Received for publication June 21, 2007.
Revised June 21, 2007.
Accepted for publication June 26, 2007.

The MiRP2-Kv3.4 potassium channel: muscling in on Alzheimer's disease (Relates to article by Pannaccione et al., Fast Forward 10 May 2007)

Abstract

In this issue of Molecular Pharmacology (p xxx), Pannacione et al provide evidence of a role for the voltage-gated potassium channel subunit Kv3.4 and its ancillary subunit MiRP2 in A 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 upregulated by A peptide, considered a significant step in the etiology of Alzheimer's disease. The authors conclude that MiRP2 and Kv3.4 are upregulated by A peptide in an NFB-dependent fashion at the transcriptional level, and the sea anemone toxin BDS-I is shown to protect against A 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.

Key words: Ion channel regulation, NFkappaB