Nephrology Research Group, Department of Medicine, Laval University, 11, côte du Palais, Québec (Qc), Canada, G1R 2J6.
Cardiometabolic Axis, School of Kinesiology and Physical Activity Sciences, Montreal University, 900, rue Saint-Denis, Montréal, (Qc) H2X 0A9.
J Physiol. 2019 Mar;597(6):1451-1465. doi: 10.1113/JP276807. Epub 2019 Feb 9.
In the early 80s, renal microperfusion studies led to the identification of a basolateral K -Cl cotransport mechanism in the proximal tubule, thick ascending limb of Henle and collecting duct. More than ten years later, this mechanism was found to be accounted for by three different K -Cl cotransporters (KCC1, KCC3 and KCC4) that are differentially distributed along the renal epithelium. Two of these isoforms (KCC1 and KCC3) were also found to be expressed in arterial walls, the myocardium and a variety of neurons. Subsequently, valuable insights have been gained into the molecular and physiological properties of the KCCs in both the mammalian kidney and cardiovascular system. There is now robust evidence indicating that KCC4 sustains distal renal acidification and that KCC3 regulates myogenic tone in resistance vessels. However, progress in understanding the functional significance of these transporters has been slow, probably because each of the KCC isoforms is not identically distributed among species and some of them share common subcellular localizations with other KCC isoforms or sizeable conductive Cl pathways. In addition, the mechanisms underlying the process of K -Cl cotransport are still ill defined. The present review focuses on the knowledge gained regarding the roles and properties of KCCs in renal and cardiovascular tissues.
80 年代初，肾脏微灌注研究导致人们在近端小管、亨利氏袢升支粗段和集合管中鉴定出基底外侧 K-Cl 共转运机制。十多年后，人们发现该机制由三种不同的 K-Cl 共转运体（KCC1、KCC3 和 KCC4）介导，它们在肾上皮细胞中呈不同分布。这两种同工型（KCC1 和 KCC3）也在动脉壁、心肌和各种神经元中表达。随后，人们对哺乳动物肾脏和心血管系统中 KCC 的分子和生理特性有了宝贵的认识。现在有强有力的证据表明 KCC4 维持远端肾脏酸化，而 KCC3 调节阻力血管的肌源性紧张。然而，对这些转运体的功能意义的理解进展缓慢，可能是因为每种 KCC 同工型在物种间的分布并不完全相同，其中一些同工型与其他 KCC 同工型或相当大的导电 Cl 途径具有共同的亚细胞定位。此外，K-Cl 共转运的机制仍未明确界定。本文综述了关于 KCC 在肾脏和心血管组织中的作用和特性的研究进展。
