The omega-atracotoxins: selective blockers of insect M-LVA and HVA calcium channels.

The omega-atracotoxins: selective blockers of insect M-LVA and HVA calcium channels. Research Abstract Details 

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The omega-atracotoxins: selective blockers of insect M-LVA and HVA calcium channels. Abstract Text:

Youmie Chong,Jessica L Hayes,Brianna Sollod,Suping Wen,David T Wilson,Peter G Hains,Wayne C Hodgson,Kevin W Broady,Glenn F King,Graham M Nicholson,

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.

The omega-atracotoxins: selective blockers of insect M-LVA and HVA calcium channels. Publishing Authors By Initials

Y Chong,JL Hayes,B Sollod,S Wen,DT Wilson,PG Hains,WC Hodgson,KW Broady,GF King,GM Nicholson,

For similar urogenital system: genitalia: genitalia, male: vas deferens research abstracts see: urogenital system: genitalia: genitalia, male: vas deferens research

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The omega-atracotoxins: selective blockers of insect M-LVA and HVA calcium channels. Journal Published:

PUBLICATION TYPE: Research Support, U.S. Gov't,

Journal: Biochemical pharmacology

VOLUME: 74

Page Numbers: 623-38

Journal Abbreviation: Biochem. Pharmacol.

ISSN: 0006-2952

DAY: 25

MONTH: 05

YEAR: 2007

The omega-atracotoxins: selective blockers of insect M-LVA and HVA calcium channels. Information

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LANGUAGE: eng

NlmUniqueID: 101032

The omega-atracotoxins: selective blockers of insect M-LVA and HVA calcium channels. Keywords Mesh Terms:

KEYWORDS: Vas Deferens

MESH TERMS: pathology

Chemical & Substance for Abstract: The omega-atracotoxins: selective blockers of insect M-LVA and HVA calcium channels. Information

Substance Name: Spider Venoms

Registry Number: 0

Grant and Affiliation Information for The omega-atracotoxins: selective blockers of insect M-LVA and HVA calcium channels.

AFFILIATION: Neurotoxin Research Group, Department of Medical & Molecular Biosciences, University of Technology, Sydney, Broadway, NSW 2007, Australia.

Country: England

AGENCY: United States NCCDPHP

GRANT: DP0559396

ACRONYM: DP

MEDLINETA: Biochem Pharmacol

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