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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Action Potentials / drug effects
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Amino Acid Sequence
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Animals
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Cation Transport Proteins*
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Cell Line
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DNA-Binding Proteins*
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Dose-Response Relationship, Drug
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ERG1 Potassium Channel
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Endocrine Glands / drug effects
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Endocrine Glands / metabolism
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Ether-A-Go-Go Potassium Channels
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Guinea Pigs
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Humans
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Kinetics
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Mice
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Molecular Sequence Data
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Myocardium / metabolism
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Neurons / drug effects
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Neurons / metabolism
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Potassium Channel Blockers*
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Potassium Channels / genetics
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Potassium Channels, Voltage-Gated*
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Rats
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Scorpion Venoms / chemistry*
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Scorpion Venoms / genetics
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Scorpion Venoms / isolation & purification*
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Scorpion Venoms / toxicity*
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Scorpions
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Sequence Homology, Amino Acid
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Trans-Activators*
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Transcriptional Regulator ERG
Substances
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Cation Transport Proteins
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DNA-Binding Proteins
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ERG protein, human
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ERG1 Potassium Channel
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Ether-A-Go-Go Potassium Channels
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KCNH2 protein, human
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KCNH6 protein, human
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Kcnh2 protein, mouse
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Potassium Channel Blockers
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Potassium Channels
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Potassium Channels, Voltage-Gated
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Scorpion Venoms
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Trans-Activators
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Transcriptional Regulator ERG
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ergotoxin, Centruroides noxius