Kalapothakis Evanguedes, Kushmerick Christopher, Gusmão Daniel R, Favaron Guilherme O C, Ferreira Anderson J, Gomez Marcus V, Pinto de Almeida Alvair
Departamento de Farmacologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av. Antonio Carlos 6627, Pampulha, 31270-901, MG, Belo Horizonte, Brazil.
Toxicon. 2003 Jan;41(1):23-8. doi: 10.1016/s0041-0101(02)00204-0.
We studied the effect of the venom of the Brazilian spider, Lasiodora sp. (Mygalomorphae, Theraphosidae), on force generation and electrical activity in the isolated rat heart. Previous work showed that this venom is excitotoxic to excitable cells due to Na(+) channel gating modifier activity [Toxicon 39 (2001) 991]. In the isolated heart, the venom (10-100 microg bolus administration) caused a dose-dependent bradycardia, with transient cardiac arrest and rhythm disturbances. The electrocardiogram showed that the reduction of heart rate was due to sinus bradycardia, sinus arrest and partial or complete A-V block. All of the effects were reversible upon washout of the venom. The effect of the venom was potentiated by the anticholinesterase neostigmine (3.3 microM), suppressed by the muscarinic acetylcholine receptor antagonist atropine (1.4 microM), and inhibited by the vesicular acetylcholine transporter inhibitor (-)-vesamicol (10 microM). Tetrodotoxin (200 nM) did not inhibit the effect of the venom. Together, these data suggest that this Lasiodora venom evokes vesicular release of acetylcholine from parasympathetic nerve terminals by activating tetrodotoxin-resistant Na(+) channels.
我们研究了巴西蜘蛛Lasiodora sp.（原蛛亚目，捕鸟蛛科）的毒液对离体大鼠心脏的力产生和电活动的影响。先前的研究表明，由于钠通道门控修饰活性，这种毒液对可兴奋细胞具有兴奋性毒性作用【《毒理学》39 (2001) 991】。在离体心脏中，毒液（10 - 100微克推注给药）引起剂量依赖性心动过缓，伴有短暂心脏停搏和节律紊乱。心电图显示心率降低是由于窦性心动过缓、窦性停搏以及部分或完全性房室传导阻滞。毒液冲洗后，所有这些效应均可逆转。抗胆碱酯酶新斯的明（3.3微摩尔）可增强毒液的作用，毒蕈碱型乙酰胆碱受体拮抗剂阿托品（1.4微摩尔）可抑制其作用，囊泡型乙酰胆碱转运体抑制剂（-）-vesamicol（10微摩尔）也可抑制其作用。河豚毒素（200纳摩尔）不抑制毒液的作用。总之，这些数据表明，这种Lasiodora毒液通过激活对河豚毒素不敏感的钠通道，引发副交感神经末梢乙酰胆碱的囊泡释放。
