Charité University Medicine, Section Nephrology/Intensive Care, Campus Virchow, and Experimental and Clinical Research Center (ECRC), Berlin, Germany.
Acta Physiol (Oxf). 2013 Mar;207(3):546-64. doi: 10.1111/apha.12051. Epub 2013 Jan 18.
Recent preclinical data indicate that activators of transient receptor potential channels of the vanilloid receptor subtype 1 (TRPV1) may improve the outcome of ischaemic acute kidney injury (AKI). The underlying mechanisms are unclear, but may involve TRPV1 channels in dorsal root ganglion neurones that innervate the kidney. Recent data identified TRPV4, together with TRPV1, to serve as major calcium influx channels in endothelial cells. In these cells, gating of individual TRPV4 channels within a four-channel cluster provides elementary calcium influx (calcium sparklets) to open calcium-activated potassium channels and promote vasodilation. The TRPV receptors can also form heteromers that exhibit unique conductance and gating properties, further increasing their spatio-functional diversity. This review summarizes data on electrophysiological properties of TRPV1/4 and their modulation by endogenous channel agonists such as 20-HETE, phospholipase C and phosphatidylinositide 3-kinase (PI3 kinase). We review important roles of TRPV1 and TRPV4 in kidney physiology and renal ischaemia reperfusion injury; further studies are warranted to address renoprotective mechanism of vanilloid receptors in ischaemic AKI including the role of the capsaicin receptor TRPV1 in primary sensory nerves and/or endothelium. Particular attention should be paid to understand the kidneys' ability to respond to ischaemic stimuli after catheter-based renal denervation therapy in man, whereas the discovery of novel pharmacological TRPV modulators may be a successful strategy for better treatment of acute or chronic kidney failure.
最近的临床前数据表明，辣椒素受体亚型 1（TRPV1）瞬时受体电位通道激活剂可能改善缺血性急性肾损伤（AKI）的预后。其潜在机制尚不清楚，但可能涉及支配肾脏的背根神经节神经元中的 TRPV1 通道。最近的数据确定 TRPV4 与 TRPV1 一起作为内皮细胞中的主要钙内流通道。在这些细胞中，四通道簇内单个 TRPV4 通道的门控提供基本的钙内流（钙火花）以打开钙激活的钾通道并促进血管舒张。TRPV 受体还可以形成异二聚体，表现出独特的电导和门控特性，进一步增加其时空功能多样性。这篇综述总结了 TRPV1/4 的电生理特性及其被内源性通道激动剂（如 20-HETE、磷脂酶 C 和磷脂酰肌醇 3-激酶（PI3 激酶））调节的数据。我们综述了 TRPV1 和 TRPV4 在肾脏生理学和肾缺血再灌注损伤中的重要作用；需要进一步的研究来解决辣椒素受体在缺血性 AKI 中的肾保护机制，包括辣椒素受体 TRPV1 在初级感觉神经和/或内皮中的作用。特别需要注意的是，要了解人类基于导管的肾脏去神经治疗后肾脏对缺血刺激的反应能力，而发现新型药理学 TRPV 调节剂可能是治疗急性或慢性肾衰竭的成功策略。
