A plasma membrane-localized polycystin-1/polycystin-2 complex in endothelial cells elicits vasodilation.

ABSTRACT: Polycystin-1 (PC-1, PKD1), a receptor-like protein expressed by the Pkd1 gene, is present in a wide variety of cell types, but its cellular location, signaling mechanisms, and physiological functions are poorly understood. Here, by studying tamoxifen-inducible, endothelial cell (EC)-specific Pkd1 knockout (Pkd1 ecKO) mice, we show that flow activates PC-1-mediated, Ca²⁺-dependent cation currents in ECs. EC-specific PC-1 knockout attenuates flow-mediated arterial hyperpolarization and vasodilation. PC-1-dependent vasodilation occurs over the entire functional shear stress range and via the activation of endothelial nitric oxide synthase (eNOS) and intermediate (IK)- and small (SK)-conductance Ca²⁺-activated K⁺ channels. EC-specific PC-1

SUBMITTER: MacKay CE 

PROVIDER: S-EPMC8933003 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature