Odorant inhibition of the olfactory cyclic nucleotide-gated channel with a native molecular assembly
Odorant inhibition of the olfactory cyclic nucleotide-gated channel with a native molecular assembly
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DOI：
10.1085/jgp.200609577
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发表时间：
2006-09-01
影响因子：
3.8
通讯作者：
Kurahashi, Takashi
中科院分区：
文献类型：
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作者：
Chen, Tsung-Yu;Takeuchi, Hiroko;Kurahashi, Takashi
人类嗅觉包括由气味分子触发的兴奋和抑制的相反作用。在嗅觉受体神经元中，气味分子不仅触发G蛋白偶联的信号级联，而且还产生各种机制来微调气味诱导的电流，包括嗅觉信号的低选择性气味抑制。这种大范围的嗅觉抑制被认为是在离子通道的水平上，但没有确切的证据。在这里，我们报告说，环核苷酸门控（CNG）阳离子通道，这是一个关键的元素，将气味刺激转化为电信号，被抑制结构无关的气味，与广泛的嗅觉抑制的表达一致。有趣的是，在仅由主通道亚基CNGA 2组成的同源寡聚CNG通道中抑制作用较小，但在由多种类型的亚基组成的通道中变得较大。然而，即使在含有所有天然亚基的通道中，对克隆的CNG通道的抑制的效力似乎小于先前在天然嗅觉神经元中所示的。尽管如此，我们的研究结果进一步表明，如果去除随后由Ca（2+）介导的分子步骤，天然神经元中的气味物质供应量很小。因此，目前的工作也表明，CNG通道开关的嗅觉信号通路，和开和关信号都可能被放大的后续嗅觉信号步骤。
Human olfaction comprises the opposing actions of excitation and inhibition triggered by odorant molecules. In olfactory receptor neurons, odorant molecules not only trigger a G-protein-coupled signaling cascade but also generate various mechanisms to fine tune the odorant-induced current, including a low-selective odorant inhibition of the olfactory signal. This wide-range olfactory inhibition has been suggested to be at the level of ion channels, but definitive evidence is not available. Here, we report that the cyclic nucleotide-gated ( CNG) cation channel, which is a key element that converts odorant stimuli into electrical signals, is inhibited by structurally unrelated odorants, consistent with the expression of wide-range olfactory inhibition. Interestingly, the inhibitory effect was small in the homo-oligomeric CNG channel composed only of the principal channel subunit, CNGA2, but became larger in channels consisting of multiple types of subunits. However, even in the channel containing all native subunits, the potency of the suppression on the cloned CNG channel appeared to be smaller than that previously shown in native olfactory neurons. Nonetheless, our results further showed that odorant suppressions are small in native neurons if the subsequent molecular steps mediated by Ca(2+) are removed. Thus, the present work also suggests that CNG channels switch on and off the olfactory signaling pathway, and that the on and off signals may both be amplified by the subsequent olfactory signaling steps.