Analysis of the action of lidocaine on insect sodium channels.
Analysis of the action of lidocaine on insect sodium channels.
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DOI：
10.1016/j.ibmb.2010.09.010
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发表时间：
2011-01
影响因子：
3.8
通讯作者：
Dong, Ke
中科院分区：
文献类型：
--
作者：
Song, Weizhong;Silver, Kristopher S.;Du, Yuzhe;Liu, Zhiqi;Dong, Ke
一类新的钠通道阻断剂杀虫剂（SCBI），其包括茚虫威、其活性代谢物、DCJW和氰氟虫腙，优选以与局部麻醉（LA）药物阻断哺乳动物钠通道的方式类似的方式阻断昆虫和哺乳动物钠通道的失活状态。最近的一项研究表明，蟑螂钠通道中的两个残基，F1817和Y1824，对应于哺乳动物钠通道中鉴定的两个关键LA相互作用残基，对于SCBI对昆虫钠通道的作用并不重要，这表明SCBI与昆虫钠通道的独特相互作用。然而，LAs对昆虫钠通道的作用机制尚未研究。在这项研究中，我们研究了利多卡因对蟑螂钠通道变体BgNav 1 -1a的影响，并确定F1817和Y1824是否也对LA对昆虫钠通道的作用至关重要。利多卡因在静息状态下阻断BgNav 1 -1a通道，其效力与在哺乳动物钠通道中观察到的效力相似。利多卡因还稳定了BgNav 1 -1a通道的快速失活和缓慢失活状态，并引起有限程度的使用和频率依赖性阻滞，这是LA对哺乳动物钠通道作用的主要特征。F1817和Y1824的丙氨酸取代降低了BgNav 1 -1a通道对利多卡因使用依赖性阻滞的敏感性，但对利多卡因的强直阻滞和失活稳定作用无影响。因此，类似于哺乳动物钠通道，F1817和Y1824对于利多卡因对蟑螂钠通道的作用是重要的。我们的研究结果表明，利多卡因和SCBI的受体网站是不同的昆虫钠通道。
A new class of sodium channel blocker insecticides (SCBIs), which include indoxacarb, its active metabolite, DCJW, and metaflumizone, preferably block inactivated states of both insect and mammalian sodium channels in a manner similar to that by which local anesthetic (LA) drugs block mammalian sodium channels. A recent study showed that two residues in the cockroach sodium channel, F1817 and Y1824, corresponding to two key LA-interacting residues identified in mammalian sodium channels are not important for the action of SCBIs on insect sodium channels, suggesting unique interactions of SCBIs with insect sodium channels. However, the mechanism of action of LAs on insect sodium channels has not been investigated. In this study, we examined the effects of lidocaine on a cockroach sodium channel variant, BgNav1-1a, and determined whether F1817 and Y1824 are also critical for the action of LAs on insect sodium channels. Lidocaine blocked BgNav1-1a channels in the resting state with potency similar to that observed in mammalian sodium channels. Lidocaine also stabilized both fast-inactivated and slow-inactivated states of BgNav1-1a channels, and caused a limited degree of use- and frequency-dependent block, major characteristics of LA action on mammalian sodium channels. Alanine substitutions of F1817 and Y1824 reduced the sensitivity of the BgNav1-1a channel to the use-dependent block by lidocaine, but not to tonic blocking and inactivation stabilizing effects of lidocaine. Thus, similar to those on mammalian sodium channels, F1817 and Y1824 are important for the action of lidocaine on cockroach sodium channels. Our results suggest that the receptor sites for lidocaine and SCBIs are different on insect sodium channels.
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