Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2013 Feb;61(2):113-9.
doi: 10.1097/FJC.0b013e318279ba42.

TRPV4 and the regulation of vascular tone

Jessica A Filosa  1 , Xiaoqiang Yao, Geraldine Rath
Affiliations
Review

TRPV4 and the regulation of vascular tone

Jessica A Filosa et al. J Cardiovasc Pharmacol. 2013 Feb.

Abstract

Recent studies have introduced the importance of transient receptor potential vanilloid subtype 4 (TRPV4) channels in the regulation of vascular tone. TRPV4 channels are expressed in both endothelium and vascular smooth muscle cells and can be activated by numerous stimuli including mechanical (eg, shear stress, cell swelling, and heat) and chemical (eg, epoxyeicosatrienoic acids, endocannabinoids, and 4α-phorbol esters). In the brain, TRPV4 channels are primarily localized to astrocytic endfeet processes, which wrap around blood vessels. Thus, TRPV4 channels are strategically localized to sense hemodynamic changes and contribute to the regulation of vascular tone. TRPV4 channel activation leads to smooth muscle cell hyperpolarization and vasodilation. Here, we review recent findings on the cellular mechanisms underlying TRPV4-mediated vasodilation; TRPV4 channel interaction with other proteins including transient receptor potential channel 1, small conductance (K(Ca)2.3), and large conductance (K(Ca)1.1) calcium-activated potassium-selective channels; and the importance of caveolin-rich domains for these interactions to take place.

PubMed Disclaimer

Figures

Figure 1
Figure 1. Contribution of TRPV4 channels to the regulation of vascular tone
As shown, heteromeric TRPV4-TRPC1 channels expressed in endothelial cells can be activated by shear stress, agonists (4αPDD, GSK1016790A) and epoxyeicosatrienoic acids (EETs) resulting in an increase in intracellular Ca2+and the release of various vasoactive substances such as EETs, nitric oxide (NO) and prostaglandin (PGI2) leading to vasodilation. In addition, TRPV4 channels in caveolae interact with small conductance potassium channels (SK) contributing to the release of K+from endothelial cells. In smooth muscle cells, K+-induced hyperpolarization is mediated through the activation of the Na/K pump as well as inwardly rectifying potassium channels (Kir). TRPV4-TRPC1 channels in smooth muscle cells are activated by EETs which trigger Ca2+sparks from ryanodine receptors and the subsequent activation of large conductance calcium-activated potassium-selective channels (BK) resulting in smooth muscle cell hyperpolarization and vasodilation. In cerebral parenchymal arterioles, the abluminal side of the vessel is surrounded by astrocytic endfeet processes which also modulate vascular tone. Glutamate-mediated rise in intracellular Ca2+leads to vasodilation through activation of KCa1.1 channels, K+release and activation of Kir channels in smooth muscle cells. The rise in intracellular Ca2+stimulates phospholipase A2(PLA2) and mobilizes arachidonic acid (AA) which then is metabolized to form EETs (among other signals); EETs released at the gliovascular interface activates TRPV4 channels in astrocytic endfeet processes further contributing to the rise in intracellular Ca2+and K+channel signaling. In perivascular nerves, TRPV4 channel activation has been associated with the release of calcitonin gene-related peptide (CGRP) activation of G-protein coupled receptors (GPCR) in smooth muscle cells and vasodilation.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Ramsey IS, Delling M, Clapham DE. An introduction to TRP channels. Annu Rev Physiol. 2006;68:619–647. - PubMed
    1. Plant TD, Strotmann R. Trpv4. Handb Exp Pharmacol. 2007;(179):189–205. - PubMed
    1. Kunert-Keil C, Bisping F, Kruger J, Brinkmeier H. Tissue-specific expression of TRP channel genes in the mouse and its variation in three different mouse strains. BMC Genomics. 2006;7:159. - PMC - PubMed
    1. Nilius B, Vriens J, Prenen J, Droogmans G, Voets T. TRPV4 calcium entry channel: a paradigm for gating diversity. Am J Physiol Cell Physiol. 2004;286(2):C195–205. - PubMed
    1. Vriens J, Watanabe H, Janssens A, Droogmans G, Voets T, Nilius B. Cell swelling, heat, and chemical agonists use distinct pathways for the activation of the cation channel TRPV4. Proc Natl Acad Sci U S A. 2004;101(1):396–401. - PMC - PubMed

Publication types