| First Author | MacKay CE | Year | 2020 |
| Journal | Elife | Volume | 9 |
| PubMed ID | 32364494 | Mgi Jnum | J:290991 |
| Mgi Id | MGI:6443502 | Doi | 10.7554/eLife.56655 |
| Citation | MacKay CE, et al. (2020) Intravascular flow stimulates PKD2 (polycystin-2) channels in endothelial cells to reduce blood pressure. Elife 9:e56655 |
| abstractText | PKD2 (polycystin-2, TRPP1), a TRP polycystin channel, is expressed in endothelial cells (ECs), but its physiological functions in this cell type are unclear. Here, we generated inducible, EC-specific Pkd2 knockout mice to examine vascular functions of PKD2. Data show that a broad range of intravascular flow rates stimulate EC PKD2 channels, producing vasodilation. Flow-mediated PKD2 channel activation leads to calcium influx that activates SK/IK channels and eNOS serine 1176 phosphorylation in ECs. These signaling mechanisms produce arterial hyperpolarization and vasodilation. In contrast, EC PKD2 channels do not contribute to acetylcholine-induced vasodilation, suggesting stimulus-specific function. EC-specific PKD2 knockout elevated blood pressure in mice without altering cardiac function or kidney anatomy. These data demonstrate that flow stimulates PKD2 channels in ECs, leading to SK/IK channel and eNOS activation, hyperpolarization, vasodilation and a reduction in systemic blood pressure. Thus, PKD2 channels are a major component of functional flow sensing in the vasculature. |
