Inhibitory Odorant Signaling in Mammalian Olfactory Receptor Neurons
Inhibitory Odorant Signaling in Mammalian Olfactory Receptor Neurons
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DOI：
10.1152/jn.00980.2009
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发表时间：
2010-02-01
影响因子：
2.5
通讯作者：
Ache, Barry W.
中科院分区：
文献类型：
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作者：
Ukhanov, Kirill;Corey, Elizabeth A.;Ache, Barry W.
Ukhanov K，Corey EA，Brunert D，Klasen K，Ache BW.哺乳动物嗅觉受体神经元中气味信号的抑制。神经生理学杂志103：1114-1122，2010年。首次发表于2009年12月23日; doi：10.1152/jn.00980.2009。气味剂抑制以及兴奋嗅觉受体神经元（ORN）在许多物种的动物。典型的哺乳动物ORN的环核苷酸依赖性激活已经很好地建立，但仍然不清楚气味剂如何抑制这些细胞。在这里，我们进一步牵连磷脂酰肌醇-3-激酶（PI 3 K），PI信号在许多细胞过程中不可或缺的元素，在啮齿类动物的嗅觉转导的ORN。我们发现，气味迅速和短暂激活PI 3 K的嗅觉纤毛和嗅觉上皮细胞在体外。我们牵连已知的G-蛋白偶联的PI 3 K亚型，并表明，他们不仅调制的幅度，但也发病动力学的电生理反应的ORN复杂的气味。最后，我们表明，一个单一的气味抑制另一个的能力可以是PI 3 K依赖的。我们的集体研究结果提供了令人信服的支持的想法，PI 3 K依赖性信号介导的抑制性气味输入哺乳动物ORN和至少部分有助于混合物抑制通常看到的ORN复杂的天然气味的反应。
Ukhanov K, Corey EA, Brunert D, Klasen K, Ache BW. Inhibitory odorant signaling in mammalian olfactory receptor neurons. J Neurophysiol 103: 1114-1122, 2010. First published December 23, 2009; doi:10.1152/jn.00980.2009. Odorants inhibit as well as excite olfactory receptor neurons (ORNs) in many species of animals. Cyclic nucleotide-dependent activation of canonical mammalian ORNs is well established but it is still unclear how odorants inhibit these cells. Here we further implicate phosphoinositide-3-kinase (PI3K), an indispensable element of PI signaling in many cellular processes, in olfactory transduction in rodent ORNs. We show that odorants rapidly and transiently activate PI3K in the olfactory cilia and in the olfactory epithelium in vitro. We implicate known G-protein-coupled isoforms of PI3K and show that they modulate not only the magnitude but also the onset kinetics of the electrophysiological response of ORNs to complex odorants. Finally, we show that the ability of a single odorant to inhibit another can be PI3K dependent. Our collective results provide compelling support for the idea that PI3K-dependent signaling mediates inhibitory odorant input to mammalian ORNs and at least in part contributes to the mixture suppression typically seen in the response of ORNs to complex natural odorants.