Three structurally similar odorants trigger distinct signaling pathways in a mouse olfactory neuron.

In the mammalian olfactory system, one olfactory sensory neuron (OSN) expresses a single olfactory receptor gene. By calcium imaging of individual OSNs in intact mouse olfactory turbinates, we observed that a subset of OSNs (Ho-OSNs) located in the most ventral olfactory receptor zone can mediate distinct signaling pathways when activated by structurally similar ligands. Calcium imaging showed that Ho-OSNs were highly sensitive to 2-heptanone, heptaldehyde and cis-4-heptenal. 2-heptanone-evoked intracellular calcium elevation was mediated by cAMP signaling while heptaldehyde triggered the diacylglycerol pathway. An increase of intracellular calcium evoked by cis-4-heptenal was due to a combination of activation mediated by the adenylate cyclase pathway and suppression generated by phospholipase C signaling. Pharmacological studies demonstrated that novel mechanisms were involved in the phospholipase C-mediated intracellular calcium changes. Binary-mixture studies and cross-adaptation data indicate that three odorants acted on the same olfactory receptor. The feature that an olfactory receptor mediates multiple signaling pathways was specific for Ho-OSNs and not established in another population of OSNs characterized. Our study suggests that distinct signaling pathways triggered by ligand-induced conformational changes of an olfactory receptor constitute a complex information process mechanism in olfactory transduction. This study has important implications beyond olfaction in that it provides insights of plasticity and complexity of G-protein-coupled receptor activation and signal transduction.