A diacylglycerol-gated cation channel in vomeronasal neuron dendrites is impaired in TRPC2 mutant mice: mechanism of pheromone transduction.
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.
Lucas
Philippe
P
Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Ukhanov
Kyrill
K
Leinders-Zufall
Trese
T
Zufall
Frank
F
D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology; D044182:Benzylisoquinolines / Q000494:pharmacology; D001896:Boron Compounds / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000235:genetics / Q000502:physiology*; D003712:Dendrites / Q000187:drug effects* / Q000502:physiology; D019852:Diacylglycerol Kinase / Q000037:antagonists & inhibitors; D004075:Diglycerides / Q000032:analysis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004553:Electric Conductivity; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005071:Evoked Potentials / Q000187:drug effects; D005971:Glutamates / Q000494:pharmacology; D066298:In Vitro Techniques; D015544:Inositol 1,4,5-Trisphosphate / Q000494:pharmacology; D007473:Ion Channels; D008564:Membrane Potentials / Q000187:drug effects; D008565:Membrane Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D018408:Patch-Clamp Techniques; D010675:Pheromones / Q000378:metabolism*; D015398:Signal Transduction; D012964:Sodium / Q000378:metabolism; D050053:TRPM Cation Channels; D014556:Urine / Q000502:physiology; D019147:Vomeronasal Organ / Q000166:cytology* / Q000502:physiology
D000470:Alkaloids; D044182:Benzylisoquinolines; D001896:Boron Compounds; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D004075:Diglycerides; D004791:Enzyme Inhibitors; D005971:Glutamates; D007473:Ion Channels; D008565:Membrane Proteins; D010675:Pheromones; D050053:TRPM Cation Channels; C121934:TRPM2 protein, human; D016718:Arachidonic Acid; C009438:tetrandrine; C014574:gamma-glutamylmethylamide; D015544:Inositol 1,4,5-Trisphosphate; D012964:Sodium; C109986:2-aminoethoxydiphenyl borate; D019852:Diacylglycerol Kinase; D002118:Calcium