title: Point-mutations related to the loss of batrachotoxin binding abolish the grayanotoxin effect in Na(+) channel isoforms.
abstract: The effect of grayanotoxin (GTX) on site-specific mutants of the alpha-subunit of rat skeletal muscle Na(+) channels (micro1) (micro1-I433K, micro1-N434K and micro1-L437K), which are resistant to batrachotoxin (BTX) (Wang and Wang (1998) Proc Natl Acad Sci USA, 95, 2653-2658) was studied using a whole-cell patch-clamp method. The GTX modification of the Na(+) channels was detected as a characteristic-sustained Na(+) current flow with repetitive pulses. We also studied the GTX action on mutants of the alpha-subunit of rat heart Na(+) channels (RH1) (RH1-V406K and RH1-L410K) which match with micro1-I433 and micro1-L437. All the mutants lost their sensitivity to GTX. This finding indicates that GTX may share a binding site with BTX in transmembrane segment I-S6 of two different Na(+) channel isoforms, micro1 and RH1.
authors.affiliation: Department of Physiology, School of Medicine, Hiroshima University, Hiroshima, 734-8551, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Ishii
authors.forename: E
authors.initials: E
authors.lastname: Kinoshita
authors.forename: T
authors.initials: T
authors.lastname: Kimura
authors.forename: M
authors.initials: M
authors.lastname: Yakehiro
authors.forename: K
authors.initials: K
authors.lastname: Yamaoka
authors.forename: K
authors.initials: K
authors.lastname: Imoto
authors.forename: Y
authors.initials: Y
authors.lastname: Mori
authors.forename: I
authors.initials: I
authors.lastname: Seyama
mesh_terms: D000818:Animals; D001496:Batrachotoxins / Q000378:metabolism / Q000494:pharmacology*; D017931:DNA Primers; D004224:Diterpenes / Q000378:metabolism / Q000494:pharmacology*; D015640:Ion Channel Gating / Q000187:drug effects / Q000235:genetics; D007536:Isomerism; D018482:Muscle, Skeletal / Q000737:chemistry; D016297:Mutagenesis, Site-Directed / Q000502:physiology; D018408:Patch-Clamp Techniques; D017354:Point Mutation; D051381:Rats; D015222:Sodium Channels / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*
chemical_list: D001496:Batrachotoxins; D017931:DNA Primers; D004224:Diterpenes; D015222:Sodium Channels; C020750:grayanotoxin II