerging roles of calcium-activated K channels and TRPV4 channels in lung oedema and pulmonary circulatory collapse

et al. 2016

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It has been suggested that the transient receptor potential cation (TRP) channel subfamily V (vanilloid) type 4 (TRPV4) and intermediate conductance calcium-activated potassium (KCa3.1) channels contribute to endothelium-dependent vasodilation. Here, we summarize very recent evidence for a synergistic interplay of TRPV4 and KCa3.1 channels in lung disease. Among the endothelial Ca 2+ -permeable TRPs, TRPV4 is best characterized and produces arterial dilation by stimulating Ca 2+ -dependent nitric oxide synthesis and endothelium-dependent hyperpolarization. Besides these roles, some TRP channels control endothelial/epithelial barrier functions and vascular integrity, while KCa3.1 channels provide the driving force required for Cl À and water transport in some cells and most secretory epithelia. The three conditions, increased pulmonary venous pressure caused by left heart disease, high inflation pressure and chemically induced lung injury, may lead to activation of TRPV4 channels followed by Ca 2+ influx leading to activation of KCa3.1 channels in endothelial cells ultimately leading to acute lung injury. We find that a deficiency in KCa3.1 channels protects against TRPV4-induced pulmonary arterial relaxation, fluid extravasation, haemorrhage, pulmonary circulatory collapse and cardiac arrest in vivo. These data identify KCa3.1 channels as crucial molecular components in downstream TRPV4 signal transduction and as a potential target for the prevention of undesired fluid extravasation, vasodilatation and pulmonary circulatory collapse.

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Opposing actions of TRPV4 channel activation in the lung vasculature

Cited by 12 publications

References 38 publications

Transient Receptor Potential Channels and Endothelial Cell Calcium Signaling

Transient Receptor Potential Channels and Endothelial Cell Calcium Signaling

Calcium influx through TRPV4 channels modulates the adherens contacts between retinal microvascular endothelial cells

Emerging roles of calcium-activated K channels and TRPV4 channels in lung oedema and pulmonary circulatory collapse

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