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 : 2025-02-19 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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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.