The MiRP2-Kv3.4 potassium channel: muscling in on Alzheimer's disease

Mol Pharmacol. 2007 Sep;72(3):499-501. doi: 10.1124/mol.107.039206. Epub 2007 Jun 26.

Abstract

In this issue of Molecular Pharmacology (p. 665), Pannacione et al. provide evidence of a role for the voltage-gated potassium channel alpha subunit Kv3.4 and its ancillary subunit MiRP2 in beta-amyloid (Abeta) peptide-mediated neuronal death. The MiRP2-Kv3.4 channel complex-previously found to be important in skeletal myocyte physiology-is now argued to be a molecular correlate of the transient outward potassium current up-regulated by Abeta peptide, considered a significant step in the etiology of Alzheimer's disease. The authors conclude that MiRP2 and Kv3.4 are up-regulated by Abeta peptide in a nuclear factor kappaB-dependent fashion at the transcriptional level, and the sea anemone toxin BDS-I is shown to protect against Abeta peptide-mediated cell death by specific blockade of Kv3.4-generated current. The findings lend weight to the premise that specific channels, such as MiRP2-Kv3.4, could hold promise as future therapeutic targets in Alzheimer's disease and potentially other neurodegenerative disorders.

Publication types

  • Comment
  • Research Support, N.I.H., Extramural

MeSH terms

  • Alzheimer Disease / etiology
  • Alzheimer Disease / genetics*
  • Alzheimer Disease / metabolism*
  • Alzheimer Disease / pathology
  • Amyloid beta-Peptides / chemistry
  • Amyloid beta-Peptides / toxicity
  • Animals
  • Apoptosis / drug effects
  • Cell Death / drug effects
  • Cnidarian Venoms / pharmacology
  • Humans
  • Models, Biological
  • Muscle, Skeletal / chemistry
  • Muscle, Skeletal / cytology
  • Muscle, Skeletal / metabolism*
  • NF-kappa B / antagonists & inhibitors
  • Peptide Fragments / chemistry
  • Peptide Fragments / toxicity
  • Potassium Channel Blockers / pharmacology
  • Potassium Channels, Voltage-Gated / antagonists & inhibitors
  • Potassium Channels, Voltage-Gated / physiology*
  • Sea Anemones / chemistry
  • Shaw Potassium Channels / antagonists & inhibitors
  • Shaw Potassium Channels / physiology*

Substances

  • Amyloid beta-Peptides
  • BDS-I antiviral protein, Anemonia sulcata
  • Cnidarian Venoms
  • KCNE3 protein, human
  • NF-kappa B
  • Peptide Fragments
  • Potassium Channel Blockers
  • Potassium Channels, Voltage-Gated
  • Shaw Potassium Channels
  • amyloid beta-protein (1-42)