title: Differential expression patterns of K(+) /Cl(-) cotransporter 2 in neurons within the superficial spinal dorsal horn of rats.
abstract: γ-Aminobutyric acid (GABA)- and glycine-mediated hyperpolarizing inhibition is associated with a chloride influx that depends on the inwardly directed chloride electrochemical gradient. In neurons, the extrusion of chloride from the cytosol primarily depends on the expression of an isoform of potassium-chloride cotransporters (KCC2s). KCC2 is crucial in the regulation of the inhibitory tone of neural circuits, including pain processing neural assemblies. Thus we investigated the cellular distribution of KCC2 in neurons underlying pain processing in the superficial spinal dorsal horn of rats by using high-resolution immunocytochemical methods. We demonstrated that perikarya and dendrites widely expressed KCC2, but axon terminals proved to be negative for KCC2. In single ultrathin sections, silver deposits labeling KCC2 molecules showed different densities on the surface of dendritic profiles, some of which were negative for KCC2. In freeze fracture replicas and tissue sections double stained for the β3-subunit of GABAA receptors and KCC2, GABAA receptors were revealed on dendritic segments with high and also with low KCC2 densities. By measuring the distances between spots immunoreactive for gephyrin (a scaffolding protein of GABAA and glycine receptors) and KCC2 on the surface of neurokinin 1 (NK1) receptor-immunoreactive dendrites, we found that gephyrin-immunoreactive spots were located at various distances from KCC2 cotransporters; 5.7 % of them were recovered in the middle of 4-10-µm-long dendritic segments that were free of KCC2 immunostaining. The variable local densities of KCC2 may result in variable postsynaptic potentials evoked by the activation of GABAA and glycine receptors along the dendrites of spinal neurons.
authors.affiliation: Department of Anatomy, Histology and Embryology, Faculty of Medicine, University of Debrecen, Debrecen 4012, Hungary.
authors.forename: Fariba
authors.initials: F
authors.lastname: Javdani
authors.affiliation: Department of Anatomy, Histology and Embryology, Faculty of Medicine, University of Debrecen, Debrecen 4012, Hungary.
authors.forename: Krisztina
authors.initials: K
authors.lastname: Holló
authors.affiliation: Department of Anatomy, Histology and Embryology, Faculty of Medicine, University of Debrecen, Debrecen 4012, Hungary.
authors.forename: Krisztina
authors.initials: K
authors.lastname: Hegedűs
authors.affiliation: Department of Anatomy, Histology and Embryology, Faculty of Medicine, University of Debrecen, Debrecen 4012, Hungary.
authors.forename: Gréta
authors.initials: G
authors.lastname: Kis
authors.affiliation: Department of Anatomy, Histology and Embryology, Faculty of Medicine, University of Debrecen, Debrecen 4012, Hungary.
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Hegyi
authors.affiliation: Department of Anatomy, Histology and Embryology, Faculty of Medicine, University of Debrecen, Debrecen 4012, Hungary.
authors.forename: Klaudia
authors.initials: K
authors.lastname: Dócs
authors.affiliation: Department of Pharmacology, Innsbruck Medical University, Innsbruck 6020, Austria.
authors.forename: Yu
authors.initials: Y
authors.lastname: Kasugai
authors.affiliation: Division of Cell Biology and Neuroscience, Faculty of Medical Sciences, University of Fukui, Yoshida, 910-1193, Japan.
authors.forename: Yugo
authors.initials: Y
authors.lastname: Fukazawa
authors.affiliation: Institute of Science and Technology Austria, Klosterneuburg, 3400, Austria.
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Shigemoto
authors.affiliation: Department of Anatomy, Histology and Embryology, Faculty of Medicine, University of Debrecen, Debrecen 4012, Hungary.|MTA-DE Neuroscience Research Group, Debrecen, 4012, Hungary.
authors.forename: Miklós
authors.initials: M
authors.lastname: Antal
mesh_terms: D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D005968:Glutamate Decarboxylase / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D016253:Microscopy, Immunoelectron; D020671:Posterior Horn Cells / Q000166:cytology / Q000000981:diagnostic imaging / Q000378:metabolism*; D017729:Presynaptic Terminals / Q000378:metabolism / Q000648:ultrastructure; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000378:metabolism; D018040:Receptors, Neurokinin-1 / Q000378:metabolism; D066148:Spinal Cord Dorsal Horn / Q000166:cytology*; D027981:Symporters / Q000378:metabolism*; D014463:Ultrasonography; D050599:Vesicular Glutamate Transport Protein 2 / Q000378:metabolism / Q000648:ultrastructure; D000096922:K Cl- Cotransporters
chemical_list: D015740:Calcitonin Gene-Related Peptide; D002352:Carrier Proteins; D005968:Glutamate Decarboxylase; D008565:Membrane Proteins; D011963:Receptors, GABA-A; D018040:Receptors, Neurokinin-1; D027981:Symporters; D050599:Vesicular Glutamate Transport Protein 2; D000096922:K Cl- Cotransporters; C493475:Slc17a6 protein, rat; C073441:gephyrin; C402565:glutamate decarboxylase 1; C401141:glutamate decarboxylase 2
keywords: AB_1587626; AB_2263126; AB_518152; NK1 receptor-immunoreactive neurons; RRID:AB_2232546; RRID:AB_2278725; RRID:AB_992894; RRIDs:AB_310611; SciRes_000161; cation-chloride cotransporters; gephyrin; nif-0000-00110; nif-0000-00314; nif-0000-10267; nlx_156277; spinal dorsal horn; β3 subunit of GABAA receptors