Molecular insights into the normal operation, regulation, and multisystemic roles of K + -Cl − cotransporter 3 (KCC3)

The Journal of Physiology

et al. 2019

Self Cite

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.

Section: Introductionmentioning

confidence: 99%

“…Each of the KCC genes can be processed into several splice variants (Garneau et al . ; Marcoux et al . ).…”

Section: Introductionmentioning

confidence: 99%

“…The mRNA sequences are designated according to the nomenclature of GenBank and to that of previous reviews (Garneau et al . ; Marcoux et al . ).…”

Section: Introductionmentioning

confidence: 99%

“…Among the various CCCs, importantly, the central domain and C‐terminus are more conserved than the N‐terminus (Garneau et al . ; Marcoux et al . ).…”

Section: Introductionmentioning

confidence: 99%

“…The topological configuration of the KCCs is predicted to be nearly identical to that of NKCC1, NKCC2 and NCC (Garneau et al . ; Marcoux et al . ), i.e.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Physiological roles and molecular mechanisms of K⁺‐Cl⁻ cotransport in the mammalian kidney and cardiovascular system: where are we?

Garneau

Marcoux

The Journal of Physiology

et al. 2019

Self Cite

Molecular characteristics and physiological roles of Na⁺–K⁺–Cl⁻ cotransporter 2

Marcoux

Tremblay

Journal Cellular Physiology

et al. 2020

Na +-K +-Cl − cotransporter 2 (NKCC2; SLC12A1) is an integral membrane protein that comes as three splice variants and mediates the cotranslocation of Na + , K + , and Cl − ions through the apical membrane of the thick ascending loop of Henle (TALH). In doing so, and through the involvement of other ion transport systems, it allows this nephron segment to reclaim a large fraction of the ultrafiltered Na + , Cl − , Ca 2+ , Mg 2+ , and HCO 3 − loads. The functional relevance of NKCC2 in human is illustrated by the many abnormalities that result from the inactivation of this transport system through the use of loop diuretics or in the setting of inherited disorders. The following presentation aims at discussing the physiological roles and molecular characteristics of Na +-K +-Cl − cotransport in the TALH and those of the individual NKCC2 splice variants more specifically. Many of the historical and recent data that have emerged from the experiments conducted will be outlined and their larger meaning will also be placed into perspective with the aid of various hypotheses.

Molecular mechanisms, physiological roles, and therapeutic implications of ion fluxes in bone cells: Emphasis on the cation‐Cl⁻ cotransporters

Garneau

Journal Cellular Physiology

Haydock

et al. 2022

Bone turnover diseases are exceptionally prevalent in human and come with a high burden on physical health. While these diseases are associated with a variety of risk factors and causes, they are all characterized by common denominators, that is, abnormalities in the function or number of osteoblasts, osteoclasts, and/or osteocytes. As such, much effort has been deployed in the recent years to understand the signaling mechanisms of bone cell proliferation and differentiation with the objectives of exploiting the intermediates involved as therapeutic preys. Ion transport systems at the external and in the intracellular membranes of osteoblasts and osteoclasts also play an important role in bone turnover by coordinating the movement of Ca2+, PO42−, and H+ ions in and out of the osseous matrix. Even if they sustain the terminal steps of osteoformation and osteoresorption, they have been the object of very little attention in the last several years. Members of the cation‐Cl− cotransporter (CCC) family are among the systems at work as they are expressed in bone cells, are known to affect the activity of Ca2+‐, PO42−‐, and H+‐dependent transport systems and have been linked to bone mass density variation in human. In this review, the roles played by the CCCs in bone remodeling will be discussed in light of recent developments and their potential relevance in the treatment of skeletal disorders.