KChIPs and Kv4 α subunits as integral components of A-type potassium channels in mammalian brain

Kenneth J. Rhodes, Karen I. Carroll, M. Amy Sung, Lisa C. Doliveira, Michael M. Monaghan, Sharon L. Burke, Brian W. Strassle, Lynn Buchwalder, Milena Menegola, Jie Cao, W. Frank An, James Trimmer

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195 Scopus citations

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 α 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 KChIPs 1-4 and Kv4 family a 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 KChIP1, 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 α 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.

Original languageEnglish (US)
Pages (from-to)7903-7915
Number of pages13
JournalJournal of Neuroscience
Volume24
Issue number36
DOIs
StatePublished - Sep 8 2004

Keywords

  • A current
  • Alzheimer's disease
  • Hippocampus
  • Long-term potentiation
  • Shal
  • Synaptic plasticity

ASJC Scopus subject areas

  • Neuroscience(all)

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  • Cite this

    Rhodes, K. J., Carroll, K. I., Sung, M. A., Doliveira, L. C., Monaghan, M. M., Burke, S. L., Strassle, B. W., Buchwalder, L., Menegola, M., Cao, J., An, W. F., & Trimmer, J. (2004). KChIPs and Kv4 α subunits as integral components of A-type potassium channels in mammalian brain. Journal of Neuroscience, 24(36), 7903-7915. https://doi.org/10.1523/JNEUROSCI.0776-04.2004