title: KChIPs and Kv4 alpha subunits as integral components of A-type potassium channels in mammalian brain.
abstract: Voltage-gated potassium (Kv) channels from the Kv4, or Shal-related, gene family underlie a major component of the A-type potassium current in mammalian central neurons. We recently identified a family of calcium-binding proteins, termed KChIPs (Kv channel interacting proteins), that bind to the cytoplasmic N termini of Kv4 family alpha subunits and modulate their surface density, inactivation kinetics, and rate of recovery from inactivation (An et al., 2000). Here, we used single and double-label immunohistochemistry, together with circumscribed lesions and coimmunoprecipitation analyses, to examine the regional and subcellular distribution of KChIPs1-4 and Kv4 family alpha subunits in adult rat brain. Immunohistochemical staining using KChIP-specific monoclonal antibodies revealed that the KChIP polypeptides are concentrated in neuronal somata and dendrites where their cellular and subcellular distribution overlaps, in an isoform-specific manner, with that of Kv4.2 and Kv4.3. For example, immunoreactivity for KChIP1 and Kv4.3 is concentrated in the somata and dendrites of hippocampal, striatal, and neocortical interneurons. Immunoreactivity for KChIP2, KChIP4, and Kv4.2 is concentrated in the apical and basal dendrites of hippocampal and neocortical pyramidal cells. Double-label immunofluorescence labeling revealed that throughout the forebrain, KChIP2 and KChIP4 are frequently colocalized with Kv4.2, whereas in cortical, hippocampal, and striatal interneurons, KChIP1 is frequently colocalized with Kv4.3. Coimmunoprecipitation analyses confirmed that all KChIPs coassociate with Kv4 alpha subunits in brain membranes, indicating that KChIPs 1-4 are integral components of native A-type Kv channel complexes and are likely to play a major role as modulators of somatodendritic excitability.
authors.affiliation: Neuroscience, Wyeth Discovery Research, Princeton, New Jersey 08543, USA.
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Rhodes
authors.forename: Karen I
authors.initials: KI
authors.lastname: Carroll
authors.forename: M Amy
authors.initials: MA
authors.lastname: Sung
authors.forename: Lisa C
authors.initials: LC
authors.lastname: Doliveira
authors.forename: Michael M
authors.initials: MM
authors.lastname: Monaghan
authors.forename: Sharon L
authors.initials: SL
authors.lastname: Burke
authors.forename: Brian W
authors.initials: BW
authors.lastname: Strassle
authors.forename: Lynn
authors.initials: L
authors.lastname: Buchwalder
authors.forename: Milena
authors.initials: M
authors.lastname: Menegola
authors.forename: Jie
authors.initials: J
authors.lastname: Cao
authors.forename: W Frank
authors.initials: WF
authors.lastname: An
authors.forename: James S
authors.initials: JS
authors.lastname: Trimmer
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000918:Antibody Specificity; D001923:Brain Chemistry; D019556:COS Cells; D002135:Calcium-Binding Proteins / Q000502:physiology*; D002522:Chlorocebus aethiops; D003342:Corpus Striatum / Q000166:cytology / Q000378:metabolism; D003712:Dendrites / Q000737:chemistry / Q000648:ultrastructure; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D007051:Ibotenic Acid / Q000633:toxicity; D047468:Immunoprecipitation; D007395:Interneurons / Q000737:chemistry / Q000502:physiology; D051605:Kv Channel-Interacting Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D008856:Microscopy, Fluorescence; D019579:Neocortex / Q000166:cytology / Q000378:metabolism; D009473:Neuronal Plasticity; D009474:Neurons / Q000737:chemistry / Q000187:drug effects / Q000502:physiology; D015221:Potassium Channels / Q000502:physiology*; D024642:Potassium Channels, Voltage-Gated / Q000502:physiology*; D025941:Protein Interaction Mapping; D021122:Protein Subunits; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000502:physiology; D012097:Repressor Proteins / Q000502:physiology*; D051672:Shal Potassium Channels; D009435:Synaptic Transmission / Q000502:physiology; D014162:Transfection
chemical_list: D000911:Antibodies, Monoclonal; D002135:Calcium-Binding Proteins; C496756:Csen protein, mouse; C497020:Kcnd2 protein, rat; C497022:Kcnd3 protein, mouse; C497023:Kcnd3 protein, rat; C496754:Kcnip1 protein, mouse; C496757:Kcnip1 protein, rat; C496755:Kcnip2 protein, mouse; C496758:Kcnip2 protein, rat; C496760:Kcnip3 protein, rat; C452817:Kcnip4 protein, rat; D051605:Kv Channel-Interacting Proteins; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D021122:Protein Subunits; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D051672:Shal Potassium Channels; D007051:Ibotenic Acid