Division of Neurology, Department of Internal Medicine, Ditmanson Medical Foundation Chiayi Christian Hospital, Chiayi City 600, Taiwan.
Department of Emergency Medicine, Ditmanson Medical Foundation Chiayi Christian Hospital, Chiayi City 600, Taiwan.
Int J Mol Sci. 2022 Nov 25;23(23):14733. doi: 10.3390/ijms232314733.
Deltamethrin (DLT) is a type-II pyrethroid ester insecticide used in agricultural and domestic applications as well as in public health. However, transmembrane ionic channels perturbed by this compound remain largely unclear, although the agent is thought to alter the gating characteristics of voltage-gated Na (Na) channel current. In this study, we reappraised whether and how it and other related compounds can make any further modifications on voltage-gated Na current () in pituitary tumor (GH) cells. Cell exposure to DLT produced a differential and dose-dependent stimulation of peak (transient, ) or sustained (late, ) ; consequently, the EC value required for DLT-stimulated or was determined to be 11.2 or 2.5 μM, respectively. However, neither the fast nor slow component in the inactivation time constant of activated by short depolarizing pulse was changed with the DLT presence; conversely, tefluthrin (Tef), a type-I pyrethroid insecticide, can accentuate with a slowing in inactivation time course of the current. The augmented by DLT was attenuated by further application of either dapagliflozin (Dapa) or amiloride, but not by chlorotoxin. During pulse train (PT) stimulation, with the Tef or DLT presence, the cumulative inhibition of became slowed; moreover, following PT stimuli, a large tail current with a slowly recovering process was observed. Alternatively, during rapid depolarizing pulse, the amplitude of and tail () for each depolarizing pulse became progressively increased by adding DLT, not by Tef. The recovery time constant following PT stimulation with continued presence of Tef or DLT was shortened by further addition of Dapa. The voltage-dependent hysteresis (Hys) of persistent was differentially augmented by Tef or DLT. Taken together, the magnitude, gating, frequency dependence, as well as Hys behavior of exerted by the presence of DLT or Tef might exert a synergistic impact on varying functional activities of excitable cells in culture or in vivo.
溴氰菊酯（DLT）是一种 II 型拟除虫菊酯酯类杀虫剂，广泛应用于农业、家庭和公共卫生领域。然而，目前对于该化合物如何改变跨膜离子通道仍知之甚少，尽管该化合物被认为会改变电压门控钠（Na）通道电流的门控特性。在这项研究中，我们重新评估了 DLT 及其它相关化合物是否以及如何进一步改变垂体瘤（GH）细胞中的电压门控 Na 电流（）。细胞暴露于 DLT 后，会产生浓度依赖性的峰值（瞬态，）或持续（晚期，）刺激；因此，确定 DLT 刺激或的 EC 值分别为 11.2 或 2.5 μM。然而，无论在短去极化脉冲激活的失活时间常数中，快或慢成分都没有发生变化；相反，拟除虫菊酯杀虫剂氟氯氰菊酯（Tef）可以通过减慢电流失活时间进程来增强。用 DLT 增强的被随后加入的达格列净（Dapa）或阿米洛利所抑制，但氯毒素则没有。在脉冲串（PT）刺激期间，当存在 Tef 或 DLT 时，对的累积抑制作用会减缓；此外，在 PT 刺激后，观察到一个具有缓慢恢复过程的大尾电流。或者，在快速去极化脉冲期间，通过加入 DLT，而不是 Tef，每个去极化脉冲的的幅度和尾电流（）逐渐增加。在继续存在 Tef 或 DLT 的情况下，PT 刺激后的恢复时间常数通过进一步加入 Dapa 而缩短。PT 刺激后，持续存在 Tef 或 DLT 会使持续的的电压依赖性滞后（Hys）产生差异增强。综上所述，DLT 或 Tef 的存在会对培养或体内可兴奋细胞的功能活动产生协同影响，包括幅度、门控、频率依赖性以及 Hys 行为。
