Vomeronasal sensory neurons play a crucial role in detecting pheromones, but the chemoelectrical transduction mechanism remains unclear and controversial. A major barrier to the resolution of this question has been the lack of an activation mechanism of a key transduction component, the TRPC2 channel. We have identified a Ca2+-permeable cation channel in vomeronasal neuron dendrites that is gated by the lipid messenger diacylglycerol (DAG), independently of Ca2+ or protein kinase C. We demonstrate that ablation of the TRPC2 gene causes a severe deficit in the DAG-gated channel, indicating that TRPC2 encodes a principal subunit of this channel and that the primary electrical response to pheromones depends on DAG but not Ins(1,4,5)P3, Ca2+ stores, or arachidonic acid. Thus, a previously unanticipated mechanism involving direct channel opening by DAG underlies the transduction of sensory cues in the accessory olfactory system.
