Characterization in Potent Modulation on Voltage-Gated Na<sup>+</sup> Current Exerted by Deltamethrin, a Pyrethroid Insecticide
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 volta...
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MDPI AG
2022-11-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/23/14733 |
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| author | Mao-Hsun Lin Jen-Feng Lin Meng-Cheng Yu Sheng-Nan Wu Chao-Liang Wu Hsin-Yen Cho |
| author_facet | Mao-Hsun Lin Jen-Feng Lin Meng-Cheng Yu Sheng-Nan Wu Chao-Liang Wu Hsin-Yen Cho |
| author_sort | Mao-Hsun Lin |
| collection | DOAJ |
| description | 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<sup>+</sup> (Na<sub>V</sub>) channel current. In this study, we reappraised whether and how it and other related compounds can make any further modifications on voltage-gated Na<sup>+</sup> current (<i>I</i><sub>Na</sub>) in pituitary tumor (GH<sub>3</sub>) cells. Cell exposure to DLT produced a differential and dose-dependent stimulation of peak (transient, <i>I</i><sub>Na(T)</sub>) or sustained (late, <i>I</i><sub>Na(L)</sub>) <i>I</i><sub>Na</sub>; consequently, the EC<sub>50</sub> value required for DLT-stimulated <i>I</i><sub>Na(T)</sub> or <i>I</i><sub>Na(L)</sub> was determined to be 11.2 or 2.5 μM, respectively. However, neither the fast nor slow component in the inactivation time constant of <i>I</i><sub>Na(T)</sub> activated by short depolarizing pulse was changed with the DLT presence; conversely, tefluthrin (Tef), a type-I pyrethroid insecticide, can accentuate <i>I</i><sub>Na</sub> with a slowing in inactivation time course of the current. The <i>I</i><sub>Na(L)</sub> 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 <i>I</i><sub>Na(T)</sub> 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 <i>I</i><sub>Na(L)</sub> and tail <i>I</i><sub>Na</sub> (<i>I</i><sub>Na(Tail)</sub>) 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<sub>(V)</sub>) of persistent <i>I</i><sub>Na</sub> was differentially augmented by Tef or DLT. Taken together, the magnitude, gating, frequency dependence, as well as Hys<sub>(V)</sub> behavior of <i>I</i><sub>Na</sub> 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. |
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| spelling | doaj.art-2b60ccd52cfa4396bc0fcd4a03bf1bc72023-11-24T11:06:57ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-11-0123231473310.3390/ijms232314733Characterization in Potent Modulation on Voltage-Gated Na<sup>+</sup> Current Exerted by Deltamethrin, a Pyrethroid InsecticideMao-Hsun Lin0Jen-Feng Lin1Meng-Cheng Yu2Sheng-Nan Wu3Chao-Liang Wu4Hsin-Yen Cho5Division of Neurology, Department of Internal Medicine, Ditmanson Medical Foundation Chiayi Christian Hospital, Chiayi City 600, TaiwanDepartment of Emergency Medicine, Ditmanson Medical Foundation Chiayi Christian Hospital, Chiayi City 600, TaiwanDepartment of Physiology, National Cheng Kung University Medical College, Tainan 701, TaiwanDepartment of Physiology, National Cheng Kung University Medical College, Tainan 701, TaiwanDitmanson Medical Foundation Chiayi Christian Hospital, Chiayi City 600, TaiwanDepartment of Physiology, National Cheng Kung University Medical College, Tainan 701, TaiwanDeltamethrin (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<sup>+</sup> (Na<sub>V</sub>) channel current. In this study, we reappraised whether and how it and other related compounds can make any further modifications on voltage-gated Na<sup>+</sup> current (<i>I</i><sub>Na</sub>) in pituitary tumor (GH<sub>3</sub>) cells. Cell exposure to DLT produced a differential and dose-dependent stimulation of peak (transient, <i>I</i><sub>Na(T)</sub>) or sustained (late, <i>I</i><sub>Na(L)</sub>) <i>I</i><sub>Na</sub>; consequently, the EC<sub>50</sub> value required for DLT-stimulated <i>I</i><sub>Na(T)</sub> or <i>I</i><sub>Na(L)</sub> was determined to be 11.2 or 2.5 μM, respectively. However, neither the fast nor slow component in the inactivation time constant of <i>I</i><sub>Na(T)</sub> activated by short depolarizing pulse was changed with the DLT presence; conversely, tefluthrin (Tef), a type-I pyrethroid insecticide, can accentuate <i>I</i><sub>Na</sub> with a slowing in inactivation time course of the current. The <i>I</i><sub>Na(L)</sub> 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 <i>I</i><sub>Na(T)</sub> 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 <i>I</i><sub>Na(L)</sub> and tail <i>I</i><sub>Na</sub> (<i>I</i><sub>Na(Tail)</sub>) 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<sub>(V)</sub>) of persistent <i>I</i><sub>Na</sub> was differentially augmented by Tef or DLT. Taken together, the magnitude, gating, frequency dependence, as well as Hys<sub>(V)</sub> behavior of <i>I</i><sub>Na</sub> 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.https://www.mdpi.com/1422-0067/23/23/14733pyrethroidsvoltage-gated Na<sup>+</sup> currentlate Na<sup>+</sup> currenttransient Na<sup>+</sup> currentpersistent Na<sup>+</sup> current |
| spellingShingle | Mao-Hsun Lin Jen-Feng Lin Meng-Cheng Yu Sheng-Nan Wu Chao-Liang Wu Hsin-Yen Cho Characterization in Potent Modulation on Voltage-Gated Na<sup>+</sup> Current Exerted by Deltamethrin, a Pyrethroid Insecticide International Journal of Molecular Sciences pyrethroids voltage-gated Na<sup>+</sup> current late Na<sup>+</sup> current transient Na<sup>+</sup> current persistent Na<sup>+</sup> current |
| title | Characterization in Potent Modulation on Voltage-Gated Na<sup>+</sup> Current Exerted by Deltamethrin, a Pyrethroid Insecticide |
| title_full | Characterization in Potent Modulation on Voltage-Gated Na<sup>+</sup> Current Exerted by Deltamethrin, a Pyrethroid Insecticide |
| title_fullStr | Characterization in Potent Modulation on Voltage-Gated Na<sup>+</sup> Current Exerted by Deltamethrin, a Pyrethroid Insecticide |
| title_full_unstemmed | Characterization in Potent Modulation on Voltage-Gated Na<sup>+</sup> Current Exerted by Deltamethrin, a Pyrethroid Insecticide |
| title_short | Characterization in Potent Modulation on Voltage-Gated Na<sup>+</sup> Current Exerted by Deltamethrin, a Pyrethroid Insecticide |
| title_sort | characterization in potent modulation on voltage gated na sup sup current exerted by deltamethrin a pyrethroid insecticide |
| topic | pyrethroids voltage-gated Na<sup>+</sup> current late Na<sup>+</sup> current transient Na<sup>+</sup> current persistent Na<sup>+</sup> current |
| url | https://www.mdpi.com/1422-0067/23/23/14733 |
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