| First Author | Sonkusare SK | Year | 2012 |
| Journal | Science | Volume | 336 |
| Issue | 6081 | Pages | 597-601 |
| PubMed ID | 22556255 | Mgi Jnum | J:317223 |
| Mgi Id | MGI:6839880 | Doi | 10.1126/science.1216283 |
| Citation | Sonkusare SK, et al. (2012) Elementary Ca2+ signals through endothelial TRPV4 channels regulate vascular function. Science 336(6081):597-601 |
| abstractText | 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. |
