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Review
. 2014 Sep;29(5):343-60.
doi: 10.1152/physiol.00009.2014.

Vascular TRP channels: performing under pressure and going with the flow

David C Hill-Eubanks  1 , Albert L Gonzales  1 , Swapnil K Sonkusare  1 , Mark T Nelson  2
Affiliations
Review

Vascular TRP channels: performing under pressure and going with the flow

David C Hill-Eubanks et al. Physiology (Bethesda). 2014 Sep.

Abstract

Endothelial cells and smooth muscle cells of resistance arteries mediate opposing responses to mechanical forces acting on the vasculature, promoting dilation in response to flow and constriction in response to pressure, respectively. In this review, we explore the role of TRP channels, particularly endothelial TRPV4 and smooth muscle TRPC6 and TRPM4 channels, in vascular mechanosensing circuits, placing their putative mechanosensitivity in context with other proposed upstream and downstream signaling pathways.

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Conflict of interest statement

No conflicts of interest, financial or otherwise, are declared by the author(s).

Figures

FIGURE 1.
FIGURE 1.
Forces acting within blood vessels Blood flowing through an arterial segment induces hemodynamic forces that can be categorized into two principle components: 1) a force perpendicular to the vessel wall, defined as tensile stress, representing the force due to blood pressure (P), which is proportional to cardiac output resistance, and 2) a force parallel to the vessel wall, defined as shear stress (τ), corresponding to the frictional force exerted on the vessel wall. END, endothelium; IEL, internal elastic lamina; SM, smooth muscle.
FIGURE 2.
FIGURE 2.
Flow-induced TRPV4 sparklets in resistance-sized mesenteric arteries Endothelial cells in an en face preparation of resistance-size mesenteric arteries from GCaMP mice were stimulated by a brief, parallel-oriented flow of bath solution delivered by picospritzing (pressure, 1.5 bar; tip diameter, 5–6 μ m; distance from surface, ∼20 μ m). Ca2+ signals were imaged by confocal microscopy. Picospritzing-induced Ca2+ signals were largely abolished by the TRPV4 antagonist HC067047, establishing their identity as TRPV4-mediated events. Top: representative raw trace. Bottom: summary data (n = 3 fields from 3 arteries) (previously unpublished data).
FIGURE 3.
FIGURE 3.
Possible mechanisms of flow-induced TRPV4 activation Blood flow through the vessel lumen exerts frictional forces on to the endothelial membrane that could activate TRPV4 directly via membrane deformation, indirectly through a biochemical conversion mechanism involving upstream signaling elements (e.g., GPCRs, PLA2), or through a lever-like action involving cytoskeletal linkages to molecules embedded in the glycocalyx. In addition to acting on TRPV4 channels on the apical surface, this mechanism could indirectly engage TRPV4 channels within MEP microdomains (inset) on the basal surface to induce endothelial-dependent vasodilation through an SK/IK channel-dependent EDH mechanism or do so indirectly through a Ca2+-induced Ca2+-release mechanism involving an internal IP3R-mediated signaling cascade. Alternatively, the TRPV4-mediated rise in intracellular Ca2+ might act via eNOS-mediated production of NO or elaboration of PGI2 through COX action on PLA2-derived AA. Although pictured as a single channel, TRPV4 channels most likely function in the cells as a four-channel metastructure.
FIGURE 4.
FIGURE 4.
Smooth muscle contraction through pressure-dependent activation of TRPM4 and TRPC6 Stretch of the plasma membrane (PM) activates GPCRs, stimulating PLC and generation of the second messengers DAG and IP3, which act through parallel pathways that converge on the IP3R, DAG activates TRPC6, and the subsequent influx of Ca2+ sensitizes IP3Rs to co-produced IP3, initiating Ca2+-induced Ca2+ release and activation of TRPM4. Currents through TRPC6 and TRPM4 depolarize the plasma membrane, activating VDCCs and leading to smooth muscle contraction.
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References

    1. AbouAlaiwi WA, Takahashi M, Mell BR, Jones TJ, Ratnam S, Kolb RJ, Nauli SM. Ciliary polycystin-2 is a mechanosensitive calcium channel involved in nitric oxide signaling cascades. Circ Res 104: 860–869, 2009 - PMC - PubMed
    1. Albert AP, Saleh SN, Large WA. Inhibition of native TRPC6 channel activity by phosphatidylinositol 4,5-bisphosphate in mesenteric artery myocytes. J Physiol 586: 3087–3095, 2008 - PMC - PubMed
    1. Andresen J, Shafi NI, Bryan RM, Jr. Endothelial influences on cerebrovascular tone. J Appl Physiol 100: 318–327, 2006 - PubMed
    1. Bagher P, Beleznai T, Kansui Y, Mitchell R, Garland CJ, Dora KA. Low intravascular pressure activates endothelial cell TRPV4 channels, local Ca2+ events, and IKCa channels, reducing arteriolar tone. Proc Natl Acad Sci USA 109: 18174–18179, 2012 - PMC - PubMed
    1. Bagi Z, Koller A. Lack of nitric oxide mediation of flow-dependent arteriolar dilation in type I diabetes is restored by sepiapterin. J Vasc Res 40: 47–57, 2003 - PubMed

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