The Janus-faced atracotoxins are specific blockers of invertebrate K Ca channels

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dc.contributor.author Gunning, SJ
dc.contributor.author Maggio, F
dc.contributor.author Windley, MJ
dc.contributor.author Valenzuela, SM
dc.contributor.author King, GF
dc.contributor.author Nicholson, GM
dc.date.accessioned 2010-05-28T09:45:48Z
dc.date.issued 2008-08
dc.identifier.citation FEBS Journal, 2008, 275 (16), pp. 4045 - 4059
dc.identifier.issn 1742-464X
dc.identifier.other C1 en_US
dc.identifier.uri http://hdl.handle.net/10453/8847
dc.description.abstract The Janus-faced atracotoxins are a unique family of excitatory peptide toxins that contain a rare vicinal disulfide bridge. Although lethal to a wide range of invertebrates, their molecular target has remained enigmatic for almost a decade. We demonstrate here that these toxins are selective, high-affinity blockers of invertebrate Ca2+-activated K+ (K Ca) channels. Janus-faced atracotoxin (J-ACTX)-Hv1c, the prototypic member of this toxin family, selectively blocked KCa channels in cockroach unpaired dorsal median neurons with an IC50 of 2 nm, but it did not significantly affect a wide range of other voltage-activated K +, Ca2+ or Na+ channel subtypes. J-ACTX-Hv1c blocked heterologously expressed cockroach large-conductance Ca 2+-activated K+ (pSlo) channels without a significant shift in the voltage dependence of activation. However, the block was voltage-dependent, indicating that the toxin probably acts as a pore blocker rather than a gating modifier. The molecular basis of the insect selectivity of J-ACTX-Hv1c was established by its failure to significantly inhibit mouse mSlo currents (IC50 ∼ 10 μm) and its lack of activity on rat dorsal root ganglion neuron KCa channel currents. This study establishes the Janus-faced atracotoxins as valuable tools for the study of invertebrate KCa channels and suggests that KCa channels might be potential insecticide targets. © 2008 The Authors.
dc.language eng
dc.relation.isbasedon 10.1111/j.1742-4658.2008.06545.x
dc.subject Alaine-scan mutants, Bioinsecticide, BKCa channel, Cockroach neurons, Kappa-atracotoxin, alaine-scan mutants, bioinsecticide, BK(Ca) channel, cockroach neurons, kappa-atracotoxin, Animals, Humans, Mice, Rats, Neurons, Periplaneta, Cell Line, Potassium Channels, Calcium-Activated, Potassium Channels, Voltage-Gated, Insecticides, Patch-Clamp Techniques, Sequence Homology, Amino Acid, Amino Acid Sequence, Molecular Sequence Data, Models, Molecular, Electric Conductivity, Potassium Channel Blockers, Spider Venoms, Amino Acid Sequence, Animals, Cell Line, Electric Conductivity, Humans, Insecticides, Mice, Models, Molecular, Molecular Sequence Data, Neurons, Patch-Clamp Techniques, Periplaneta, Potassium Channel Blockers, Potassium Channels, Calcium-Activated, Potassium Channels, Voltage-Gated, Rats, Sequence Homology, Amino Acid, Spider Venoms, alaine-scan mutants, bioinsecticide, BKCa channel, cockroach neurons, kappaatracotoxin, Biochemistry & Molecular Biology
dc.subject Alaine-scan mutants; Bioinsecticide; BKCa channel; Cockroach neurons; Kappa-atracotoxin; alaine-scan mutants; bioinsecticide; BK(Ca) channel; cockroach neurons; kappa-atracotoxin; Animals; Humans; Mice; Rats; Neurons; Periplaneta; Cell Line; Potassium Channels, Calcium-Activated; Potassium Channels, Voltage-Gated; Insecticides; Patch-Clamp Techniques; Sequence Homology, Amino Acid; Amino Acid Sequence; Molecular Sequence Data; Models, Molecular; Electric Conductivity; Potassium Channel Blockers; Spider Venoms; Amino Acid Sequence; Animals; Cell Line; Electric Conductivity; Humans; Insecticides; Mice; Models, Molecular; Molecular Sequence Data; Neurons; Patch-Clamp Techniques; Periplaneta; Potassium Channel Blockers; Potassium Channels, Calcium-Activated; Potassium Channels, Voltage-Gated; Rats; Sequence Homology, Amino Acid; Spider Venoms; alaine-scan mutants; bioinsecticide; BKCa channel; cockroach neurons; kappaatracotoxin; Biochemistry & Molecular Biology
dc.title The Janus-faced atracotoxins are specific blockers of invertebrate K Ca channels
dc.type Journal Article
dc.description.version Published
dc.description.version Published
dc.description.version Published
dc.parent FEBS Journal
dc.journal.volume 16
dc.journal.volume 275
dc.journal.number 16 en_US
dc.publocation Commerce Place, 350 Main Street, Malden, MA02148, USA en_US
dc.identifier.startpage 4045 en_US
dc.identifier.endpage 4059 en_US
dc.cauo.name SCI.Medical and Molecular Biosciences en_US
dc.conference Verified OK en_US
dc.for 1101 Medical Biochemistry and Metabolomics
dc.personcode 014211 en_US
dc.personcode 0000032956 en_US
dc.personcode 10044028 en_US
dc.personcode 010690 en_US
dc.personcode 0000043010 en_US
dc.personcode 870145 en_US
dc.percentage 100 en_US
dc.classification.name Medical Biochemistry and Metabolomics en_US
dc.classification.type FOR-08 en_US
dc.edition en_US
dc.custom en_US
dc.date.activity en_US
dc.location.activity ISI:000257988000008 en_US
dc.description.keywords alaine-scan mutants; bioinsecticide; BKCa channel; cockroach neurons; kappaatracotoxin en_US
dc.description.keywords alaine-scan mutants
dc.description.keywords bioinsecticide
dc.description.keywords BK(Ca) channel
dc.description.keywords cockroach neurons
dc.description.keywords kappa-atracotoxin
dc.description.keywords alaine-scan mutants
dc.description.keywords bioinsecticide
dc.description.keywords BK(Ca) channel
dc.description.keywords cockroach neurons
dc.description.keywords kappa-atracotoxin
dc.description.keywords alaine-scan mutants
dc.description.keywords bioinsecticide
dc.description.keywords BK(Ca) channel
dc.description.keywords cockroach neurons
dc.description.keywords kappa-atracotoxin
dc.description.keywords Alaine-scan mutants
dc.description.keywords Bioinsecticide
dc.description.keywords BKCa channel
dc.description.keywords Cockroach neurons
dc.description.keywords Kappa-atracotoxin
dc.description.keywords Alaine-scan mutants
dc.description.keywords Bioinsecticide
dc.description.keywords BKCa channel
dc.description.keywords Cockroach neurons
dc.description.keywords Kappa-atracotoxin
dc.description.keywords Alaine-scan mutants
dc.description.keywords Bioinsecticide
dc.description.keywords BKCa channel
dc.description.keywords Cockroach neurons
dc.description.keywords Kappa-atracotoxin
dc.staffid 870145 en_US
pubs.embargo.period Not known
pubs.organisational-group /University of Technology Sydney
pubs.organisational-group /University of Technology Sydney/Faculty of Science
pubs.organisational-group /University of Technology Sydney/Strength - Health Technologies


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