Modification of synaptic transmission and sodium channel inactivation by the insect-selective scorpion toxin LqhαIT
Modification of synaptic transmission and sodium channel inactivation by the insect-selective scorpion toxin LqhαIT
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DOI：
10.1152/jn.2000.83.3.1181
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发表时间：
2000-03-01
影响因子：
2.5
通讯作者：
Adams, ME
中科院分区：
文献类型：
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作者：
Lee, D;Gurevitz, M;Adams, ME
肽Lqh α IT是一种α蝎毒素，对昆虫钠通道比哺乳动物通道具有显著的选择性。我们在家蝇（Musca domestica）中检查了Lqh α it诱导的麻痹症状及其神经生理学相关因素。将LqhaIT注射到蝇幼虫体内会产生过度活跃，其特征是全身持续、不规则的肌肉抽搐。这些症状与毒素的两种生理效应引起的运动单位兴奋性升高有关：1)增加递质释放和2)运动神经的重复动作电位。随着神经诱发的突触电流的增加，递质释放明显增加，这与神经末梢松散斑块记录中动作电位相关电流（APAC）持续时间的增加有关。重复APACs侵袭神经末梢。该毒素对果蝇中枢神经元钠电流失活产生明显的抑制作用，这可以解释APAC持续时间延长和神经肌肉连接处神经递质释放升高的原因。稳态失活明显转移到更多的正电位，而电压依赖性通道的激活不受影响。稳态失活的转变提供了一种诱导运动神经元重复活动的机制。LqhaIT对运动神经末梢钠通道失活的影响解释了受影响昆虫的递质释放增加和重复活动导致的过度活跃。
The peptide Lqh alpha IT is an alpha-scorpion toxin that shows significant selectivity for insect sodium channels over mammalian channels. We examined the symptoms of Lqh alpha IT-induced paralysis and its neurophysiological correlates in the house fly (Musca domestica). Injection of LqhaIT into fly larvae produced hyperactivity characterized by continuous, irregular muscle twitching throughout the body. These symptoms were correlated with elevated excitability in motor units caused by two physiological effects of the toxin: 1) increased transmitter release and 2) repetitive action potentials in motor nerves. Increased transmitter release was evident as augmentation of neurally evoked synaptic current, and this was correlated with an increased duration of action potential-associated current (APAC) in loose patch recordings from nerve terminals. Repetitive APACs were observed to invade nerve endings. The toxin produced marked inhibition of sodium current inactivation in fly central neurons, which can account for increased duration of the APAC: and elevated neurotransmitter release at the neuromuscular junction. Steady-state inactivation was shifted significantly to more positive potentials, whereas voltage-dependent activation of the channels was not affected. The shift in steady-state inactivation provides a mechanism for inducing repetitive activity in motoneurons. The effects of LqhaIT on sodium channel inactivation in motor nerve endings call account both for increased transmitter release and repetitive activity leading to hyperactivity in affected insects.