1. KCC3-dependent chloride extrusion in adult sensory neurons.
- Author
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Lucas O, Hilaire C, Delpire E, and Scamps F
- Subjects
- Animals, Biological Transport, Active genetics, Gene Expression Regulation, Developmental, Mice, Mice, Inbred C57BL, Mice, Knockout, Patch-Clamp Techniques, Protein Isoforms genetics, Protein Isoforms metabolism, Sodium-Potassium-Chloride Symporters metabolism, Solute Carrier Family 12, Member 2, Symporters genetics, Transcription, Genetic, K Cl- Cotransporters, Chlorides metabolism, Sensory Receptor Cells metabolism, Symporters metabolism
- Abstract
The cation-Cl(-) cotransporters participate to neuronal Cl(-) balance and are responsible for the post-natal Cl(-) switch in central neurons. In the adult peripheral nervous system, it is not well established whether a Cl(-) transition occurs during maturation. We investigated the contribution of cation-Cl(-) cotransporters in the Cl(-) handling of sensory neurons derived from the dorsal root ganglia (DRG) of neonatal mice (postnatal days 1-6) and adult mice. Gramicidin-perforated patch-clamp recordings in wild-type neurons revealed that Cl(-) accumulated to very high values in P1-6 sensory neurons and decreased in adulthood. In post-natal sensory neurons, quantitative RT-PCR showed that NKCC1, KCC1 and KCC3 had a higher transcript expression level compared to KCC2 and KCC4. NKCC1 was the main cation-Cl(-) cotransporter controlling Cl(-) accumulation at this developmental stage. In adulthood, the KCC3 transcript was produced in larger amounts than the other cation-Cl(-) cotransporter transcripts and RT-PCR shows larger expression of the shorter KCC3a isoform in adult DRG. Pharmacological inhibitors of cation-Cl(-) cotransporters and the use of KCC3(-/-) mice demonstrated that NKCC1 sustained Cl(-) accumulation in the majority of adult sensory neurons while KCC3 contributed to Cl(-) extrusion in a subset of these neurons. Beta-galactosidase detection in adult KCC3(-/-) DRG showed that KCC3 transcripts were present in all adult sensory neurons suggesting a KCC3 isoform specific regulation of Cl(-) handling. The contribution of KCC3 to Cl(-) extrusion in a subset of sensory neurons indicates that KCC3 could play a major role in GABAergic/glycinergic transmission., (Copyright © 2012 Elsevier Inc. All rights reserved.)
- Published
- 2012
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