Instituto de Biotecnología, Universidad Nacional Autónoma de México, Av. Universidad 2001, Col. Chamilpa, Cuernavaca, Morelos, CP. 62210, Mexico.
Toxins (Basel). 2014 Jan 17;6(1):359-70. doi: 10.3390/toxins6010359.
In this work, we have examined the neuromuscular activity of Micrurus laticollaris (Mexican coral snake) venom (MLV) in vertebrate isolated nerve-muscle preparations. In chick biventer cervicis preparations, the MLV induced an irreversible concentration- and time-dependent (1-30 µg/mL) neuromuscular blockade, with 50% blockade occurring between 8 and 30 min. Muscle contractures evoked by exogenous acetylcholine were completely abolished by MLV, whereas those of KCl were also significantly altered (86% ± 11%, 53% ± 11%, 89% ± 5% and 89% ± 7% for one, three, 10 and 30 µg of venom/mL, respectively; n = 4; p < 0.05). In mouse phrenic nerve-diaphragm preparations, MLV (1-10 µg/mL) promoted a slight increase in the amplitude of twitch-tension (3 µg/mL), followed by neuromuscular blockade (n = 4); the highest concentration caused complete inhibition of the twitches (time for 50% blockade = 26 ± 3 min), without exhibiting a previous neuromuscular facilitation. The venom (3 µg/mL) induced a biphasic modulation in the frequency of miniature end-plate potentials (MEPPs)/min, causing a significant increase after 15 min, followed by a decrease after 60 min (from 17 ± 1.4 (basal) to 28 ± 2.5 (t15) and 12 ± 2 (t60)). The membrane resting potential of mouse diaphragm preparations pre-exposed or not to d-tubocurarine (5 µg/mL) was also significantly less negative with MLV (10 µg/mL). Together, these results indicate that M. laticollaris venom induces neuromuscular blockade by a combination of pre- and post-synaptic activities.
在这项工作中，我们检查了 Micrurus laticollaris（墨西哥珊瑚蛇）毒液（MLV）在脊椎动物离体神经-肌肉制剂中的神经肌肉活性。在小鸡双腹颈制剂中，MLV 诱导了一种不可逆的浓度和时间依赖性（1-30 µg/mL）的神经肌肉阻滞，50%的阻滞发生在 8-30 分钟之间。MLV 完全消除了外源性乙酰胆碱引起的肌肉收缩，而 KCl 引起的肌肉收缩也发生了显著改变（分别为 1、3、10 和 30 µg/mL 时为 86%±11%、53%±11%、89%±5%和 89%±7%；n=4；p<0.05）。在小鼠膈神经-膈肌制剂中，MLV（1-10 µg/mL）轻微增加了颤搐张力的幅度（3 µg/mL），随后发生神经肌肉阻滞（n=4）；最高浓度导致抽搐完全抑制（50%阻滞时间=26±3 分钟），而没有表现出先前的神经肌肉易化。毒液（3 µg/mL）在微小终板电位（MEPPs）/min 的频率上引起双相调制，在 15 分钟后引起显著增加，然后在 60 分钟后减少（从 17±1.4（基础）到 28±2.5（t15）和 12±2（t60））。未预先暴露于 d-筒箭毒碱（5 µg/mL）或预先暴露于 d-筒箭毒碱的小鼠膈肌制剂的膜静息电位也明显更负，用 MLV（10 µg/mL）处理。综上所述，这些结果表明，M. laticollaris 毒液通过前突触和后突触活动的结合诱导神经肌肉阻滞。
