Ca2+-activated Cl− currents in the murine vomeronasal organ enhance neuronal spiking but are dispensable for male–male aggression
Ca2+-activated Cl− currents in the murine vomeronasal organ enhance neuronal spiking but are dispensable for male–male aggression
复制标题
DOI：
10.1074/jbc.ra118.003153
复制
发表时间：
2018-05
期刊：
影响因子：
--
通讯作者：
Jonas Münch;Gwendolyn Billig;C. Hübner;Trese Leinders-Zufall;F. Zufall;T. Jentsch
中科院分区：
文献类型：
--
作者：
Jonas Münch;Gwendolyn Billig;C. Hübner;Trese Leinders-Zufall;F. Zufall;T. Jentsch
Ca2+激活的Cl -电流在许多生理过程中被观察到，包括哺乳动物嗅觉的感觉转导。嗅觉犁鼻（或雅各布森）器官（VNO）检测来自同一物种动物或掠食者的分子线索。然后，它会引发与生俱来的行为，比如攻击、交配或逃跑。在VNO中，Ca2+激活的Cl -通道（CaCCs）被认为通过介导去极化Cl -外排来放大初始信息素诱发的受体电位。在这里，我们证实了Ca2+激活的Cl -通道anoctamin 1 （Ano1，也称为TMEM16A）和Ano2 （TMEM16B）在顶部和基部的vomeronasal感觉神经元（VSNs）的微绒毛中共定位，而它们在VNO的支持细胞中缺失。这两个通道都被表达为能够产生Ca2+激活的Cl -电流的功能亚型。尽管这些电流在缺乏Ano2的小鼠的VNOs中持续存在，但在嗅觉神经元特异性Ano1敲除小鼠中，无论是否存在Ano2，它们都无法检测到。Ca2+激活的Cl -电流的缺失导致VSNs自发峰的减少和信息素诱发的急剧减少。虽然这表明Ano1/Ano2双敲除嗅觉小鼠中Ano1/Ano2通道在VNO信号放大中起重要作用，但缺乏这种放大并没有改变VNO依赖的雄性-雄性领土攻击。我们得出结论，Ano1介导了VNO中大部分Ca2+激活的Cl -电流，而Ano2仅起次要作用。此外，CaCCs的犁鼻信号放大对于检测雄性特异性信息素和小鼠接近正常的攻击行为似乎是必不可少的。
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. 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 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 knockout 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.