Citation

Münch J, Billig G, Huebner CA, Leinders-Zufall T, Zufall F, Jentsch TJ. J. Biol. Chem. 2018; 293(26): 10392-10403.

Affiliation

Physiology and Pathology of Ion Transport, Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP) and Max-Delbrück-Centrum für Molekulare Medizin, Germany.

Copyright

(Copyright © 2018, American Society for Biochemistry and Molecular Biology)

DOI

10.1074/jbc.RA118.003153

PMID

29769308

Abstract

Ca2+-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, Ca2+-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 Ca2+-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 Ca2+-activated Cl- currents. While these currents persisted in the VNOs of mice lacking Ano2, they were undetectable in olfactory neuron-specific Ano1 knock-out mice irrespective of the presence of Ano2. The loss of Ca2+-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 knock-out mice. We conclude that Ano1 mediates the bulk of Ca2+-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.

Published under license by The American Society for Biochemistry and Molecular Biology, Inc.

Language: en

Keywords

TMEM16A; TMEM16B; chloride channel; electrophysiology; neurobiology; patch clamp; signal transduction