Abstract

In this issue of Molecular Pharmacology (p. 665), Pannacione et al. provide evidence of a role for the voltage-gated potassium channel α subunit Kv3.4 and its ancillary subunit MiRP2 in β-amyloid (Aβ) 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 Aβ peptide, considered a significant step in the etiology of Alzheimer's disease. The authors conclude that MiRP2 and Kv3.4 are up-regulated by Aβ peptide in a nuclear factor κB-dependent fashion at the transcriptional level, and the sea anemone toxin BDS-I is shown to protect against Aβ 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.