Characterization in Potent Modulation on Voltage-Gated Na + Current Exerted by Deltamethrin, a Pyrethroid Insecticide

• Published in: International journal of molecular sciences 2022-11, Vol.23 (23), p.14733
• Main Authors: Lin, Mao-Hsun, Lin, Jen-Feng, Yu, Meng-Cheng, Wu, Sheng-Nan, Wu, Chao-Liang, Cho, Hsin-Yen
• Format: Article
• Language: English
• Subjects: Amiloride; Brain tumors; Cell culture; Channel gating; Cyclopropanes; Deltamethrin; Depolarization; Frequency dependence; Hydrocarbons, Fluorinated; Insecticides; late Na+ current; persistent Na+ current; Pituitary; Poisoning; Public health; Pyrethrins - pharmacology; Pyrethroids; Recovery time; Sodium; Sodium channels (voltage-gated); Stimulation; Time constant; transient Na+ current; voltage-gated Na+ current
• ISSN: 1422-0067; 1661-6596; 1422-0067
• 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.