Abstract
We have studied the interaction of CnErg1, a member of the gamma-KTX subfamily of scorpion toxins with the inactivation-deficient S631A hERG channel. In the background of this mutation, we observed a mechanistic switch from turret block, characteristic of the action of gamma-KTXs on Kv11-type channels, to pore plugging, characteristic of alpha-KTX block of Kv1-type channels. We suggest this reflects destabilization of the outer pore (turret region) of hERG allowing access of the toxin molecule to directly plug the conduction pathway.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Substitution
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Animals
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Biophysical Phenomena
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Biophysics
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ERG1 Potassium Channel
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Ether-A-Go-Go Potassium Channels / antagonists & inhibitors*
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Ether-A-Go-Go Potassium Channels / chemistry
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Ether-A-Go-Go Potassium Channels / genetics*
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Ether-A-Go-Go Potassium Channels / metabolism
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Humans
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In Vitro Techniques
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Ion Channel Gating / drug effects
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Membrane Potentials / drug effects
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Mutagenesis, Site-Directed
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Scorpion Venoms / toxicity*
Substances
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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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Scorpion Venoms
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ergotoxin, Centruroides noxius