Chong, Youmie, Hayes, Jessica L., Sollod, Brianna, Wen, Suping, Wilson, David T., Hains, Peter G., Hodgson, Wayne C., Broady, Kevin W., King, Glenn F., and Nicholson, Graham M . (2007) The omega-atracotoxins: selective blockers of insect M-LVA and HVA calcium channels. Biochemical Pharmacology, 74 (4). pp. 623-638.

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Abstract

The omega-atracotoxins (omega-ACTX) are a family of arthropod-selective peptide neurotoxins from Australian funnel-web spider venoms (Hexathelidae: Atracinae) that are candidates for development as biopesticides. We isolated a 37-residue insect-selective neurotoxin, omega-ACTX-Ar1a, from the venom of the Sydney funnel-web spider Atrax robustus, with high homology to several previously characterized members of the omega-ACTX-1 family. The peptide induced potent excitatory symptoms, followed by flaccid paralysis leading to death, in acute toxicity tests in house crickets. Using isolated smooth and skeletal nerve-muscle preparations, the toxin was shown to lack overt vertebrate toxicity at concentrations up to 1 microM. To further characterize the target of the omega-ACTXs, voltage-clamp analysis using the whole-cell patch-clamp technique was undertaken using cockroach dorsal unpaired median neurons. It is shown here for the first time that omega-ACTX-Ar1a, and its homolog omega-ACTX-Hv1a from Hadronyche versuta, reversibly block both mid-low- (M-LVA) and high-voltage-activated (HVA) insect calcium channel (Ca(v)) currents. This block occurred in the absence of alterations in the voltage-dependence of Ca(v) channel activation, and was voltage-independent, suggesting that omega-ACTX-1 family toxins are pore blockers rather than gating modifiers. At a concentration of 1 microM omega-ACTX-Ar1a failed to significantly affect global K(v) channel currents. However, 1 microM omega-ACTX-Ar1a caused a modest 18% block of insect Na(v) channel currents, similar to the minor block of Na(v) channels reported for other insect Ca(v) channel blockers such as omega-agatoxin IVA. These findings validate both M-LVA and HVA Ca(v) channels as potential targets for insecticides.

Item ID:	39025
Item Type:	Article (Research - C1)
ISSN:	1873-2968
Keywords:	ω-ACTX-Ar1a; ω-ACTX-Hv1a; ω-Atracotoxin; voltage-gated calcium channel; insecticide; Atrax robustus
Funders:	Australian Research Council (ARC), National Science Foundation (NSF)
Projects and Grants:	ARC Discovery grant DP0559396, NSF grant MCB0234638
Date Deposited:	23 Jun 2015 23:20
FoR Codes:	03 CHEMICAL SCIENCES > 0304 Medicinal and Biomolecular Chemistry > 030406 Proteins and Peptides @ 100%
SEO Codes:	97 EXPANDING KNOWLEDGE > 970106 Expanding Knowledge in the Biological Sciences @ 100%
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