Indoxacarb, an oxadiazine insecticide, blocks insect neuronal sodium channels
Indoxacarb, an oxadiazine insecticide, blocks insect neuronal sodium channels
复制标题
DOI：
10.1038/sj.bjp.0703853
复制
发表时间：
2001-01-01
影响因子：
7.3
通讯作者：
Sattelle, DB
中科院分区：
文献类型：
--
作者：
Lapied, B;Grolleau, F;Sattelle, DB
新型噻嗪类杀虫剂DPX-JW062 （Indoxacarb）的活性成分decarbomethoxyylated JW062 （DCJW）。对短期培养的美洲大蠊背侧未配对正中神经元的动作电位和向内钠电流进行了测定在全细胞电流箝位条件下，100 nM DCJW降低了动作电位的幅度，诱导静息膜电位的大超极化，并导致输入电阻增加41%在电压箝位中，DCJW对钠离子峰值电流有剂量依赖性抑制（IC50为28 nM）。根据IC50值，DCJW的效力比河豚毒素（TTX）低约10倍，但比局麻利多卡因强1000倍。DCJW （100 nM）对钠电流的激活特性、逆转电位、钠电导的电压依赖性以及快速和慢速稳态失活均无影响TTX （2 nM）对钠离子向内电流峰值的抑制率为48%。TTX （2 nM）与不同浓度的DCJW一起作用，会对峰值内向电流产生额外的抑制，表明DCJW和TTX的阻断作用是不同的。不同浓度的DCJW与利多卡因（IC50 - 30mum）共同作用可使DCJW的表观效价降低，提示DCJW与利多卡因作用于同一部位DCJW （100 nM）不影响向内钙电流和向外钾电流本研究首次描述了一类新型杀虫剂茚虫威对昆虫神经元电压依赖性钠通道的作用。
1 Decarbomethoxyllated JW062 (DCJW), the active component of a new oxadiazine insecticide DPX-JW062 (Indoxacarb). was tested on action potentials and the inward sodium current recorded from short-term cultured dorsal unpaired median neurones of the cockroach Periplaneta americana.2 Under whole-cell current-clamp conditions, 100 nM DCJW reduced the amplitude of action potentials and induced a large hyperpolarization of the resting membrane potential associated with a 41% increase in input resistance.3 In voltage-clamp, DCJW resulted in a dose-dependent inhibition (IC50 28 nM) of the peak sodium current. Based on IC50 values, the effect of DCJW was about 10 fold less potent than tetrodotoxin (TTX) but 1000 fold more potent than the local anaesthetic lidocaine. DCJW (100 nM) was without effect on activation properties of the sodium current, reversal potential, voltage dependence of sodium conductance and on both fast and slow steady-state inactivations.4 TTX (2 nM) resulted in 48% inhibition of the peak inward sodium current. Go-application of TTX (2 nM) with various concentrations of DCJW produced an additional inhibition of the peak inward current, indicating that the blocking actions of DCJW and TTX were distinct. Coapplication of lidocaine (IC50 30 muM) with various concentrations of DCJW produced a reduction of the apparent potency of DCJW, suggesting that DCJW and lidocaine acted at the same site.5 DCJW (100 nM) did not affect inward calcium or outward potassium currents.6 This study describes, for the first time, the action on insect neuronal voltage-dependent sodium channels of Indoxacarb, a new class of insecticides.