Ivermectin modulation of pH-sensitive chloride channels in the silkworm larvae of Bombyx mori

Abstract

The pH-sensitive chloride channels (pHCls) are expressed widely in the insect nervous system, but their physiological roles and pesticide sensitivity in Lepidoptera are poorly understood. Here, cDNAs of pHCl variants “A” and “B” were isolated from the head of silkworm (Bombyx mori) larvae and expressed in Xenopus laevis oocytes to characterize their functions and examine their pesticide sensitivity. Variant “A” possesses four entire transmembrane domains (TMs), while variant “B” lacks a part of the TM and the TM3–TM4 linker. Only the A variant formed a chloride channel in oocytes which was activated in response to an increase of pH in the extracellular solution. Neither fipronil nor γ-benzenehexachloride had a significant blocking effect on the A variant when tested at 10μM. By contrast, macrolide ivermectin activated it at acidic pH but blocked it at pH7.6 at concentrations higher than 300nM, indicating a likely contribution to in vivo toxicity.