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

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.

SUBMITTER: Sonkusare SK

PROVIDER: S-EPMC3715993 | biostudies-literature | 2012 May

REPOSITORIES: biostudies-literature

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

Sonkusare Swapnil K SK Bonev Adrian D AD Ledoux Jonathan J Liedtke Wolfgang W Kotlikoff Michael I MI Heppner Thomas J TJ Hill-Eubanks David C DC Nelson Mark T MT

Science (New York, N.Y.) 20120501 6081

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 ac ...[more]

PMID: 22556255

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

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

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