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

Area of Science:

• Electrophysiology
• Molecular Biology
• Insect Physiology

Background:

• Pacemaker channels (HCN) are crucial for electrical activity in excitable cells, including invertebrates.
• Understanding invertebrate HCN channels provides insights into fundamental biological processes and potential targets for environmental agents.

Purpose of the Study:

• To characterize the biophysical properties of the Apis mellifera (honeybee) HCN channel.
• To investigate the effects of the pesticide chlordecone on bee HCN channel function.

Main Methods:

• Heterologous expression of bee HCN in Xenopus oocytes and HEK cells.
• Electrophysiological recordings to assess channel activation, modulation, and block.
• Molecular docking using AlphaFold3 to predict pesticide binding sites.

Main Results:

• The bee HCN channel is activated by hyperpolarization, modulated by cAMP, and blocked by cesium, with a PNa/PK of 1:3 and 1.5 pS unitary conductance.
• Chlordecone inhibited Ih amplitude dose-dependently (IC50 = 9.37 µM) and reduced HCN conductance without altering voltage dependence.
• Molecular docking suggested chlordecone binds to the S6 helix region of the bee HCN channel.

Conclusions:

• The honeybee HCN channel exhibits functional similarities to mammalian HCN2.
• Chlordecone acts as a specific inhibitor of bee HCN channel conductance, potentially via binding to the S6 helix, offering insights into pesticide mechanisms.