Unanticipated region- and cell-specific downregulation of individual KChIP auxiliary subunit isotypes in Kv4.2 knock-out mouse brain

Milena Menegola, James Trimmer

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

Kv4 family voltage-gated potassium channel α subunits and Kv channel-interacting protein (KChIP) and dipeptidyl aminopeptidase-like protein subunits comprise somatodendritic A-type channels in mammalian neurons. Recently, a mouse was generated with a targeted deletion of Kv4.2, a Kv4 α subunit expressed in many but not all mammalian brain neurons. Kv4.2 -/- mice are grossly indistinguishable from wild-type (WT) littermates. Here we used immunohistochemistry to analyze expression of component Kv4 and KChIP subunits of A-type channels in WT and Kv4.2 -/- brains. We found that the expression level, and cellular and subcellular distribution of the other prominent brain Kv4 family member Kv4.3, was indistinguishable between WT and Kv4.2-/- samples. However, we found unanticipated regional and cell-specific decreases in expression of KChIPs. The degree of altered expression of individual KChIP isoforms in different regions and neurons precisely follows the level of Kv4.2 normally found at those sites and presumably their extent of association of these KChIPs with Kv4.2. The dramatic effects of Kv4.2 deletion on KChIP expression suggest that, in addition to previously characterized effects of KChIPs on the functional properties, trafficking, and turnover rate of Kv4 channels, Kv4:KChIP association may confer reciprocal Kv4.2-dependent effects on KChIPs. The impact of Kv4.2 deletion on KChIP expression also supports the major role of KChIPs as auxiliary subunits of Kv4 channels.

Original languageEnglish (US)
Pages (from-to)12137-12142
Number of pages6
JournalJournal of Neuroscience
Volume26
Issue number47
DOIs
StatePublished - Nov 22 2006

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Kv Channel-Interacting Proteins
Protein Subunits
Knockout Mice
Down-Regulation
Brain
Neurons
Voltage-Gated Potassium Channels
Aminopeptidases
Protein Isoforms
Immunohistochemistry

Keywords

  • Cerebellum
  • Dendrite
  • Excitability
  • Hippocampus
  • Immunohistochemistry
  • Ion channel

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Unanticipated region- and cell-specific downregulation of individual KChIP auxiliary subunit isotypes in Kv4.2 knock-out mouse brain. / Menegola, Milena; Trimmer, James.

In: Journal of Neuroscience, Vol. 26, No. 47, 22.11.2006, p. 12137-12142.

Research output: Contribution to journalArticle

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