title: Subtype specificity interaction of bactridines with mammalian, insect and bacterial sodium channels under voltage clamp conditions.
abstract: The present work demonstrates that bactridines (Bacts) possess different selectivities for neuronal and muscular voltage-dependent sodium (Na(V) ) channels, with subtle differences on channel isoforms. Bacts 2, 3, 4, 5 and 6 (100 nm) reduced the peak current of several skeletal and neuronal channel isoforms selectively. Bacts 2 and 3 were more potent on Na(V) 1.4, Bacts 4 and 6 on Na(V) 1.3 and Bact 5 on Na(V) 1.7. Bactridines (except Bacts 1 and 5) caused a hyperpolarizing shift in the V(1/2)  of activation and inactivation of Na(V) 1.3, Na(V) 1.4 and Na(V) 1.6. Voltage shifts of Boltzmann curves fitted to activation and inactivation occurred with a decrease in κ. Since the slope is proportional to κ = RT/zF, changes in κ probably express changes in z, the valence, in a voltage-dependent manner. Changes in z may express toxin-induced changes in the channel ionic environment, perhaps due to surface charges of the molecules. Bact 2 induced a Na(V) 1.2 voltage shift of the activation curves but no shift of the mutant Na(V) 1.2 IFM/QQQ; peak I(N)             (a)  was reduced in both channel forms, suggesting that channel blockage resulted from toxin binding to a site partially distinct from the α subunit binding site 4. Bactridines emerge as potential research tools to understand sodium channel isoform structure-function relationships and also as pharmacologically interesting peptides.
authors.affiliation: Laboratory of Toxicology, University of Leuven (K.U. Leuven), Belgium.
authors.forename: Steve
authors.initials: S
authors.lastname: Peigneur
authors.forename: Carlos
authors.initials: C
authors.lastname: Sevcik
authors.forename: Jan
authors.initials: J
authors.lastname: Tytgat
authors.forename: Cecilia
authors.initials: C
authors.lastname: Castillo
authors.forename: Gina
authors.initials: G
authors.lastname: D'Suze
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001419:Bacteria; D002478:Cells, Cultured; D005260:Female; D007313:Insecta; D015640:Ion Channel Gating / Q000187:drug effects*; D008322:Mammals; D008564:Membrane Potentials / Q000187:drug effects; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D020033:Protein Isoforms; D017386:Sequence Homology, Amino Acid; D013329:Structure-Activity Relationship; D014118:Toxins, Biological / Q000494:pharmacology*; D061566:Voltage-Gated Sodium Channels / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D014982:Xenopus laevis
chemical_list: D020033:Protein Isoforms; D014118:Toxins, Biological; D061566:Voltage-Gated Sodium Channels