Smith T J, Ingles P J, Soderlund D M
Department of Entomology, New York State Agricultural Experiment Station, Cornell University, Geneva 14456, USA.
Arch Insect Biochem Physiol. 1998;38(3):126-36. doi: 10.1002/(SICI)1520-6327(1998)38:3<126::AID-ARCH3>3.0.CO;2-Q.
Voltage-sensitive sodium channels encoded by the Vssc1 gene of the house fly (Musca domestica) were expressed in Xenopus laevis oocytes in combination with the tipE gene product of Drosophila melanogaster and were characterized by two-electrode voltage clamp. Vssc1/tipE sodium channels expressed in oocytes were highly sensitive to tetrodotoxin; half-maximal inhibition of sodium currents by tetrodotoxin was obtained at a concentration of 2.4 nM. Cismethrin, a pyrethroid that produces Type I effects on intact nerve, slowed the inactivation of sodium currents carried by Vssc1/tipE channels during a depolarizing pulse and induced a tail current after repolarization that decayed with a first-order time constant of approximately 650 ms. The voltage dependence of activation and steady-state inactivation of cismethrin-modified channels were shifted to more negative potentials. Cypermethrin, a pyrethroid with Type II effects on intact nerve, also prolonged the inactivation of Vssc1/tipE sodium channels and induced a tail current. However, the cypermethrin-induced tail current was extremely persistent, decaying with a first-order time constant of approximately 42 s. Unlike cismethrin, the effect of cypermethrin was use dependent, requiring repeated depolarizing pulses for the full development of modified sodium currents. The divergent effects of cismethrin and cypermethrin on Vssc1/tipE sodium channels expressed in oocytes are consistent with the actions of these and related compounds on sodium channels in invertebrate and vertebrate nerve preparations and provide insight into the mechanisms underlying the production of Type I and II effects on neuronal excitability.
家蝇（Musca domestica）Vssc1基因编码的电压敏感钠通道与果蝇（Drosophila melanogaster）的tipE基因产物一起在非洲爪蟾（Xenopus laevis）卵母细胞中表达，并通过双电极电压钳进行表征。卵母细胞中表达的Vssc1/tipE钠通道对河豚毒素高度敏感；河豚毒素对钠电流的半数最大抑制浓度为2.4 nM。顺式氯菊酯是一种对完整神经产生I型效应的拟除虫菊酯，在去极化脉冲期间减慢了Vssc1/tipE通道携带的钠电流的失活，并在复极化后诱导出一个尾电流，该尾电流以约650 ms的一级时间常数衰减。顺式氯菊酯修饰通道的激活和稳态失活的电压依赖性向更负的电位偏移。氯氰菊酯是一种对完整神经产生II型效应的拟除虫菊酯，也延长了Vssc1/tipE钠通道的失活并诱导出一个尾电流。然而，氯氰菊酯诱导的尾电流极其持久，以约42 s的一级时间常数衰减。与顺式氯菊酯不同，氯氰菊酯的作用具有使用依赖性，需要重复去极化脉冲才能使修饰的钠电流充分发展。顺式氯菊酯和氯氰菊酯对卵母细胞中表达的Vssc1/tipE钠通道的不同作用与这些及相关化合物对无脊椎动物和脊椎动物神经制剂中钠通道的作用一致，并为对神经元兴奋性产生I型和II型效应的潜在机制提供了见解。
