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

Publication ,  Journal Article
Sonkusare, SK; Bonev, AD; Ledoux, J; Liedtke, W; Kotlikoff, MI; Heppner, TJ; Hill-Eubanks, DC; Nelson, MT
Published in: Science
May 4, 2012

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.

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Published In

Science

DOI

EISSN

1095-9203

Publication Date

May 4, 2012

Volume

336

Issue

6081

Start / End Page

597 / 601

Location

United States

Related Subject Headings

  • Vasodilation
  • TRPV Cation Channels
  • Sulfonamides
  • Small-Conductance Calcium-Activated Potassium Channels
  • Signal Transduction
  • Receptors, Muscarinic
  • Patch-Clamp Techniques
  • Mice, Transgenic
  • Mice, Inbred C57BL
  • Mice
 

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Sonkusare, S. K., Bonev, A. D., Ledoux, J., Liedtke, W., Kotlikoff, M. I., Heppner, T. J., … Nelson, M. T. (2012). Elementary Ca2+ signals through endothelial TRPV4 channels regulate vascular function. Science, 336(6081), 597–601. https://doi.org/10.1126/science.1216283
Sonkusare, Swapnil K., Adrian D. Bonev, Jonathan Ledoux, Wolfgang Liedtke, Michael I. Kotlikoff, Thomas J. Heppner, David C. Hill-Eubanks, and Mark T. Nelson. “Elementary Ca2+ signals through endothelial TRPV4 channels regulate vascular function.Science 336, no. 6081 (May 4, 2012): 597–601. https://doi.org/10.1126/science.1216283.
Sonkusare SK, Bonev AD, Ledoux J, Liedtke W, Kotlikoff MI, Heppner TJ, et al. Elementary Ca2+ signals through endothelial TRPV4 channels regulate vascular function. Science. 2012 May 4;336(6081):597–601.
Sonkusare, Swapnil K., et al. “Elementary Ca2+ signals through endothelial TRPV4 channels regulate vascular function.Science, vol. 336, no. 6081, May 2012, pp. 597–601. Pubmed, doi:10.1126/science.1216283.
Sonkusare SK, Bonev AD, Ledoux J, Liedtke W, Kotlikoff MI, Heppner TJ, Hill-Eubanks DC, Nelson MT. Elementary Ca2+ signals through endothelial TRPV4 channels regulate vascular function. Science. 2012 May 4;336(6081):597–601.
Journal cover image

Published In

Science

DOI

EISSN

1095-9203

Publication Date

May 4, 2012

Volume

336

Issue

6081

Start / End Page

597 / 601

Location

United States

Related Subject Headings

  • Vasodilation
  • TRPV Cation Channels
  • Sulfonamides
  • Small-Conductance Calcium-Activated Potassium Channels
  • Signal Transduction
  • Receptors, Muscarinic
  • Patch-Clamp Techniques
  • Mice, Transgenic
  • Mice, Inbred C57BL
  • Mice