1-stearoyl-2-arachidonoylglycerol and 2-aminoethoxydiphenyl-borate

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 Ca(2+)-permeable cation channel in vomeronasal neuron dendrites that is gated by the lipid messenger diacylglycerol (DAG), independently of Ca(2+) 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)P(3), Ca(2+) 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.

Topics: Alkaloids; Animals; Arachidonic Acid; Benzylisoquinolines; Boron Compounds; Calcium; Calcium Channel Blockers; Calcium Channels; Dendrites; Diacylglycerol Kinase; Diglycerides; Dose-Response Relationship, Drug; Drug Interactions; Electric Conductivity; Electric Stimulation; Enzyme Inhibitors; Evoked Potentials; Glutamates; In Vitro Techniques; Inositol 1,4,5-Trisphosphate; Ion Channels; Membrane Potentials; Membrane Proteins; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Neurons; Patch-Clamp Techniques; Pheromones; Signal Transduction; Sodium; TRPM Cation Channels; Urine; Vomeronasal Organ