Identification and characterization of a novel, shorter isoform of the small conductance Ca(2+)-activated K(+) channel SK2

Saravana R. K. Murthy, Georgeta Teodorescu, Ingrid M. Nijholt, Amalia Dolga, Stephan Grissmer, Joachim Spiess, Thomas Blank*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

18 Citations (Scopus)

Abstract

Throughout the CNS, small conductance Ca(2+)-activated potassium (SK) channels modulate firing frequency and neuronal excitability. We have identified a novel, shorter isoform of standard SK2 (SK2-std) in mouse brain which we named SK2-sh. SK2-sh is alternatively spliced at exon 3 and therefore lacks 140 amino acids, which include transmembrane domains S3, S4 and S5, compared with SK2-std. Western blot analysis of mouse hippocampal tissue revealed a 47 kDa protein product as predicted for SK2-sh along with a 64 kDa band representing the standard SK2 isoform. Electrophysiological recordings from transiently expressed SK2-sh revealed no functional channel activity or interaction with SK2-std. With the help of real-time PCR, we found significantly higher expression levels of SK2-sh mRNA in cortical tissue from AD cases when compared with age-matched controls. A similar increase in SK2-sh expression was induced in cortical neurons from mice by cytokine exposure. Substantial clinical evidence suggests that excess cytokines are centrally involved in the pathogenesis of Alzheimer's disease. Thus, SK2-sh as a downstream target of cytokines, provide a promising target for additional investigation regarding potential therapeutic intervention.

Original languageEnglish
Pages (from-to)2312-2321
Number of pages10
JournalJournal of Neurochemistry
Volume106
Issue number6
DOIs
Publication statusPublished - Sep-2008

Keywords

  • Alzheimer's disease
  • cortical neurons
  • small conductance calcium-activated potassium channel
  • splice variant
  • whole-cell recordings
  • NECROSIS-FACTOR-ALPHA
  • ACTIVATED POTASSIUM CHANNELS
  • ALZHEIMERS-DISEASE
  • GLUTAMATE RELEASE
  • APOLIPOPROTEIN-D
  • MOUSE-BRAIN
  • KAPPA-B
  • EXPRESSION
  • NEURONS
  • SUBUNITS

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