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 (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.
Choi
Eun
E
Greenberg Division of Cardiology, Department of Medicine, Cornell University, Weill Medical College, New York, NY 10021, USA.
Abbott
Geoffrey W
GW
D000544:Alzheimer Disease / Q000209:etiology / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000633:toxicity; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D003064:Cnidarian Venoms / Q000494:pharmacology; D006801:Humans; D008954:Models, Biological; D018482:Muscle, Skeletal / Q000737:chemistry / Q000166:cytology / Q000378:metabolism*; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D010446:Peptide Fragments / Q000737:chemistry / Q000633:toxicity; D026902:Potassium Channel Blockers / Q000494:pharmacology; D024642:Potassium Channels, Voltage-Gated / Q000037:antagonists & inhibitors / Q000502:physiology*; D012615:Sea Anemones / Q000737:chemistry; D051670:Shaw Potassium Channels / Q000037:antagonists & inhibitors / Q000502:physiology*
D016229:Amyloid beta-Peptides; C059796:BDS-I antiviral protein, Anemonia sulcata; D003064:Cnidarian Venoms; C418492:KCNE3 protein, human; D016328:NF-kappa B; D010446:Peptide Fragments; D026902:Potassium Channel Blockers; D024642:Potassium Channels, Voltage-Gated; D051670:Shaw Potassium Channels; C075222:amyloid beta-protein (1-42)