| First Author | Khavandi K | Year | 2016 |
| Journal | Sci Signal | Volume | 9 |
| Issue | 449 | Pages | ra100 |
| PubMed ID | 27729550 | Mgi Jnum | J:260395 |
| Mgi Id | MGI:6141544 | Doi | 10.1126/scisignal.aaf6625 |
| Citation | Khavandi K, et al. (2016) Pressure-induced oxidative activation of PKG enables vasoregulation by Ca2+ sparks and BK channels. Sci Signal 9(449):ra100 |
| abstractText | Activation of Ca(2+)-sensitive, large-conductance potassium (BK) channels in vascular smooth muscle cells (VSMCs) by local, ryanodine receptor-mediated Ca(2+) signals (Ca(2+) sparks) acts as a brake on pressure-induced (myogenic) vasoconstriction-a fundamental mechanism that regulates blood flow in small resistance arteries. We report that physiological intraluminal pressure within resistance arteries activated cGMP-dependent protein kinase (PKG) in VSMCs through oxidant-induced formation of an intermolecular disulfide bond between cysteine residues. Oxidant-activated PKG was required to trigger Ca(2+) sparks, BK channel activity, and vasodilation in response to pressure. VSMCs from arteries from mice expressing a form of PKG that could not be activated by oxidants showed reduced Ca(2+) spark frequency, and arterial preparations from these mice had decreased pressure-induced activation of BK channels. Thus, the absence of oxidative activation of PKG disabled the BK channel-mediated negative feedback regulation of vasoconstriction. Our results support the concept of a negative feedback control mechanism that regulates arterial diameter through mechanosensitive production of oxidants to activate PKG and enhance Ca(2+) sparks. |
