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Control of TRPV4 and Its Effect on the Lung

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Mechanosensitivity and Mechanotransduction

Part of the book series: Mechanosensitivity in Cells and Tissues ((MECT,volume 4))

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Abstract

The transient receptor potential vanilloid 4 (TRPV4) non-selective cation channel has emerged as a critical channel for initiating the increased vascular permeability induced by high airway or vascular pressures in the lung. TRPV4 gating is regulated by multiple factors: mechanical stress, heat, epoxyeicosatrienoic acids (EETs) – the arachidonic acid metabolites of P450 epoxygenases, and phorbol esters. Increased pulmonary venous pressure and ventilation with high peak inflation pressures increase endothelial calcium influx, nitric oxide production, and vascular permeability in a TRPV4 dependent fashion in intact lungs. The permeability response to excess mechanical stress is attenuated by inhibition of cytosolic phospholipase A2 or P450 epoxygenases, and permeability increases in response to infusion of EETs. Various molecular mechanisms have been implicated for regulating TRPV4 gating, including channel translocation, direct ligand binding and phosphorylation. However, the mechanisms for EET dependent regulation of TRPV4 or amplification of TRPV4 by phosphorylation in intact lungs subjected to mechanical stress have not been clarified.

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Acknowledgements

Research support by NIH HL066299 and HL092992

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Authors and Affiliations

  1. Department of Physiology and Center for Lung Biology, MSB 3074, University of South Alabama, Mobile, AL, 36688, USA

    James C. Parker & Mary I. Townsley

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  1. James C. Parker
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  2. Mary I. Townsley
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Correspondence to James C. Parker .

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Editors and Affiliations

  1. Chemical Department, Moscow State University, Vorobiovy Gory MSU, Moscow, 119899, Russian Federation

    Andre Kamkin

  2. , Department of Fundamental and Applied Ph, Russian State Medical University, Ostrovitjanova Str. 1, Moscow, 117997, Russian Federation

    Irina Kiseleva

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Parker, J.C., Townsley, M.I. (2010). Control of TRPV4 and Its Effect on the Lung. In: Kamkin, A., Kiseleva, I. (eds) Mechanosensitivity and Mechanotransduction. Mechanosensitivity in Cells and Tissues, vol 4. Springer, Dordrecht. https://doi.org/10.1007/978-90-481-9881-8_10

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