Distinct activities of novel neurotoxins from Australian venomous snakes for nicotinic acetylcholine receptors

Envenomation from Australian elapid snakes results in a myriad of neurological effects due to post-synaptic neurotoxins that bind and inhibit nicotinic acetylcholine receptors (nAChRs) of neurons and muscle fibres. However, despite the significant physiological effects of these toxins, they have remained largely undercharacterised at the molecular level. This study describes the identification and comparative analysis of multiple neurotoxin isoforms from ten Australian snakes, including functional characterisation of two of these isoforms, Os SNTX-1 from Oxyuranus scutellatus and the more potent Pt LNTX-1 from Pseudonaja textilis. Electrophysiological recordings from adrenal chromaffin cells demonstrate that both neurotoxins act as competitive antagonists of nAChRs in a concentration-dependent manner. Their effects upon spontaneous and nerveevoked membrane responses at the amphibian neuromuscular junction provide further evidence that both toxins bind muscle nAChRs in an irreversible manner. This study represents one of the most comprehensive descriptions to date of the sequences and activity of individual Australian elapid neurotoxins.

Authors and Affiliations

1. The Queensland Cancer Fund Research Unit, The Queensland Institute of Medical Research, Royal Brisbane Hospital, Herston, Brisbane, 4029, Australia

   L. St Pierre & M. F. Lavin

2. Faculty of Health Sciences, University of Queensland, Brisbane, QLD, 4072, Australia

   L. St Pierre, P. P. Masci & M. F. Lavin

3. School of Biomedical Sciences, University of Queensland, Brisbane, QLD, 4072, Australia

   H. Fischer, D. J. Adams, M. Schenning & N. Lavidis

4. Faculty of Biological and Chemical Sciences, University of Queensland, Brisbane, QLD, 4072, Australia

   J. de Jersey

Corresponding author

Correspondence to M. F. Lavin.

Received 2 August 2007; received after revision 6 September 2007; accepted 10 September 2007

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