Insect olfactory receptors are heteromeric ligand-gated ion channels

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(1-9). 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(10-16). Insect ORs lack homology to G- protein-coupled chemosensory receptors in vertebrates(17) and possess a distinct seven- transmembrane topology with the amino terminus located intracellularly(10,18). Here we provide evidence that heteromeric insect ORs comprise a new class of ligand- activated nonselective 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.