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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Sonkusare, SK; Bonev, AD; Ledoux, J; Liedtke, W; Kotlikoff, MI; Heppner, TJ; Hill-Eubanks, DC; Nelson, MT

Published Date

  • May 4, 2012

Published In

Volume / Issue

  • 336 / 6081

Start / End Page

  • 597 - 601

PubMed ID

  • 22556255

Pubmed Central ID

  • 22556255

Electronic International Standard Serial Number (EISSN)

  • 1095-9203

Digital Object Identifier (DOI)

  • 10.1126/science.1216283

Language

  • eng

Conference Location

  • United States