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Arterioscler Thromb Vasc Biol. 2010 Apr;30(4):851-8. doi: 10.1161/ATVBAHA.109.196584. Epub 2010 Jan 21.

Functional role of vanilloid transient receptor potential 4-canonical transient receptor potential 1 complex in flow-induced Ca2+ influx.

Author information

1
Li Ka Shing Institute of Health Sciences, Chinese University of Hong Kong, Hong Kong, China.

Abstract

OBJECTIVE:

The present study is aimed at investigating the interaction of TRPV4 with TRPC1 and the functional role of such an interaction in flow-induced Ca(2+) influx. Hemodynamic blood flow is an important physiological factor that modulates vascular tone. One critical early event in this process is a cytosolic Ca(2+) ([Ca(2+)](i)) rise in endothelial cells in response to flow.

METHODS AND RESULTS:

With the use of fluorescence resonance energy transfer, coimmunoprecipitation, and subcellular colocalization methods, it was found that TRPC1 interacts physically with TRPV4 to form a complex. In functional studies, flow elicited a transient [Ca(2+)](i) increase in TRPV4-expressing human embryonic kidney (HEK) 293 cells. Coexpression of TRPC1 with TRPV4 markedly prolonged this [Ca(2+)](i) transient; it also enabled this [Ca(2+)](i) transient to be negatively modulated by protein kinase G. Furthermore, this flow-induced [Ca(2+)](i) increase was markedly inhibited by anti-TRPC1-blocking antibody T1E3 and a dominant-negative construct TRPC1 Delta 567-793 in TRPV4-C1-coexpressing HEK cells and human umbilical vein endothelial cells. T1E3 also inhibited flow-induced vascular dilation in isolated rat small mesenteric artery segments.

CONCLUSIONS:

This study shows that TRPC1 interacts physically with TRPV4 to form a complex, and this TRPV4-C1 complex may mediate flow-induced Ca(2+) influx in vascular endothelial cells. The association of TRPC1 with TRPV4 prolongs the flow-induced [Ca(2+)](i) transient, and it also enables this [Ca(2+)](i) transient to be negatively modulated by protein kinase G. This TRPV4-C1 complex plays a key role in flow-induced endothelial Ca(2+) influx.

PMID:
20093626
DOI:
10.1161/ATVBAHA.109.196584
[Indexed for MEDLINE]

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