Chlordecone reduces hyperpolarization-activated-current (Ih) conductance in honeybee

IF 4.2 3区环境科学与生态学 Q2 ENVIRONMENTAL SCIENCES Environmental toxicology and pharmacology Pub Date : 2025-03-01 Epub Date: 2025-02-19 DOI:10.1016/j.etap.2025.104659

Patrick Bois , Alain Chavanieu , Christophe Magaud , Nassim Fares , Mahira Kaabeche , Aurelien Chatelier , Pierre Charnet , Thierry Cens

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Abstract

The pacemaker channel (HCN) is responsible for electrical activity in a wide range of excitable cells, including those of invertebrates. Using Xenopus oocytes and HEK cell, we show here that HCN-channel from Apis mellifera is activated by hyperpolarization, modulated by cAMP, and blocked by cesium. Its PNa/PK relative permeability is 1:3, and its unitary conductance is 1.5 pS, which is similar to that of the mammalian HCN2 channel. Moreover, bee h-current is blocked by high concentrations of ZD7288, and organochlorine pesticide chlordecone reduces Ih amplitude in a dose-dependent manner (IC50 value was 9.37 µM) and diminishes HCN conductance, while preserving voltage dependence. In contrast, Deltamethrin exhibits no discernible impact. Molecular docking of Chlordecone in a homology model of bee HCN generated by AlphaFold3 suggests a binding site located at the end of the S6 helix that could explain the conductance inhibition caused by Chlordecone.

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十氯酮降低蜜蜂的超极化激活电流（Ih）电导

起搏器通道（HCN）负责包括无脊椎动物在内的多种可兴奋细胞的电活动。我们利用爪蟾卵母细胞和 HEK 细胞研究发现，蜂的 HCN 通道能被超极化激活，受 cAMP 调节，并被铯阻断。其 PNa/PK 相对通透性为 1:3，单位电导为 1.5 pS，与哺乳动物的 HCN2 通道相似。此外，蜜蜂的 h 电流会被高浓度的 ZD7288 阻断，有机氯杀虫剂十氯酮会以剂量依赖的方式降低 Ih 的振幅（IC50 值为 9.37 µM）并减弱 HCN 的传导，同时保持电压依赖性。相比之下，溴氰菊酯则没有明显的影响。十氯酮与 AlphaFold3 生成的蜜蜂 HCN 同源模型的分子对接表明，十氯酮的结合位点位于 S6 螺旋的末端，可以解释十氯酮对电导的抑制作用。

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来源期刊

Environmental toxicology and pharmacology 医学-毒理学

CiteScore

7.00

自引率

4.70%

发文量

185

审稿时长

34 days

期刊介绍： Environmental Toxicology and Pharmacology publishes the results of studies concerning toxic and pharmacological effects of (human and veterinary) drugs and of environmental contaminants in animals and man. Areas of special interest are: molecular mechanisms of toxicity, biotransformation and toxicokinetics (including toxicokinetic modelling), molecular, biochemical and physiological mechanisms explaining differences in sensitivity between species and individuals, the characterisation of pathophysiological models and mechanisms involved in the development of effects and the identification of biological markers that can be used to study exposure and effects in man and animals. In addition to full length papers, short communications, full-length reviews and mini-reviews, Environmental Toxicology and Pharmacology will publish in depth assessments of special problem areas. The latter publications may exceed the length of a full length paper three to fourfold. A basic requirement is that the assessments are made under the auspices of international groups of leading experts in the fields concerned. The information examined may either consist of data that were already published, or of new data that were obtained within the framework of collaborative research programmes. Provision is also made for the acceptance of minireviews on (classes of) compounds, toxicities or mechanisms, debating recent advances in rapidly developing fields that fall within the scope of the journal.