Root-knot nematodes are important plant parasitic nematodes, which cause serious damage to a wide range of crops. Fumigants and non-fumigants targeting acetylcholinesterase are currently used to control the nematodes. To examine whether γ-aminobutyric acid (GABA) receptors serve as a target of nematicides, we cloned an unc-49B orthologue from the southern root-knot nematode (Meloidogyne incognita) and investigated the ligand responses of homomeric UNC-49B channels expressed in Xenopus oocytes using a two-electrode voltage clamp technique. The extracellular orthosteric binding site and four transmembrane domains are conserved in M. incognita UNC-49B (Mi-UNC-49B), whereas a long second intracellular loop is characteristic of this protein. Mi-UNC-49B channels expressed in oocytes were less sensitive to GABA compared with other invertebrate GABA receptors. Picrotoxinin and fipronil inhibited GABA-induced currents in Mi-UNC-49B channels with micromolar and submicromolar IC50s, respectively. These channels became ~20-fold more sensitive to both picrotoxinin and fipronil by a mutation (G2’A) in the second transmembrane domain. A mutation (T6’M) in the same domain diminished the potency of picrotoxinin. Two nematicidal compounds, samaderine B and 4-cyclohexyl-3-isopropylbicyclophosphorothionate (SF-14), inhibited GABA-induced currents with micromolar and submicromolar IC50s, respectively. Essential oils (α-terpineol, thymol, and methyleugenol) and an anthelmintic macrolide alone (ivermectin) failed to activate Mi-UNC-49B channels. However, these compounds potentiated currents induced by low concentrations of GABA, whereas they antagonized currents induced by high concentrations of GABA. The unique pharmacology of Mi-UNC-49B channels should provide opportunities to develop specific nematicides.

Molecular pharmacology of homomeric UNC-49B channels from southern root-knot nematodes

250th National Meeting (2015)

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