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Differential expression patterns of K + /Cl − cotransporter 2 in neurons within the superficial spinal dorsal horn of rats
Author(s) -
Javdani Fariba,
Holló Krisztina,
Hegedűs Krisztina,
Kis Gréta,
Hegyi Zoltán,
Dócs Klaudia,
Kasugai Yu,
Fukazawa Yugo,
Shigemoto Ryuichi,
Antal Miklós
Publication year - 2015
Publication title -
journal of comparative neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.855
H-Index - 209
eISSN - 1096-9861
pISSN - 0021-9967
DOI - 10.1002/cne.23774
Subject(s) - gabaa receptor , gephyrin , glycine receptor , cotransporter , inhibitory postsynaptic potential , biology , postsynaptic potential , biophysics , receptor , microbiology and biotechnology , neuroscience , biochemistry , chemistry , glycine , amino acid , sodium , organic chemistry
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 GABA A receptors and KCC2, GABA A 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 GABA A 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 GABA A and glycine receptors along the dendrites of spinal neurons. J. Comp. Neurol. 523:1967–1983, 2015 © 2015 Wiley Periodicals, Inc.