The MiRP2-kv3.4 potassium channel: muscling in on Alzheimer's disease

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 ( A beta) peptide- mediated neuronal death. The MiRP2Kv3.4 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 A beta peptide, considered a significant step in the etiology of Alzheimer's disease. The authors conclude that MiRP2 and Kv3.4 are up- regulated by A beta peptide in a nuclear factor kappa B- dependent fashion at the transcriptional level, and the sea anemone toxin BDS- I is shown to protect against A beta peptidemediated 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.