Department of Integrative Biology and Pharmacology, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
Biomolecules. 2023 Jan 14;13(1):177. doi: 10.3390/biom13010177.
The renal collecting duct is known to play a critical role in many physiological processes, including systemic water-electrolyte homeostasis, acid-base balance, and the salt sensitivity of blood pressure. ClC-K2 (ClC-Kb in humans) is a Cl-permeable channel expressed on the basolateral membrane of several segments of the renal tubule, including the collecting duct intercalated cells. ClC-Kb mutations are causative for Bartters' syndrome type 3 manifested as hypotension, urinary salt wasting, and metabolic alkalosis. However, little is known about the significance of the channel in the collecting duct with respect to the normal physiology and pathology of Bartters' syndrome. In this review, we summarize the available experimental evidence about the signaling determinants of ClC-K2 function and the regulation by systemic and local factors as well as critically discuss the recent advances in understanding the collecting-duct-specific roles of ClC-K2 in adaptations to changes in dietary Cl intake and maintaining systemic acid-base homeostasis.
肾集合管在许多生理过程中起着关键作用，包括全身水-电解质稳态、酸碱平衡以及血压的盐敏感性。ClC-K2（人类中的 ClC-Kb）是一种氯离子通透通道，表达在肾小管的几个节段的基底外侧膜上，包括集合管闰细胞。ClC-Kb 突变是导致 Bartter 综合征 3 型的原因，表现为低血压、尿盐丢失和代谢性碱中毒。然而，关于通道在集合管中的正常生理和 Bartter 综合征病理方面的意义知之甚少。在这篇综述中，我们总结了关于 ClC-K2 功能的信号决定因素以及全身和局部因素调节的现有实验证据，并批判性地讨论了最近在理解 ClC-K2 在适应饮食 Cl 摄入变化和维持全身酸碱平衡方面的集合管特异性作用方面的进展。
