| Title: | Ca(2+)-activated Cl(-) currents in the murine vomeronasal organ enhance neuronal spiking but are dispensable for male-male aggression |
| Author(s): | Munch J; Billig G; Hubner CA; Leinders-Zufall T; Zufall F; Jentsch TJ; |
| Address: | "From the Leibniz-Forschungsinstitut fur Molekulare Pharmakologie, D-13125 Berlin, Germany. the Max-Delbruck-Centrum fur Molekulare Medizin, D-13125 Berlin, Germany. the Graduate Program, Freie Universitat Berlin, D-14195 Berlin, Germany. Institut fur Humangenetik, Universitatsklinikum Jena, D-07747 Jena, Germany. the Center for Integrative Physiology and Molecular Medicine, Saarland University, D-66421 Homburg, Germany, and. From the Leibniz-Forschungsinstitut fur Molekulare Pharmakologie, D-13125 Berlin, Germany, Jentsch@fmp-berlin.de. the NeuroCure Cluster of Excellence, Charite Universitatsmedizin Berlin, D-10117 Berlin, Germany" |
| ISSN/ISBN: | 1083-351X (Electronic) 0021-9258 (Print) 0021-9258 (Linking) |
| Abstract: | "Ca(2+)-activated Cl(-) currents have been observed in many physiological processes, including sensory transduction in mammalian olfaction. The olfactory vomeronasal (or Jacobson's) organ (VNO) detects molecular cues originating from animals of the same species or from predators. It then triggers innate behaviors such as aggression, mating, or flight. In the VNO, Ca(2+)-activated Cl(-) channels (CaCCs) are thought to amplify the initial pheromone-evoked receptor potential by mediating a depolarizing Cl(-) efflux. Here, we confirmed the co-localization of the Ca(2+)-activated Cl(-) channels anoctamin 1 (Ano1, also called TMEM16A) and Ano2 (TMEM16B) in microvilli of apically and basally located vomeronasal sensory neurons (VSNs) and their absence in supporting cells of the VNO. Both channels were expressed as functional isoforms capable of giving rise to Ca(2+)-activated Cl(-) currents. Although these currents persisted in the VNOs of mice lacking Ano2, they were undetectable in olfactory neuron-specific Ano1 knockout mice irrespective of the presence of Ano2 The loss of Ca(2+)-activated Cl(-) currents resulted in diminished spontaneous and drastically reduced pheromone-evoked spiking of VSNs. Although this indicated an important role of anoctamin channels in VNO signal amplification, the lack of this amplification did not alter VNO-dependent male-male territorial aggression in olfactory Ano1/Ano2 double knockout mice. We conclude that Ano1 mediates the bulk of Ca(2+)-activated Cl(-) currents in the VNO and that Ano2 plays only a minor role. Furthermore, vomeronasal signal amplification by CaCCs appears to be dispensable for the detection of male-specific pheromones and for near-normal aggressive behavior in mice" |
| Keywords: | *Aggression Animals Anoctamin-1/metabolism Anoctamins/metabolism Chloride Channels/*metabolism *Electrophysiological Phenomena Gene Expression Regulation Male Mice Neurons/*cytology Vomeronasal Organ/cytology/metabolism/*physiology Tmem16a Tmem16b chlorid; |
| Notes: | "MedlineMunch, Jonas Billig, Gwendolyn Hubner, Christian A Leinders-Zufall, Trese Zufall, Frank Jentsch, Thomas J eng Research Support, Non-U.S. Gov't 2018/05/18 J Biol Chem. 2018 Jun 29; 293(26):10392-10403. doi: 10.1074/jbc.RA118.003153. Epub 2018 May 16" |
