Differential expression patterns of K+Cl- cotransporter 2 in neurons within the superficial spinal dorsal horn of rats Journal Article


Author(s): Javdani, Fariba; Holló, Krisztina; Hegedűs, Krisztina; Kis, Gréta; Hegyi, Zoltán; Dócs, Klaudia; Kasugai, Yu; Fukazawa, Yugo; Shigemoto, Ryuichi; Antal, Miklós
Article Title: Differential expression patterns of K+Cl- cotransporter 2 in neurons within the superficial spinal dorsal horn of rats
Affiliation IST Austria
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.
Keywords: AB_1587626; AB_2263126; AB_518152; Cation-chloride cotransporters; Gephyrin; Nif-0000-00110; Nif-0000-00314; Nif-0000-10267; NK1 receptor-immunoreactive neurons; Nlx_156277; RRID:AB_2232546; RRID:AB_2278725; RRID:AB_992894; RRIDs:AB_310611; SciRes_000161; Spinal dorsal horn; β3 subunit of GABAA receptors
Journal Title: Journal of Comparative Neurology
Volume: 523
Issue 13
ISSN: 0021-9967
Publisher: Wiley-Blackwell  
Date Published: 2015-09-01
Start Page: 1967
End Page: 1983
DOI: 10.1002/cne.23774
Notes: Funded by: Hungarian Academy of Sciences. Grant Number: MTA-TKI 242 Hungarian Brain Research Program. Grant Number: KTIA_NAP_13-1-2013-0001 Solution Oriented Research for Science and Technology from the Japan Science and Technology Agency Japanese Ministry of Education, Culture, Sports, Science and Technology
Open access: no