| Autor: |
Juan Sierra-Marquez, Antje Willuweit, Michael Schöneck, Stefanie Bungert-Plümke, Jana Gehlen, Carina Balduin, Frank Müller, Angelika Lampert, Christoph Fahlke, Raul E. Guzman |
| Jazyk: |
angličtina |
| Rok vydání: |
2022 |
| Předmět: |
|
| Zdroj: |
Frontiers in Cellular Neuroscience, Vol 16 (2022) |
| Druh dokumentu: |
article |
| ISSN: |
1662-5102 |
| DOI: |
10.3389/fncel.2022.920075 |
| Popis: |
ClC-3 Cl–/H+ exchangers are expressed in multiple endosomal compartments and likely modify intra-endosomal pH and [Cl–] via the stoichiometrically coupled exchange of two Cl– ions and one H+. We studied pain perception in Clcn3–/– mice and found that ClC-3 not only modifies the electrical activity of peripheral nociceptors but is also involved in inflammatory processes in the spinal cord. We demonstrate that ClC-3 regulates the number of Nav and Kv ion channels in the plasma membrane of dorsal root ganglion (DRG) neurons and that these changes impair the age-dependent decline in excitability of sensory neurons. To distinguish the role of ClC-3 in Cl–/H+ exchange from its other functions in pain perception, we used mice homozygous for the E281Q ClC-3 point mutation (Clcn3E281Q/E281Q), which completely eliminates transport activity. Since ClC-3 forms heterodimers with ClC-4, we crossed these animals with Clcn4–/– to obtain mice completely lacking in ClC-3-associated endosomal chloride–proton transport. The electrical properties of Clcn3E281Q/E281Q/Clcn4–/– DRG neurons were similar to those of wild-type cells, indicating that the age-dependent adjustment of neuronal excitability is independent of ClC-3 transport activity. Both Clcn3–/– and Clcn3E281Q/E281Q/Clcn4–/– animals exhibited microglial activation in the spinal cord, demonstrating that competent ClC-3 transport is needed to maintain glial cell homeostasis. Our findings illustrate how reduced Cl–/H+ exchange contributes to inflammatory responses and demonstrate a role for ClC-3 in the homeostatic regulation of neuronal excitability beyond its function in endosomal ion balance. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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