Elementary Ca2+ signals through endothelial TRPV4 channels regulate vascular function.
Journal Article (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
- PMC3715993
Electronic International Standard Serial Number (EISSN)
- 1095-9203
Digital Object Identifier (DOI)
- 10.1126/science.1216283
Language
- eng
Conference Location
- United States