title: A toxin to nervous, cardiac, and endocrine ERG K+ channels isolated from Centruroides noxius scorpion venom.
abstract: Toxins isolated from a variety of venoms are tools for probing the physiological function and structure of ion channels. The ether-a-go-go-related genes (erg) codify for the K+ channels (ERG), which are crucial in neurons and are impaired in human long-QT syndrome and Drosophila 'seizure' mutants. We have isolated a peptide from the scorpion Centruroides noxius Hoffmann that has no sequence homologies with other toxins, and demonstrate that it specifically inhibits (IC50=16+/-1 nM) only ERG channels of different species and distinct histogenesis. These results open up the possibility of investigating ERG channel structure-function relationships and novel pharmacological tools with potential therapeutic efficacy.
authors.affiliation: Department of Biotechnology and Biosciences, University of Milano-Bicocca, 20126 Milano, Italy.
authors.forename: G B
authors.initials: GB
authors.lastname: Gurrola
authors.forename: B
authors.initials: B
authors.lastname: Rosati
authors.forename: M
authors.initials: M
authors.lastname: Rocchetti
authors.forename: G
authors.initials: G
authors.lastname: Pimienta
authors.forename: A
authors.initials: A
authors.lastname: Zaza
authors.forename: A
authors.initials: A
authors.lastname: Arcangeli
authors.forename: M
authors.initials: M
authors.lastname: Olivotto
authors.forename: L D
authors.initials: LD
authors.lastname: Possani
authors.forename: E
authors.initials: E
authors.lastname: Wanke
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000595:Amino Acid Sequence; D000818:Animals; D027682:Cation Transport Proteins; D002460:Cell Line; D004268:DNA-Binding Proteins; D004305:Dose-Response Relationship, Drug; D000072237:ERG1 Potassium Channel; D004702:Endocrine Glands / Q000187:drug effects / Q000378:metabolism; D051638:Ether-A-Go-Go Potassium Channels; D006168:Guinea Pigs; D006801:Humans; D007700:Kinetics; D051379:Mice; D008969:Molecular Sequence Data; D009206:Myocardium / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000235:genetics; D024642:Potassium Channels, Voltage-Gated; D051381:Rats; D012604:Scorpion Venoms / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification* / Q000633:toxicity*; D012605:Scorpions; D017386:Sequence Homology, Amino Acid; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG
chemical_list: D027682:Cation Transport Proteins; D004268:DNA-Binding Proteins; C072312:ERG protein, human; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; C000606913:KCNH2 protein, human; C092509:KCNH6 protein, human; C000606915:Kcnh2 protein, mouse; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D012604:Scorpion Venoms; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG; C118951:ergotoxin, Centruroides noxius