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Novel Neurotoxic Activity in Calliophis intestinalis Venom

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Abstract

In this work, we investigated the in vitro neurotoxicity of Calliophis intestinalis venom using chick biventer cervicis neuromuscular preparations and electrophysiological analysis of voltage-gated sodium (NaV) channels expressed in HEK293 cells. We found that the indirect twitches of the neuromuscular preparations decreased over time when exposed to venom. However, the responses of these preparations to the agonists acetylcholine, carbachol, and potassium chloride were not changed after incubation with the venom. Our electrophysiological experiments show that C. intestinalis venom acts as a NaV channel antagonist—the first known from a vertebrate venom—by decreasing the peak current of NaV1.4 channels without changing the kinetics of activation or inactivation. Our proteomic results accord with earlier analyses and find that the venom contains three-finger toxins, cysteine-rich secretory proteins, kunitz peptides, phospholipase A2s, snake venom metalloproteases, and vespryns. Some of the three-finger toxins are similar to the δ-elapitoxins from the venom of the closely related Calliophis bivirgatus. However, δ-elapitoxins act as NaV channel agonists in C. bivirgatus whereas C. intestinalis venom contains NaV channel antagonists. The toxins and mechanisms responsible for the neuromuscular symptoms remain unclear as does the identity of the NaV channel antagonists. These aspects of this unusual venom require further study.

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Funding

DD was funded by a UQ Centennial Scholarship from The University of Queensland, a Research Training Program scholarship from the Australian Government Department of Education and Training, and a CSIRO Early Research Career Postdoctoral Fellowship from the Commonwealth Science & Industry Research Organisation. J.R.D and I.V. are supported by NHMRC fellowships APP1162503 and APP1139961 (J.R.D.). T.M.H. was supported by a PhD scholarship funded from an Australian National Health and Medical Research Council (NHMRC) Centres for Research Excellence Grant (ID:1110343). BGF was funded by Australian Research Council Grant DP210102406.

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Author notes

  1. Daniel Dashevsky

    Present address: Australian National Insect Collection, Commonwealth Science and Industry Research Organization, Canberra, ACT 2601, Australia

Authors and Affiliations

  1. Venom Evolution Lab, School of Biological Sciences, University of Queensland, St Lucia, QLD 4072, Australia

    Daniel Dashevsky & Bryan G. Fry

  2. Institute for Molecular Bioscience, The University of Queensland, St Lucia, QLD 4072, Australia

    Jennifer R. Deuis & Irina Vetter

  3. School of Pharmacy, The University of Queensland, Woolloongabba, QLD 4102, Australia

    Irina Vetter

  4. Department of Pharmacology, Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia

    Tam Huynh & Wayne C. Hodgson

  5. Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur, 50603, Malaysia

    Choo Hock Tan

  6. School of Chemistry and Molecular Biosciences, University of Queensland, St Lucia, QLD 4072, Australia

    Amanda Nouwens

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  1. Daniel Dashevsky
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  2. Jennifer R. Deuis
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  8. Bryan G. Fry
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Corresponding author

Correspondence to Bryan G. Fry.

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Ethics approval

Chick biventer cervicis experiments were carried out under Monash University Animal Ethics Committee application number 2257, approved on 18 December 2019.

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Dashevsky, D., Deuis, J.R., Vetter, I. et al. Novel Neurotoxic Activity in Calliophis intestinalis Venom. Neurotox Res 40, 173–178 (2022). https://doi.org/10.1007/s12640-021-00413-2

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