A diacylglycerol-gated cation channel in vomeronasal neuron dendrites is impaired in TRPC2 mutant mice: mechanism of pheromone transduction

Neuron. 2003 Oct 30;40(3):551-61. doi: 10.1016/s0896-6273(03)00675-5.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alkaloids / pharmacology
  • Animals
  • Arachidonic Acid / pharmacology
  • Benzylisoquinolines / pharmacology
  • Boron Compounds / pharmacology
  • Calcium / metabolism
  • Calcium Channel Blockers / pharmacology
  • Calcium Channels / genetics
  • Calcium Channels / physiology*
  • Dendrites / drug effects*
  • Dendrites / physiology
  • Diacylglycerol Kinase / antagonists & inhibitors
  • Diglycerides / analysis
  • Diglycerides / chemistry
  • Diglycerides / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Electric Conductivity
  • Electric Stimulation
  • Enzyme Inhibitors / pharmacology
  • Evoked Potentials / drug effects
  • Glutamates / pharmacology
  • In Vitro Techniques
  • Inositol 1,4,5-Trisphosphate / pharmacology
  • Ion Channels*
  • Membrane Potentials / drug effects
  • Membrane Proteins*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Neurons / drug effects*
  • Neurons / physiology
  • Patch-Clamp Techniques
  • Pheromones / metabolism*
  • Signal Transduction
  • Sodium / metabolism
  • TRPM Cation Channels
  • Urine / physiology
  • Vomeronasal Organ / cytology*
  • Vomeronasal Organ / physiology

Substances

  • Alkaloids
  • Benzylisoquinolines
  • Boron Compounds
  • Calcium Channel Blockers
  • Calcium Channels
  • Diglycerides
  • Enzyme Inhibitors
  • Glutamates
  • Ion Channels
  • Membrane Proteins
  • Pheromones
  • TRPM Cation Channels
  • TRPM2 protein, human
  • Arachidonic Acid
  • tetrandrine
  • gamma-glutamylmethylamide
  • Inositol 1,4,5-Trisphosphate
  • Sodium
  • 2-aminoethoxydiphenyl borate
  • Diacylglycerol Kinase
  • Calcium