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Mechanotransduction by TRP Channels: General Concepts and Specific Role in the Vasculature

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Abstract

Transient receptor potential (TRP) ion channel superfamily is involved in sensing and transmission of a broad variety of external or internal stimuli, including but not limited to mechanical stress. Based on homology analysis, genetic and molecular studies have recently identified TRP channels in different tissues, comprising blood vessels. In invertebrates, many TRP channels including five TRPV channels identified in Caenorhabditis elegans and two in Drosophila have been implicated in mechanosensory behaviors as molecular basis of volume regulation, hearing and touch sensitivity. Consistently, in mammals many TRP family members such as TRPC1, TRPC3, TRPC6, TRPM4, TRPM7, TRPN1, TRPA1, TRPY1, TRPP1, TRPP2, and notably, TRPV1, TPRV2 as well as TRPV4 have been reported to be involved in mechanotransduction. This review summarizes recent and at times controversial findings on the role and regulation of TRP channels in mechanotransduction. Specifically, we highlight the relevance of TRPV channels in vascular regulation and focus on TRPV4 in the vascular system of the lung, which is constantly exposed to a unique combination of circumferential and longitudinal strains. In light of our observation in intact pulmonary microvessels that mechanical stress induced Ca2+ signaling in endothelial cells is closely related to TRPV4 activity, we postulate that TRPV4 plays a critical role in lung vascular mechanotransduction. The progress in this rapidly expanding field may allow for the identification of new molecular targets and the development of new therapeutic approaches in a number of intractable diseases related to mechanical stress.

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Acknowledgments

We thank Julia Hoffmann and Stephanie Kaestle for Western blot analyses shown in Fig. 4, Dr. Joerg Baeurle for immunohistological images in Fig. 4, and Dr. Wolfgang Liedtke, Departments of Medicine, Neurology, and Neurobiology, Duke University, Durham, NC, for kind provision of TRPV4−/− mice. This article was supported by the Deutsche Forschungsgemeinschaft (Ku1218/4; Ku1218/5), Canadian Institutes of Health Research (CIHR); and the Kaiserin-Friedrich Foundation, Berlin, Germany.

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  1. The Keenan Research Centre, Li Ka Shing Knowledge Institute, St. Michael’s Hospital, 30 Bond Street, Bond Wing 2-021, Toronto, ON, M5B 1W8, Canada

    Jun Yin & Wolfgang M. Kuebler

  2. Department of Surgery, University of Toronto, Toronto, ON, Canada

    Wolfgang M. Kuebler

  3. Institute of Physiology, Charité-Universitätsmedizin Berlin, Berlin, Germany

    Jun Yin & Wolfgang M. Kuebler

  4. German Heart Institute Berlin, Berlin, Germany

    Jun Yin & Wolfgang M. Kuebler

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Yin, J., Kuebler, W.M. Mechanotransduction by TRP Channels: General Concepts and Specific Role in the Vasculature. Cell Biochem Biophys 56, 1–18 (2010). https://doi.org/10.1007/s12013-009-9067-2

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