SISSA, International School for Advanced Studies, and Italian Institute of Technology, SISSA Unit, Via Bonomea 265, 34136 Trieste, Italy.
Exp Physiol. 2012 Feb;97(2):193-9. doi: 10.1113/expphysiol.2011.058230. Epub 2011 Sep 2.
In vertebrate olfactory transduction, a Ca(2+)-dependent Cl(-) efflux greatly amplifies the odorant response. The binding of odorants to receptors in the cilia of olfactory sensory neurons activates a transduction cascade that involves the opening of cyclic nucleotide-gated channels and the entry of Ca(2+) into the cilia. The Ca(2+) activates a Cl(-) current that, in the presence of a maintained elevated intracellular Cl(-) concentration, produces an efflux of Cl(-) ions and amplifies the depolarization. In this review, we summarize evidence supporting the hypothesis that anoctamin 2/TMEM16B is the main, or perhaps the only, constituent of the Ca(2+)-activated Cl(-) channels involved in olfactory transduction. Indeed, studies from several laboratories have shown that anoctamin 2/TMEM16B is expressed in the ciliary layer of the olfactory epithelium, that there are remarkable functional similarities between currents in olfactory sensory neurons and in HEK 293 cells transfected with anoctamin 2/TMEM16B, and that knockout mice for anoctamin 2/TMEM16B did not show any detectable Ca(2+)-activated Cl(-) current. Finally, we discuss the involvement of Ca(2+)-activated Cl(-) channels in the transduction process of vomeronasal sensory neurons and the physiological role of these channels in olfaction.
在脊椎动物嗅觉转导中，钙离子依赖的氯离子外流极大地放大了气味反应。气味物质与嗅感觉神经元纤毛中的受体结合，激活了转导级联反应，包括环核苷酸门控通道的开放和钙离子进入纤毛。钙离子激活氯离子电流，在维持升高的细胞内氯离子浓度的情况下，产生氯离子的外流并放大去极化。在这篇综述中，我们总结了支持以下假设的证据：ANOCTAMIN 2/TMEM16B 是参与嗅觉转导的钙离子激活氯离子通道的主要（或者可能是唯一）组成部分。事实上，来自几个实验室的研究表明，ANOCTAMIN 2/TMEM16B 在嗅上皮的纤毛层中表达，嗅觉感觉神经元中的电流与用ANOCTAMIN 2/TMEM16B 转染的 HEK 293 细胞中的电流之间存在显著的功能相似性，ANOCTAMIN 2/TMEM16B 敲除小鼠没有显示出任何可检测到的钙离子激活氯离子电流。最后，我们讨论了钙离子激活氯离子通道在犁鼻感觉神经元转导过程中的参与以及这些通道在嗅觉中的生理作用。
