General anosmia caused by a targeted disruption of the mouse olfactory cyclic nucleotide-gated cation channel
General anosmia caused by a targeted disruption of the mouse olfactory cyclic nucleotide-gated cation channel
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DOI：
10.1016/s0896-6273(00)80200-7
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发表时间：
1996-10-01
期刊：
影响因子：
16.2
通讯作者：
Ngai, J
中科院分区：
文献类型：
--
作者：
Brunet, LJ;Gold, GH;Ngai, J
嗅觉神经元将气味的结合转化为膜去极化。两种细胞内信使，环AMP （cAMP）和肌醇三磷酸（IP3），被认为介导了这一过程，cAMP产生对某些气味的反应，IP3介导对其他气味的反应。cAMP通过激活阳离子选择性环核苷酸门控（CNG）通道引起膜去极化。我们创建了一个缺乏功能性嗅觉CNG通道的突变“敲除”小鼠，以评估不同的第二信使通路在嗅觉转导中的作用。通过电生理分析，我们发现在基因敲除小鼠中，对产生cAMP-和ip3的气味剂的兴奋性反应是检测不到的。我们的研究结果为CNG通道参与兴奋性嗅觉信号转导提供了直接证据，并进一步表明cAMP是介导这一过程的唯一第二信使。
Olfactory neurons transduce the binding of odorants into membrane depolarization. Two intracellular messengers, cyclic AMP (cAMP) and inositol trisphosphate (IP3), are thought to mediate this process, with cAMP generating responses to some odorants and IP3 mediating responses to others. cAMP causes membrane depolarization by activating a cation-selective cyclic nucleotide-gated (CNG) channel. We created a mutant ''knockout'' mouse lacking functional olfactory CNG channels to assess the roles of different second messenger pathways in olfactory transduction. Using an electrophysiological assay, we find that excitatory responses to both cAMP- and IP3-producing odorants are undetectable in knockout mice. Our results provide direct evidence that the CNG channel subserves excitatory olfactory signal transduction, and further suggest that cAMP is the sole second messenger mediating this process.