title: Inhibition of Sodium Ion Channel Function with Truncated Forms of Batrachotoxin.
abstract: A novel family of small molecule inhibitors of voltage-gated sodium channels (NaVs) based on the structure of batrachotoxin (BTX), a well-known channel agonist, is described. Protein mutagenesis and electrophysiology experiments reveal the binding site as the inner pore region of the channel, analogous to BTX, alkaloid toxins, and local anesthetics. Homology modeling of the eukaryotic channel based on recent crystallographic analyses of bacterial NaVs suggests a mechanism of action for ion conduction block.
authors: Department of Chemistry, Stanford University , Stanford, California 94305-5080, United States.
authors: Tatsuya
authors: T
authors: Toma
authors: Department of Chemistry, Stanford University , Stanford, California 94305-5080, United States.
authors: Matthew M
authors: MM
authors: Logan
authors: Department of Chemistry, Stanford University , Stanford, California 94305-5080, United States.
authors: Frederic
authors: F
authors: Menard
authors: Department of Chemistry, Stanford University , Stanford, California 94305-5080, United States.
authors: A Sloan
authors: AS
authors: Devlin
authors: Department of Chemistry, Stanford University , Stanford, California 94305-5080, United States.
authors: J
authors: J
authors: Du Bois
mesh_terms: D000818:Animals; D001496:Batrachotoxins / Q000032:analysis* / Q000138:chemical synthesis / Q000494:pharmacology*; D016466:CHO Cells; D003412:Cricetulus; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D008958:Models, Molecular; D015394:Molecular Structure; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D018408:Patch-Clamp Techniques; D051381:Rats; D026941:Sodium Channel Blockers / Q000138:chemical synthesis / Q000494:pharmacology*; D015222:Sodium Channels / Q000235:genetics / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D001496:Batrachotoxins; D009124:Muscle Proteins; C466180:Scn4a protein, rat; D026941:Sodium Channel Blockers; D015222:Sodium Channels
keywords: SAR; Site II; batrachotoxin; electrophysiology; protein mutagenesis; sodium channel