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  • Intravascular flow stimulates PKD2 (polycystin-2) channels in endothelial cells to reduce blood pressure.

Intravascular flow stimulates PKD2 (polycystin-2) channels in endothelial cells to reduce blood pressure.

eLife (2020-05-05)
Charles E MacKay, M Dennis Leo, Carlos Fernández-Peña, Raquibul Hasan, Wen Yin, Alejandro Mata-Daboin, Simon Bulley, Jesse Gammons, Salvatore Mancarella, Jonathan H Jaggar
ABSTRACT

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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-Trpv4 Antibody, clone 1B2.6, clone 1B2.6, from mouse
Sigma-Aldrich
Anti-Actin Antibody, clone C4, ascites fluid, clone C4, Chemicon®