Isolation and Pharmacological Characterization of α-Elapitoxin-Ot1a, a Short-Chain Postsynaptic Neurotoxin from the Venom of the Western Desert Taipan, Oxyuranus temporalis.

Carmel Barber,Wayne Hodgson,Muhamad Ahmad Rusmili

doi:10.3390/toxins8030058

Carmel Barber, Wayne Hodgson + Show 1 more

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https://doi.org/10.3390/toxins8030058

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Abstract

Taipans (Oxyuranus spp.) are elapids with highly potent venoms containing presynaptic (β) and postsynaptic (α) neurotoxins. O. temporalis (Western Desert taipan), a newly discovered member of this genus, has been shown to possess venom which displays marked in vitro neurotoxicity. No components have been isolated from this venom. We describe the characterization of α-elapitoxin-Ot1a (α-EPTX-Ot1a; 6712 Da), a short-chain postsynaptic neurotoxin, which accounts for approximately 30% of O. temporalis venom. α-Elapitoxin-Ot1a (0.1–1 µM) produced concentration-dependent inhibition of indirect-twitches, and abolished contractile responses to exogenous acetylcholine and carbachol, in the chick biventer cervicis nerve-muscle preparation. The inhibition of indirect twitches by α-elapitoxin-Ot1a (1 µM) was not reversed by washing the tissue. Prior addition of taipan antivenom (10 U/mL) delayed the neurotoxic effects of α-elapitoxin-Ot1a (1 µM) and markedly attenuated the neurotoxic effects of α-elapitoxin-Ot1a (0.1 µM). α-Elapitoxin-Ot1a displayed pseudo-irreversible antagonism of concentration-response curves to carbachol with a pA2 value of 8.02 ± 0.05. De novo sequencing revealed the main sequence of the short-chain postsynaptic neurotoxin (i.e., α-elapitoxin-Ot1a) as well as three other isoforms found in O. temporalis venom. α-Elapitoxin-Ot1a shows high sequence similarity (i.e., >87%) with other taipan short-chain postsynaptic neurotoxins.

Highlights

The Oxyuranus genus consists of three species of highly venomous Australo-Papuan elapids; i.e., inland taipan (O. microlepidotus), coastal taipan
Snake venoms are comprised of numerous components
We have recently studied studied O. temporalis venom and shown that the reverse‐phase high-performance liquid chromatography (HPLC) venom profile consists of only temporalis andmajor shownpeak that the reverse-phase profile consists only a fewin peaks a few peaksvenom with the eluting around 15 minvenom

Summary

Introduction

New Guinea) and the more recently discovered O. temporalis (Western Desert taipan, [1]). We recently showed that O. temporalis venom displays marked post-synaptic neurotoxic activity in isolated skeletal muscle [4]. Taipan venoms contain presynaptic and postsynaptic neurotoxins and have been shown to contain natriuretic-like peptides [5,6], prothrombin activators [6,7,8,9], reversible calcium channels blockers (i.e., taicatoxin, [6,10]), cysteine-rich secretory proteins (CRISP) [6] and Kunitz-type plasma kallikrein inhibitors [6,11]. The presynaptic neurotoxins isolated from taipan venoms are Toxins 2016, 8, 58; doi:10.3390/toxins8030058 www.mdpi.com/journal/toxins paradoxin (O. microlepidotus, [12]), taipoxin (O. scutellatus, [13]) and cannitoxin The presynaptic neurotoxins isolated from taipan venoms are Toxins 2016, 8, 58; doi:10.3390/toxins8030058 www.mdpi.com/journal/toxins paradoxin (O. microlepidotus, [12]), taipoxin (O. scutellatus, [13]) and cannitoxin (O. s. canni, [14]), each (α, ββ and and γ) γ) with withmolecular molecularmasses massesbetween between4545and and4747kDa kDa[12,13,14,15]. [12,13,14,15].

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