Brunet L J, Gold G H, Ngai J
Department of Molecular and Cell Biology, University of California, Berkeley 94720, USA.
Neuron. 1996 Oct;17(4):681-93. doi: 10.1016/s0896-6273(00)80200-7.
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.
嗅觉神经元将气味分子的结合转化为膜去极化。两种细胞内信使，即环磷酸腺苷（cAMP）和肌醇三磷酸（IP3），被认为介导这一过程，cAMP对某些气味分子产生反应，而IP3介导对其他气味分子的反应。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。我们培育了一种缺乏功能性嗅觉CNG通道的突变“敲除”小鼠，以评估不同第二信使途径在嗅觉转导中的作用。使用电生理测定法，我们发现在敲除小鼠中，对产生cAMP和IP3的气味分子的兴奋性反应均无法检测到。我们的结果提供了直接证据，表明CNG通道参与兴奋性嗅觉信号转导，并且进一步表明cAMP是介导这一过程的唯一第二信使。
