Charybdotoxin is a new member of the K sup + channel toxin family that includes dendrotoxin I and mast cell degranulating peptide

Journal Article · Tue Dec 12 04:00:00 EST 1989 · Biochemistry; (USA)

DOI:https://doi.org/10.1021/bi00451a025· OSTI ID:7138149

Schweitz, H; Bidard, J N; Lazdunski, M ^[1]; Maes, P ^[2]

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1. Universite de Nice (France)
2. Institut Pasteur de Lille (France)

A polypeptide was identified in the venom of the scorpion Leiurus quinquestriatus hebraeus by its potency to inhibit the high affinity binding of the radiolabeled snake venom toxin dendrotoxin I ({sup 125}I-DTX{sub I}) to its receptor site. It has been purified, and its properties investigated by different techniques were found to be similar to those of MCD and DTX{sub I}, two polypeptide toxins active on a voltage-dependent K{sup +} channel. However, its amino acid sequence was determined, and it was shown that this toxin is in fact charybdotoxin (ChTX), a toxin classically used as a specific tool to block one class of Ca{sup 2+}-activated K{sup +} channels. ChTX, DTX{sub I}, and MCD are potent convulsants and are highly toxic when injected intracerebroventricularly in mice. Their toxicities correlate well with their affinities for their receptors in rat brain. These three structurally different toxins release ({sup 3}H)GABA from preloaded synaptosomes, the efficiency order being DTX{sub I} > ChTX > MCD. Both binding and cross-linking experiments of ChTX to rat brain membranes and to the purified MCD/DTX{sub I} binding protein have shown that the {alpha}-subunit of the MCD/DTX{sub I}-sensitive K{sup +} channel protein also contains the ChTX binding sites. Binding sites for DTX{sub I}, MCD, and ChTX are in negative allosteric interaction. The results show that charybdotoxin belongs to the family of toxins which already includes the dendrotoxins and MCD, which are blockers of voltage-sensitive K{sup +} channels. ChTX is clearly not selective for Ca{sup 2+}-activated K{sup +} channel.

• OSTI ID: 7138149
• Journal Information: Biochemistry; (USA), Journal Name: Biochemistry; (USA) Vol. 28:25; ISSN 0006-2960; ISSN BICHA
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ALKALI METAL COMPOUNDS
AMINO ACID SEQUENCE
ANIMAL CELLS
ANIMALS
ANTIGENS
ARACHNIDS
ARTHROPODS
AUTONOMIC NERVOUS SYSTEM AGENTS
BETA DECAY RADIOISOTOPES
CHEMICAL REACTIONS
CONNECTIVE TISSUE CELLS
CROSS-LINKING
DAYS LIVING RADIOISOTOPES
DRUGS
ELECTRON CAPTURE RADIOISOTOPES
HYDROGEN COMPOUNDS
INTERMEDIATE MASS NUCLEI
INVERTEBRATES
IODINE 125
IODINE ISOTOPES
ISOTOPES
MAST CELLS
MATERIALS
MEMBRANE PROTEINS
MOLECULAR STRUCTURE
NEUROREGULATORS
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
PEPTIDES
PHYSIOLOGY
POLYMERIZATION
POLYPEPTIDES
POTASSIUM COMPOUNDS
PROTEINS
PURIFICATION
RADIOISOTOPES
RECEPTORS
SCORPIONS
SOMATIC CELLS
TOXIC MATERIALS
TOXINS
TRITIUM COMPOUNDS