Barber Carmel M, Rusmili Muhamad Rusdi Ahmad, Hodgson Wayne C
Monash Venom Group, Department of Pharmacology, Monash University, Clayton, VIC 3168, Australia.
Department of Basic Medical Sciences, Kulliyyah of Pharmacy, International Islamic University Malaysia, Bandar Indera Mahkota 23800, Malaysia.
Toxins (Basel). 2016 Feb 29;8(3):58. doi: 10.3390/toxins8030058.
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.
太攀蛇（澳大拉西亚太攀蛇属）是眼镜蛇科动物，其毒液毒性极强，含有突触前（β）和突触后（α）神经毒素。澳大拉西亚太攀蛇属的新成员——西部沙漠太攀蛇，其毒液已被证明具有显著的体外神经毒性。目前尚未从这种毒液中分离出任何成分。我们描述了一种短链突触后神经毒素——α-澳大拉西亚太攀蛇毒素-Ot1a（α-EPTX-Ot1a；6712道尔顿）的特性，它约占西部沙漠太攀蛇毒液的30%。在鸡双头肌颈神经-肌肉标本中，α-澳大拉西亚太攀蛇毒素-Ot1a（0.1-1微摩尔/升）产生浓度依赖性间接收缩抑制作用，并消除了对外源性乙酰胆碱和卡巴胆碱的收缩反应。α-澳大拉西亚太攀蛇毒素-Ot1a（1微摩尔/升）对间接收缩的抑制作用不能通过冲洗组织来逆转。预先加入太攀蛇抗蛇毒血清（10单位/毫升）可延迟α-澳大拉西亚太攀蛇毒素-Ot1a（1微摩尔/升）的神经毒性作用，并显著减弱α-澳大拉西亚太攀蛇毒素-Ot1a（0.1微摩尔/升）的神经毒性作用。α-澳大拉西亚太攀蛇毒素-Ot1a对卡巴胆碱浓度-反应曲线表现出拟不可逆拮抗作用，pA₂值为8.02±0.05。从头测序揭示了短链突触后神经毒素（即α-澳大拉西亚太攀蛇毒素-Ot1a）的主要序列以及在西部沙漠太攀蛇毒液中发现的其他三种同工型。α-澳大拉西亚太攀蛇毒素-Ot1a与其他太攀蛇短链突触后神经毒素具有高度的序列相似性（即>87%）。
