Research ArticlePhysiology

AKAP150-dependent cooperative TRPV4 channel gating is central to endothelium-dependent vasodilation and is disrupted in hypertension

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Science Signaling  08 Jul 2014:
Vol. 7, Issue 333, pp. ra66
DOI: 10.1126/scisignal.2005052

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Concentrating the Signal to Relax

Regulation of blood flow involves both the endothelial cells lining the blood vessels and the surrounding smooth muscle cells, with impaired communication between these cell types leading to vascular dysfunction. Sonkusare et al. monitored endothelial cell calcium signals through single TRPV4 channels in arterial preparations from mice and found that these channels were more active at sites where the endothelial cells make intimate contact with the smooth muscle. Endothelial-dependent vasodilators, such as acetylcholine, activated TRPV4 channels only at these sites and required the colocalized scaffolding protein AKAP150. In a mouse model of hypertension, AKAP150 localization to these contact sites was lost, leading to lower TRPV4 channel activity, loss of agonist-induced activation of TRPV4 channels, and diminished vasodilation.

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