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      Insect olfactory receptors are heteromeric ligand-gated ion channels.

      Nature

      Xenopus laevis, Animals, Smell, metabolism, chemistry, Receptors, Odorant, Protein Subunits, Patch-Clamp Techniques, Oocytes, analysis, Odors, Ligands, Kinetics, Ion Channel Gating, Insects, Humans, Heterotrimeric GTP-Binding Proteins, HeLa Cells, Electric Conductivity, Drosophila melanogaster, Culicidae, Cell Line, Calcium, Bombyx

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          Abstract

          In insects, each olfactory sensory neuron expresses between one and three ligand-binding members of the olfactory receptor (OR) gene family, along with the highly conserved and broadly expressed Or83b co-receptor. The functional insect OR consists of a heteromeric complex of unknown stoichiometry but comprising at least one variable odorant-binding subunit and one constant Or83b family subunit. Insect ORs lack homology to G-protein-coupled chemosensory receptors in vertebrates and possess a distinct seven-transmembrane topology with the amino terminus located intracellularly. Here we provide evidence that heteromeric insect ORs comprise a new class of ligand-activated non-selective cation channels. Heterologous cells expressing silkmoth, fruitfly or mosquito heteromeric OR complexes showed extracellular Ca2+ influx and cation-non-selective ion conductance on stimulation with odorant. Odour-evoked OR currents are independent of known G-protein-coupled second messenger pathways. The fast response kinetics and OR-subunit-dependent K+ ion selectivity of the insect OR complex support the hypothesis that the complex between OR and Or83b itself confers channel activity. Direct evidence for odorant-gated channels was obtained by outside-out patch-clamp recording of Xenopus oocyte and HEK293T cell membranes expressing insect OR complexes. The ligand-gated ion channel formed by an insect OR complex seems to be the basis for a unique strategy that insects have acquired to respond to the olfactory environment.

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          Journal
          10.1038/nature06850
          18408712

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