Referenced in: none

Automatically associated channels: TRP , TRPV , TRPV4

Title: Elementary Ca2+ signals through endothelial TRPV4 channels regulate vascular function.

Authors: Swapnil K Sonkusare, Adrian D Bonev, Jonathan Ledoux, Wolfgang Liedtke, Michael I Kotlikoff, Thomas J Heppner, David C Hill-Eubanks, Mark T Nelson

Journal, date & volume: Science, 2012 May 4 , 336, 597-601

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/22556255

Abstract
Major features of the transcellular signaling mechanism responsible for endothelium-dependent regulation of vascular smooth muscle tone are unresolved. We identified local calcium (Ca(2+)) signals ("sparklets") in the vascular endothelium of resistance arteries that represent Ca(2+) influx through single TRPV4 cation channels. Gating of individual TRPV4 channels within a four-channel cluster was cooperative, with activation of as few as three channels per cell causing maximal dilation through activation of endothelial cell intermediate (IK)- and small (SK)-conductance, Ca(2+)-sensitive potassium (K(+)) channels. Endothelial-dependent muscarinic receptor signaling also acted largely through TRPV4 sparklet-mediated stimulation of IK and SK channels to promote vasodilation. These results support the concept that Ca(2+) influx through single TRPV4 channels is leveraged by the amplifier effect of cooperative channel gating and the high Ca(2+) sensitivity of IK and SK channels to cause vasodilation.