title: KCC3-dependent chloride extrusion in adult sensory neurons.
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.
authors.affiliation: Inserm, U-1051, Institute for Neurosciences of Montpellier, Montpellier, F-34000, 80, rue Augustin Fliche, 34091 Montpellier Cedex 5, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Lucas
authors.forename: Cécile
authors.initials: C
authors.lastname: Hilaire
authors.forename: Eric
authors.initials: E
authors.lastname: Delpire
authors.forename: Frédérique
authors.initials: F
authors.lastname: Scamps
mesh_terms: D000818:Animals; D001693:Biological Transport, Active / Q000235:genetics; D002712:Chlorides / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018408:Patch-Clamp Techniques; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D011984:Sensory Receptor Cells / Q000378:metabolism*; D028021:Sodium-Potassium-Chloride Symporters / Q000378:metabolism; D064506:Solute Carrier Family 12, Member 2; D027981:Symporters / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D000096922:K Cl- Cotransporters
chemical_list: D002712:Chlorides; D020033:Protein Isoforms; D028021:Sodium-Potassium-Chloride Symporters; D064506:Solute Carrier Family 12, Member 2; D027981:Symporters; D000096922:K Cl- Cotransporters; C578878:Slc12a2 protein, mouse; C492280:Slc12a6 protein, mouse