Charybdotoxin (CTX) is a 37 amino acid neurotoxin from the venom of the scorpion Leiurus quinquestriatus hebraeus (Deathstalker) that blocks calcium-activated potassium channels. This blockade causes hyperexcitability of the nervous system. It is a close homologue of agitoxin and both toxins come from Leiurus quinquestriatus hebraeus. Charybdotoxin occludes the pore of calcium-activated voltage-gated Shaker K+ channels by binding to one of four independent, overlapping binding sites. It binds both to the open and the closed states. In addition, the block is enhanced as the ionic strength is lowered. This block occurs as the Asn 30 on the CTX interacts with the Asp 381 on the K+ channel. The blockade of K+ channels by the charybdotoxin peptide causes neuronal hyperexcitability. Mutations of the Lys31Gln and the Asn30Gln had the effect of lessening the CTX block of the pore on the Shaker channel.
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