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

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Show simple item record Gunning, Simon en_US Maggio, Francesco en_US Windley, Monique en_US Valenzuela, Stella en_US King, Glenn en_US Nicholson, Graham en_US
dc.contributor.editor en_US 2010-05-28T09:45:48Z 2010-05-28T09:45:48Z 2008 en_US
dc.identifier 2007002576 en_US
dc.identifier.citation Gunning Simon et al. 2008, 'The Janus-faced atracotoxins are specific blockers of invertebrate K(Ca) channels', Blackwell Publishing Inc., vol. 275, no. 16, pp. 4045-4059. en_US
dc.identifier.issn 1742-464X en_US
dc.identifier.other C1 en_US
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 calcium activated K+ (KCa) channels. 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 potassium (KV), calcium (CaV), or sodium (NaV) channel subtypes. J ACTX-Hv1c blocked heterologously expressed cockroach BKCa (pSlo) channels without a significant shift in the voltage-dependence of activation. However, the block was voltage-dependent, indicating that the toxin likely 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 I?M) and its lack of activity on rat dorsal root ganglion neuron IK(Ca). This study establishes the Janus-faced atracotoxins as valuable tools for the study of invertebrate KCa channels and suggests that KCa channels might be a potential insecticide target. en_US
dc.language en_US
dc.publisher Blackwell Publishing Inc. en_US
dc.relation.isbasedon en_US
dc.title The Janus-faced atracotoxins are specific blockers of invertebrate K(Ca) channels en_US
dc.parent FEBS Journal en_US
dc.journal.volume 275 en_US
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 SCI.Medical and Molecular Biosciences en_US
dc.conference Verified OK en_US
dc.for 110100 en_US
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 Medical Biochemistry and Metabolomics en_US
dc.classification.type FOR-08 en_US
dc.edition en_US
dc.custom en_US en_US
dc.location.activity ISI:000257988000008 en_US
dc.description.keywords alaine-scan mutants; bioinsecticide; BKCa channel; cockroach neurons; kappaatracotoxin en_US
dc.staffid 870145 en_US

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