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 nerve-evoked 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.
St Pierre
L
L
The Queensland Cancer Fund Research Unit, The Queensland Institute of Medical Research, P.O. Box Royal Brisbane Hospital, Herston, Brisbane, 4029, Australia.
Fischer
H
H
Adams
D J
DJ
Schenning
M
M
Lavidis
N
N
de Jersey
J
J
Masci
P P
PP
Lavin
M F
MF
D000595:Amino Acid Sequence; D000818:Animals; D001315:Australia; D001483:Base Sequence; D002024:Bufo marinus; D017931:DNA Primers / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D004546:Elapid Venoms / Q000235:genetics / Q000302:isolation & purification / Q000633:toxicity*; D017815:Elapidae / Q000235:genetics; D004594:Electrophysiology; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D009498:Neurotoxins / Q000235:genetics / Q000302:isolation & purification / Q000633:toxicity*; D018733:Nicotinic Antagonists / Q000302:isolation & purification / Q000633:toxicity; D011978:Receptors, Nicotinic / Q000187:drug effects* / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000633:toxicity; D017386:Sequence Homology, Amino Acid
D017931:DNA Primers; D018076:DNA, Complementary; D004546:Elapid Venoms; D009498:Neurotoxins; D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; D011994:Recombinant Proteins