title: Kv4.2 potassium channels segregate to extrasynaptic domains and influence intrasynaptic NMDA receptor NR2B subunit expression.
abstract: Neurons of the intercalated cell clusters (ITCs) represent an important relay site for information flow within amygdala nuclei. These neurons receive mainly glutamatergic inputs from the basolateral amygdala at their dendritic domains and provide feed-forward inhibition to the central nucleus. Voltage-gated potassium channels type-4.2 (Kv4.2) are main players in dendritic signal processing and integration providing a key component of the A currents. In this study, the subcellular localization and distribution of the Kv4.2 was studied in ITC neurons by means of light- and electron microscopy, and compared to other types of central principal neurons. Several ultrastructural immunolocalization techniques were applied including pre-embedding techniques and, most importantly, SDS-digested freeze-fracture replica labeling. We found Kv4.2 densely expressed in somato-dendritic domains of ITC neurons where they show a differential distribution pattern as revealed by nearest neighbor analysis. Comparing ITC neurons with hippocampal pyramidal and cerebellar granule cells, a cell type- and domain-dependent organization in Kv4.2 distribution was observed. Kv4.2 subunits were localized to extrasynaptic sites where they were found to influence intrasynaptic NMDA receptor subunit expression. In samples of Kv4.2 knockout mice, the frequency of NR1-positive synapses containing the NR2B subunit was significantly increased. This indicates a strong, yet indirect effect of Kv4.2 on the synaptic content of NMDA receptor subtypes, and a likely role in synaptic plasticity at ITC neurons.
authors.affiliation: Department of Pharmacology, Innsbruck Medical University, Peter-Mayr Strasse 1a, 6020 Innsbruck, Austria. walter.kaufmann@i-med.ac.at
authors.forename: Walter A
authors.initials: WA
authors.lastname: Kaufmann
authors.forename: Ko
authors.initials: K
authors.lastname: Matsui
authors.forename: Andreas
authors.initials: A
authors.lastname: Jeromin
authors.forename: Jeanne M
authors.initials: JM
authors.lastname: Nerbonne
authors.forename: Francesco
authors.initials: F
authors.lastname: Ferraguti
mesh_terms: D000679:Amygdala / Q000166:cytology* / Q000378:metabolism; D000818:Animals; D003712:Dendrites / Q000378:metabolism* / Q000648:ultrastructure; D005614:Freeze Fracturing; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D007150:Immunohistochemistry; D007395:Interneurons / Q000378:metabolism* / Q000648:ultrastructure; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016253:Microscopy, Immunoelectron; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D051672:Shal Potassium Channels / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism*
chemical_list: C121001:NR2B NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate; D051672:Shal Potassium Channels