Physiological roles of chloride ions in bodily and cellular functions

Abstract

Physiological roles of Cl−, a major anion in the body, are not well known compared with those of cations. This review article introduces: (1) roles of Cl− in bodily and cellular functions; (2) the range of cytosolic Cl− concentration ([Cl−]c); (3) whether [Cl−]c could change with cell volume change under an isosmotic condition; (4) whether [Cl−]c could change under conditions where multiple Cl− transporters and channels contribute to Cl− influx and efflux in an isosmotic state; (5) whether the change in [Cl−]c could be large enough to act as signals; (6) effects of Cl− on cytoskeletal tubulin polymerization through inhibition of GTPase activity and tubulin polymerization-dependent biological activity; (7) roles of cytosolic Cl− in cell proliferation; (8) Cl−-regulatory mechanisms of ciliary motility; (9) roles of Cl− in sweet/umami taste receptors; (10) Cl−-regulatory mechanisms of with-no-lysine kinase (WNK); (11) roles of Cl− in regulation of epithelial Na+ transport; (12) relationship between roles of Cl− and H+ in body functions.

The Role of Ion-Transporting Proteins in Human Disease

“…Currently, four modulators have been approved by drug regulatory agencies in Europe and the USA, and the indication for each therapeutic agent depends on the specific CFTR genetic variants present [18]. Further, Cl − channels play a variety of important roles in bodily and cellular functions, such as regulation of cell volume [19,20] (Figure 2) and cell migration [21] (Figure 3). NKCC1 is involved in uptake into the cytosolic space with Na + and K + [22][23][24][25][26].…”

“…The uptake of these ions results in an influx of water into the cytosolic space via AQP due to an increase in cytosolic osmolarity [22]. The movement of Cl − , Na + , K + and water causes an increase in cell volume accompanied by [Cl − ] c elevation, which promotes tubulin polymerization (elongation) [27] by inhibiting GTPase activity [21]. Like tubulin polymerization, actin monomers are enhanced to be polymerized.…”

“…AQP-mediated water efflux to the extracellular space is caused by diminution in cytosolic osmolarity due to excretion of these ions. The movement of Cl − , K + and water results in a decrease in cell volume accompanied by [Cl − ] c diminution, which leads to tubulin depolymerization (shortening) during the tail-end of the cell migration [27] by activating GTPase [21]. WNK activated by lowered [Cl − ] c induces phosphorylation (activation) of OSR1/SPACK, which increases NKCC1 activity by phosphorylating NKCC1 [23].…”

“…Thus, WNK is crucial within cell migration [23]. This figure has been published in an article by Marunaka [21] and is described under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/) on 16 January 2024.…”