ELECTROPHYSIOLOGICAL IDENTIFICATION OF SITE-INSENSITIVE MECHANISMS IN KNOCKDOWN-RESISTANT STRAINS (KDR, SUPER-KDR) OF THE HOUSEFLY LARVA (MUSCA-DOMESTICA)
ELECTROPHYSIOLOGICAL IDENTIFICATION OF SITE-INSENSITIVE MECHANISMS IN KNOCKDOWN-RESISTANT STRAINS (KDR, SUPER-KDR) OF THE HOUSEFLY LARVA (MUSCA-DOMESTICA)
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DOI：
10.1002/ps.2780390405
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发表时间：
1993-01-01
期刊：
影响因子：
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通讯作者：
OSBORNE, MP
中科院分区：
文献类型：
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作者：
PEPPER, DR;OSBORNE, MP
本文研究了拟除虫菊酯对家蝇幼虫（Musca domestica L.）敏感品系（Cooper）和抗击倒品系（kdr; super-kdr）离体节段神经和神经肌肉连接的影响。分离的节段性神经既没有细胞体，也没有突触接触；因此，拟除虫菊酯的任何作用都仅归因于它们对电压依赖性Na+通道的作用。测定了提高这些神经自发放电率所需的II型拟除虫菊酯（溴氰菊酯）的阈值浓度。两种抗性品系对溴氰菊酯的敏感性均比敏感品系低10倍左右，但对超kdr神经的不敏感程度不大于抗性较低的kdr品系。在神经肌肉连接处，对溴氰菊酯和I型拟除虫菊酯——氟氟菊酯，测定了触发微型兴奋性突触后电位（mesps）频率大量增加所需的最低浓度。在使用氟氰菊酯时，kdr和超级kdr菌株的连接之间没有可检测到的差异，它们的敏感性都比库珀连接低10倍左右。溴氰菊酯对kdr结的敏感性比Cooper低约30倍；super-kdr结对溴氰菊酯的敏感性比Cooper和kdr分别低10000倍和300倍。因此，在突触试验中，super-kdr仅对II型拟除虫菊酯类杀虫剂的抗性超过kdr，而对氟菊酯无效。我们认为kdr抗性包括神经系统中至少两个位点不敏感区域。一种与Na+通道不敏感有关，并且在kdr和超级kdr菌株中对i型和II型拟除虫菊酯具有相似的功效；另一个与突触前末端有关，对II型拟除虫菊酯的超级kdr抗性特别有效。后者可能与参与神经递质释放的Ca2+激活的蛋白质磷酸化有关。这种磷酸化反应已知会受到拟除虫菊酯的干扰，尤其是II型化合物。
The effects of pyrethroids were studied upon isolated segmental nerves and neuromuscular junctions in both susceptible (Cooper) and knockdown-resistant (kdr; super-kdr) strains of housefly larvae (Musca domestica L.). Isolated segmental nerves contained neither cell bodies nor synaptic contacts; thus, any effects of pyrethroids were attributed solely to their actions upon voltage-dependent Na+ channels. Threshold concentrations of the type II pyrethroid, deltamethrin, required to elevate the spontaneous firing rate of these nerves were determined. Both resistant strains were about ten times less sensitive to deltamethrin than the susceptible strain, but insensitivity of super-kdr nerves was no greater than in the less resistant kdr strain. At neuromuscular junctions, the minimum concentrations of pyrethroids needed to trigger massive increases in the frequency of miniature excitatory postsynaptic potentials (mEPSPs) were determined for deltamethrin and the type I pyrethroid, fenfluthrin. With fenfluthrin there was no detectable difference between the junctions of kdr and super-kdr strains, which were both about ten-fold less sensitive than Cooper junctions. With deltamethrin, kdr junctions were about 30 times less sensitive than those of Cooper; super-kdr junctions were dramatically insensitive to deltamethrin, being some 10000- and 300-fold less sensitive than those of Cooper and kdr respectively. Thus, in the synaptic assay, super-kdr conferred an extension in resistance over kdr only against the type II pyrethroid, it being ineffective against fenfluthrin. We suggest that kdr resistance comprises at least two site-insensitive areas within the nervous system. One involves insensitivity of the Na+ channel and has similar efficacy in both kdr and super-kdr strains against type -I and II pyrethroids; the other is associated with the presynaptic terminal and is particularly effective in super-kdr resistance against type II pyrethroids. The latter could be associated with Ca2+-activated phosphorylation of proteins involved with neurotransmitter release. Such phosphorylation reactions are known to be perturbed by pyrethroids, especially by type II compounds.