title: Tetrodotoxin reverses brevetoxin allosteric inhibition of scorpion alpha-toxin binding on rat brain sodium channels.
abstract: Voltage-sensitive sodium channels are responsible for the initiation of action potentials in many excitable cells. Several neurotoxins bind to distinct receptor sites on sodium channels and reveal strong allosteric interactions among them. Scorpion alpha toxins, which inhibit sodium channel inactivation by binding to receptor site 3, have been very important tools to study sodium channel structure and function. Recently, we have shown that brevetoxin induce a strong negative allosteric modulation on scorpion alpha-toxin binding on rat brain sodium channels, in contrast to previously published studies. In this report we have examined the reasons for this discrepancy and found new, unexpected allosteric interactions between the tetrodotoxin and brevetoxin receptor sites, using scorpion alpha-toxin as sensitive probe for subtle conformational changes on sodium channels. Tetrodotoxin reverses the negative modulation induced by brevetoxin on scorpion alpha-toxin binding, revealing new dynamic interactions in sodium channel structure.
authors.affiliation: Laboratory of Biochemistry, CNRS URA 1455, Faculty of Medicine Nord, Jean Roche Institute, Boulevard Pierre Dramard, 13916 Marseille Cedex 20, France.
authors.forename: S
authors.initials: S
authors.lastname: Cestèle
authors.forename: F
authors.initials: F
authors.lastname: Sampieri
authors.forename: H
authors.initials: H
authors.lastname: Rochat
authors.forename: D
authors.initials: D
authors.lastname: Gordon
mesh_terms: D000495:Allosteric Site; D000818:Animals; D001921:Brain / Q000378:metabolism; D004347:Drug Interactions; D066298:In Vitro Techniques; D008387:Marine Toxins / Q000494:pharmacology*; D015394:Molecular Structure; D009498:Neurotoxins / Q000378:metabolism / Q000494:pharmacology*; D035964:Oxocins; D051381:Rats; D017208:Rats, Wistar; D030162:Reptilian Proteins; D012604:Scorpion Venoms / Q000378:metabolism*; D015222:Sodium Channels / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism*; D013779:Tetrodotoxin / Q000494:pharmacology*; D000095702:Polyether Toxins
chemical_list: D008387:Marine Toxins; D009498:Neurotoxins; D035964:Oxocins; D030162:Reptilian Proteins; D012604:Scorpion Venoms; D015222:Sodium Channels; D013779:Tetrodotoxin; C053969:scorpion toxin II, Androctonus; C053342:brevetoxin; D000095702:Polyether Toxins