title: Cn11, the first example of a scorpion toxin that is a true blocker of Na(+) currents in crayfish neurons.
abstract: A novel crustacean toxin (Cn11) was isolated and characterized from the venom of the Mexican scorpion Centruroides noxius Hoffmann. It contains 63 amino acid residues and is stabilized by four disulphide bridges. It is lethal to crustaceans (Cambarellus montezumae), less toxic to insects (crickets) and non-toxic to mammals (mice) at the doses assayed. In neurons isolated from the X organ-sinus gland system of the crayfish Procambarus clarkii, it blocks the Na(+) currents with an estimated K(m) of 320 nmol l(-1), without affecting the Ca(2+) and K(+) currents. The voltage-gated tetrodotoxin-sensitive Na(+) current was recorded from X organ neurons in culture 24 h after plating using the whole-cell clamp configuration. The Na(+) current was isolated by blocking Ca(2+) currents with Cd(2+) and Cs(+) and K(+) currents with tetraethylammonium and 4-aminopyridine. Under control conditions, the Na(+) currents were activated at -40 mV with a maximum amplitude at 0 mV. In the presence of 1 micromol l(-1) Cn11, the Na(+) current amplitude was reduced by 75 % without apparent modifications to the gating mechanism. These findings suggest that Cn11 selectively blocks a Na(+) channel. It is the first representative of a new group of scorpion toxins specific for this molecular target.
authors.affiliation: Department of Molecular Recognition and Structural Biology, Biotechnology Institute, Universidad Nacional Autónoma de México, Avenida Universidad 2001, Cuernavaca 62210, México.
authors.forename: Martha E
authors.initials: ME
authors.lastname: Ramirez-Dominguez
authors.forename: Timoteo
authors.initials: T
authors.lastname: Olamendi-Portugal
authors.forename: Ubaldo
authors.initials: U
authors.lastname: Garcia
authors.forename: Consuelo
authors.initials: C
authors.lastname: Garcia
authors.forename: Hugo
authors.initials: H
authors.lastname: Arechiga
authors.forename: Lourival D
authors.initials: LD
authors.lastname: Possani
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D003400:Astacoidea; D015220:Calcium Channels / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004553:Electric Conductivity; D015640:Ion Channel Gating / Q000187:drug effects; D007700:Kinetics; D008969:Molecular Sequence Data; D009474:Neurons / Q000737:chemistry* / Q000502:physiology; D015221:Potassium Channels / Q000187:drug effects; D012604:Scorpion Venoms / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D020539:Sequence Analysis, Protein; D026941:Sodium Channel Blockers / Q000494:pharmacology*; D015222:Sodium Channels / Q000502:physiology; D013779:Tetrodotoxin / Q000494:pharmacology
chemical_list: D015220:Calcium Channels; D015221:Potassium Channels; D012604:Scorpion Venoms; D026941:Sodium Channel Blockers; D015222:Sodium Channels; C460224:toxin 11, Centruroides noxius; D013779:Tetrodotoxin