title: Novel wasp toxin discriminates between neuronal and cardiac sodium channels.
abstract: Pompilidotoxins (PMTXs), derived from the venom of solitary wasp has been known to facilitate synaptic transmission in the lobster neuromuscular junction, and a recent further study from rat trigeminal neurons revealed that the toxin slows Na+ channel inactivation without modifying activation process. Here we report that beta-PMTX modifies rat brain type II Na+ channel alpha-subunit (rBII) expressed in human embryonic kidney cells but fails to act on the rat heart alpha-subunit (rH1) at similar concentrations. We constructed a series of chimeric mutants of rBII and rH1 Na+ channels and compared modification of the steady-state Na+ currents by beta-PMTX. We found that a difference in a single amino acid between Glu-1616 in rBII and Gln-1615 in rH1 at the extracellular loop of D4S3-S4 is crucial for the action of beta-PMTX. PMTXs, which are small peptides with 13 amino acids, would be a potential tool for exploring a new functional moiety of Na+ channels.
authors.affiliation: Department of Physiology, School of Medicine, Hiroshima University, Kasumi 1-2-3, Hiroshima 734-8551, Japan.
authors.forename: E
authors.initials: E
authors.lastname: Kinoshita
authors.forename: H
authors.initials: H
authors.lastname: Maejima
authors.forename: K
authors.initials: K
authors.lastname: Yamaoka
authors.forename: K
authors.initials: K
authors.lastname: Konno
authors.forename: N
authors.initials: N
authors.lastname: Kawai
authors.forename: E
authors.initials: E
authors.lastname: Shimizu
authors.forename: S
authors.initials: S
authors.lastname: Yokote
authors.forename: H
authors.initials: H
authors.lastname: Nakayama
authors.forename: I
authors.initials: I
authors.lastname: Seyama
mesh_terms: D002478:Cells, Cultured; D003064:Cnidarian Venoms / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D018698:Glutamic Acid / Q000378:metabolism; D006321:Heart / Q000187:drug effects / Q000502:physiology; D006801:Humans; D019476:Insect Proteins; D007700:Kinetics; D009206:Myocardium / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D009498:Neurotoxins / Q000494:pharmacology*; D011487:Protein Conformation; D012604:Scorpion Venoms / Q000494:pharmacology; D015222:Sodium Channels / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D013997:Time Factors; D014162:Transfection; D014862:Wasp Venoms / Q000494:pharmacology*
chemical_list: D003064:Cnidarian Venoms; D019476:Insect Proteins; D009498:Neurotoxins; D012604:Scorpion Venoms; D015222:Sodium Channels; D014862:Wasp Venoms; C115329:pompilidotoxin beta; D018698:Glutamic Acid