Elementary Ca2+ signals through endothelial TRPV4 channels regulate vascular function.
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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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
Citation
Published In
DOI
EISSN
Publication Date
Volume
Issue
Start / End Page
Location
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