Novel neurotoxic activity in calliophis intestinalis venom

Dashevsky, Daniel and Deuis, Jennifer R. and Vetter, Irina and Huynh, Tam and Hodgson, Wayne C. and Tan, Choo Hock and Nouwens, Amanda and Fry, Bryan G. (2022) Novel neurotoxic activity in calliophis intestinalis venom. Neurotoxicity Research, 40 (1). pp. 173-178. ISSN 1029-8428, DOI

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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 (Na-V) 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 Na-V channel antagonist-the first known from a vertebrate venom-by decreasing the peak current of Na(V)1.4 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 A(2)s, snake venom metalloproteases, and vespryns. Some of the three-finger toxins are similar to the delta-elapitoxins from the venom of the closely related Calliophis bivirgatus. However, delta-elapitoxins act as Na-V channel agonists in C. bivirgatus whereas C. intestinalis venom contains Na-V channel antagonists. The toxins and mechanisms responsible for the neuromuscular symptoms remain unclear as does the identity of the Na-V channel antagonists. These aspects of this unusual venom require further study.

Item Type: Article
Funders: UQ Centennial Scholarship from The University of Queensland, Australian Government Department of Industry, Innovation and Science, CSIRO Early Research Career Postdoctoral Fellowship from the Commonwealth Science & Industry Research Organisation, National Health and Medical Research Council (NHMRC) of Australia [Grant No: APP1162503& APP1139961 & 1110343], Australian Research Council [Grant No: DP210102406]
Uncontrolled Keywords: Elapid; Coral snake; Patch clamp; Venomics; Snakebite
Subjects: R Medicine > RC Internal medicine
R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Divisions: Faculty of Medicine
Depositing User: Ms. Juhaida Abd Rahim
Date Deposited: 19 Jul 2022 10:46
Last Modified: 19 Jul 2022 10:46

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