Department of Physiology University of Tennessee Health Science Center Memphis, Memphis, United States.
Elife. 2020 May 4;9:e56655. doi: 10.7554/eLife.56655.
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 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.
PKD2（多囊蛋白 2，TRPP1）是一种 TRP 多囊蛋白通道，在血管内皮细胞（ECs）中表达，但在这种细胞类型中的生理功能尚不清楚。在这里，我们生成了诱导型、内皮细胞特异性 PKD2 敲除小鼠，以研究 PKD2 在血管中的功能。数据表明，广泛的血管内血流速率刺激 EC PKD2 通道，引起血管舒张。血流介导的 PKD2 通道激活导致钙内流，激活 SK/IK 通道和 ECs 中 eNOS 丝氨酸 1176 磷酸化。这些信号转导机制产生动脉超极化和血管舒张。相比之下，EC PKD2 通道不参与乙酰胆碱诱导的血管舒张，表明其具有刺激特异性功能。内皮细胞特异性 PKD2 敲除导致小鼠血压升高，而不改变心脏功能或肾脏解剖结构。这些数据表明，血流刺激 ECs 中的 PKD2 通道，导致 SK/IK 通道和 eNOS 激活、超极化、血管舒张以及全身血压降低。因此，PKD2 通道是血管中功能性血流感应的主要组成部分。
