TRPA1 channels mediate cold temperature sensing in mammalian vagal sensory neurons: Pharmacological and genetic evidence
TRPA1 channels mediate cold temperature sensing in mammalian vagal sensory neurons: Pharmacological and genetic evidence
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DOI：
10.1523/jneurosci.1696-08.2008
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发表时间：
2008-07-30
影响因子：
5.3
通讯作者：
Viana, Felix
中科院分区：
文献类型：
--
作者：
Fajardo, Otto;Meseguer, Victor;Viana, Felix
冷热感受器存在于迷走神经的不同区域。将冷温度应用于这些内脏传入可以引起主要的保护性反射和体温调节反应。然而，对迷走神经传入冷敏的传导机制几乎一无所知。在这里，我们研究了冷刺激对培养的大鼠结状神经节迷走感觉神经元细胞内钙反应和兴奋性的影响。很大一部分迷走神经被冷激活，平均阈值接近24摄氏度。冷伴随着小内向电流的形成和动作电位的激发。大多数冷敏感神经元也被热和辣椒素激活，这表明了伤害性功能。对TRPM8和TRPA1激动剂和拮抗剂的药理反应表明，与在躯体组织中观察到的结果不同，TRPA1是迷走神经内脏神经元冷诱发反应的主要介导物。因此，大多数冷诱发反应可被肉桂醛、薄荷脑、尼可林和BCTC[4-(3-chloro-pyridin-2-yl)-piperazine-1-carboxylic酸(4-叔丁基苯基)-酰胺增强，而被Ru红、樟脑和HC03001[2-(1，3-dimethyl-2，6-dioxo-1，2，3，6-tetrahydro-7H-purin-7-yl)-N-(4-异丙基苯乙酰胺抑制]。在小鼠的结状神经元中，结果显示了类似的冷诱发反应的药理学特征。此外，对TRPA1基因敲除小鼠的实验表明，与野生型动物相比，冷敏感神经元的百分比大幅下降。综上所述，这些结果支持TRPA1通道在内脏温度感受中的重要作用，并表明躯体和内脏感觉神经元之间在温度信号转导方面的重大差异。
Cold thermoreceptors have been described in different territories of the vagus nerve. Application of cold temperature to these visceral afferents can evoke major protective reflexes and thermoregulatory responses. However, virtually nothing is known about the transduction mechanisms underlying cold sensitivity in vagal afferents. Here, we investigated the effects of cold stimulation on intracellular calcium responses and excitability of cultured vagal sensory neurons in the rat nodose ganglion. A large fraction of vagal neurons were activated by cold, with a mean threshold of similar to 24 degrees C. Cooling was accompanied by development of a small inward current and the firing of action potentials. Most cold-sensitive neurons were also activated by heat and capsaicin, suggesting a nociceptive function. The pharmacological response to TRPM8 and TRPA1 agonists and antagonists suggested that, unlike results observed in somatic tissues, TRPA1 is the major mediator of cold-evoked responses in vagal visceral neurons. Thus, most cold-evoked responses were potentiated by cinnamaldehyde, menthol, icilin, and BCTC [4-(3-chloro-pyridin-2-yl)-piperazine-1-carboxylic acid (4-tert-butyl-phenyl)-amide], agonists of TRPA1, and were inhibited by ruthenium red, camphor, and HC03001 [2-(1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-7H-purin-7-yl)-N-(4- isopropylphenyl) acetamide]. Results in mouse nodose neurons revealed a similar pharmacological profile of cold-evoked responses. Furthermore, experiments in TRPA1 knock-out mice showed a large reduction in the percentage of cold-sensitive neurons compared with wild-type animals. Together, these results support an important role of TRPA1 channels in visceral thermosensation and indicate major differences in the transduction of temperature signals between somatic and visceral sensory neurons.