Mechanism of charybdotoxin block of a voltage-gated K+ channel.
Charybdotoxin block of a Shaker K+ channel was studied in Xenopus oocyte macropatches. Toxin on rate increases linearly with toxin concentration in an ionic strength-dependent fashion and is competitively diminished by tetraethylammonium. On rate is insensitive to transmembrane voltage and to K+ on the opposite side of the membrane. Conversely, toxin off rate is insensitive to toxin concentration, ionic strength, and added tetraethylammonium but is enhanced by membrane depolarization or K+ (or Na+) in the trans solution. Charge neutralization of charybdotoxin Lys27, however, renders off rate voltage insensitive. Our results argue that block of voltage-gated K+ channels results from the binding of one toxin molecule, so that Lys27 enters the pore and interacts with K+ (or Na+) in the ion conduction pathway.
Goldstein
S A
SA
Howard Hughes Medical Institute, Graduate Department of Biochemistry, Brandeis University, Waltham, MA 02254-9110.
Miller
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C
D000818:Animals; D001667:Binding, Competitive; D055592:Biophysical Phenomena; D001703:Biophysics; D018999:Charybdotoxin; D004330:Drosophila; D005260:Female; D015640:Ion Channel Gating; D007700:Kinetics; D008564:Membrane Potentials; D009154:Mutation; D009865:Oocytes / Q000187:drug effects / Q000378:metabolism; D010455:Peptides / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000494:pharmacology; D012604:Scorpion Venoms / Q000235:genetics / Q000494:pharmacology*; D051637:Shaker Superfamily of Potassium Channels; D014981:Xenopus
D010455:Peptides; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D011994:Recombinant Proteins; D012604:Scorpion Venoms; C076413:Shaker B potassium channel polypeptide; D051637:Shaker Superfamily of Potassium Channels; D018999:Charybdotoxin