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Defining the role of post-synaptic α-neurotoxins in paralysis due to snake envenoming in humans.
Cell Mol Life Sci 2018; 75(23):4465-4478CM

Abstract

Snake venom α-neurotoxins potently inhibit rodent nicotinic acetylcholine receptors (nAChRs), but their activity on human receptors and their role in human paralysis from snakebite remain unclear. We demonstrate that two short-chain α-neurotoxins (SαNTx) functionally inhibit human muscle-type nAChR, but are markedly more reversible than against rat receptors. In contrast, two long-chain α-neurotoxins (LαNTx) show no species differences in potency or reversibility. Mutant studies identified two key residues accounting for this. Proteomic and clinical data suggest that paralysis in human snakebites is not associated with SαNTx, but with LαNTx, such as in cobras. Neuromuscular blockade produced by both subclasses of α-neurotoxins was reversed by antivenom in rat nerve-muscle preparations, supporting its effectiveness in human post-synaptic paralysis.

Authors+Show Affiliations

Monash Venom Group, Department of Pharmacology, Biomedicine Discovery Institute, Monash University, Clayton, VIC, 3800, Australia. Faculty of Medicine and Allied Sciences, Rajarata University of Sri Lanka, Saliyapura, 50008, Sri Lanka.School of Biomedical Sciences, University of Queensland, St. Lucia, QLD, 4072, Australia. Institute of Molecular Bioscience, University of Queensland, St. Lucia, QLD, 4072, Australia.School of Biomedical Sciences, University of Queensland, St. Lucia, QLD, 4072, Australia. l.rash@uq.edu.au. Institute of Molecular Bioscience, University of Queensland, St. Lucia, QLD, 4072, Australia. l.rash@uq.edu.au.Monash Venom Group, Department of Pharmacology, Biomedicine Discovery Institute, Monash University, Clayton, VIC, 3800, Australia. wayne.hodgson@monash.edu.Monash Venom Group, Department of Pharmacology, Biomedicine Discovery Institute, Monash University, Clayton, VIC, 3800, Australia. geoff.isbister@gmail.com. Clinical Toxicology Research Group, University of Newcastle, Callaghan, NSW, 2308, Australia. geoff.isbister@gmail.com.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30069700

Citation

Silva, Anjana, et al. "Defining the Role of Post-synaptic Α-neurotoxins in Paralysis Due to Snake Envenoming in Humans." Cellular and Molecular Life Sciences : CMLS, vol. 75, no. 23, 2018, pp. 4465-4478.
Silva A, Cristofori-Armstrong B, Rash LD, et al. Defining the role of post-synaptic α-neurotoxins in paralysis due to snake envenoming in humans. Cell Mol Life Sci. 2018;75(23):4465-4478.
Silva, A., Cristofori-Armstrong, B., Rash, L. D., Hodgson, W. C., & Isbister, G. K. (2018). Defining the role of post-synaptic α-neurotoxins in paralysis due to snake envenoming in humans. Cellular and Molecular Life Sciences : CMLS, 75(23), pp. 4465-4478. doi:10.1007/s00018-018-2893-x.
Silva A, et al. Defining the Role of Post-synaptic Α-neurotoxins in Paralysis Due to Snake Envenoming in Humans. Cell Mol Life Sci. 2018;75(23):4465-4478. PubMed PMID: 30069700.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Defining the role of post-synaptic α-neurotoxins in paralysis due to snake envenoming in humans. AU - Silva,Anjana, AU - Cristofori-Armstrong,Ben, AU - Rash,Lachlan D, AU - Hodgson,Wayne C, AU - Isbister,Geoffrey K, Y1 - 2018/08/01/ PY - 2018/05/15/received PY - 2018/07/26/accepted PY - 2018/07/21/revised PY - 2018/8/3/pubmed PY - 2018/11/6/medline PY - 2018/8/3/entrez KW - Neurotoxicity KW - Nicotinic acetylcholine receptor KW - Paralysis KW - Snakebite KW - α-Neurotoxins SP - 4465 EP - 4478 JF - Cellular and molecular life sciences : CMLS JO - Cell. Mol. Life Sci. VL - 75 IS - 23 N2 - Snake venom α-neurotoxins potently inhibit rodent nicotinic acetylcholine receptors (nAChRs), but their activity on human receptors and their role in human paralysis from snakebite remain unclear. We demonstrate that two short-chain α-neurotoxins (SαNTx) functionally inhibit human muscle-type nAChR, but are markedly more reversible than against rat receptors. In contrast, two long-chain α-neurotoxins (LαNTx) show no species differences in potency or reversibility. Mutant studies identified two key residues accounting for this. Proteomic and clinical data suggest that paralysis in human snakebites is not associated with SαNTx, but with LαNTx, such as in cobras. Neuromuscular blockade produced by both subclasses of α-neurotoxins was reversed by antivenom in rat nerve-muscle preparations, supporting its effectiveness in human post-synaptic paralysis. SN - 1420-9071 UR - https://www.unboundmedicine.com/medline/citation/30069700/Defining_the_role_of_post_synaptic_α_neurotoxins_in_paralysis_due_to_snake_envenoming_in_humans_ L2 - https://dx.doi.org/10.1007/s00018-018-2893-x DB - PRIME DP - Unbound Medicine ER -