TRPV2 is required for mechanical nociception and the stretch-evoked response of primary sensory neurons.

TRPV2 is required for mechanical nociception and the stretch-evoked response of primary sensory neurons.
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DOI:
10.1038/s41598-018-35049-4
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发表时间:
2018-11-14
期刊:
影响因子:
4.6
通讯作者:
Katanosaka Y
Katanosaka Y
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Katanosaka K;Takatsu S;Mizumura K;Naruse K;Katanosaka Y

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机械转导在许多感觉过程中起着重要的作用,包括触摸、疼痛、听觉和本体感觉。然而,机械性伤害性感受的分子机制仍不清楚。在这里,我们发现小鼠瞬时受体电位香草素2(TRPV2)的消除导致机械伤害感觉的缺陷,这是由于成人初级感觉神经元(PSN)的一种亚类缺乏机械敏感性。PSN特异性TRPV2基因缺陷小鼠在尾压和von Frey毛发测试中显示出机械伤害性行为障碍,但在轴突生长和神经元组成方面没有缺陷。相反,小鼠对有害的高温和非有害的触觉刺激表现出正常的行为。此外,基于对培养的PSN的拉伸诱发的钙离子反应,我们在正常小鼠中表征了两种拉伸激活的神经元:快衰变的高阈值和慢衰的低阈值机械敏感性。培养的TRPV2基因缺陷小鼠的神经元缺乏由高阈值机械刺激激活的快速衰退神经元所产生的拉伸诱发的钙反应。这些结果表明,在成人躯体感觉系统中,TRPV2在机械伤害性感受中起着关键作用。
Mechanotransduction plays important roles in many sensory processes, including touch, pain, hearing, and proprioception. However, the molecular mechanisms of mechanical nociception have remained unclear. Here, we showed that elimination of transient receptor potential vanilloid 2 (TRPV2) in mice resulted in the deficit of mechanical nociception due to the lack of mechanosensitivity in a subclass of adult primary sensory neurons (PSNs). The PSN-specific TRPV2-deficient mice showed behavioural impairment of mechanical nociception in tail-pressure and von Frey hair tests, without defects in axonal growth and neuronal composition. Conversely, the mice displayed normal behaviour to noxious heat and non-noxious tactile stimuli. Furthermore, based on the stretch-evoked Ca2+ response of cultured PSNs, we characterised two types of stretch-activated neurons in normal mice; fast-decay high-threshold and slow-decay low-threshold mechanosensitive. The cultured neurons from TRPV2-deficient mice lacked stretch-evoked Ca2+ responses by fast-decay neurons normally activated by high-threshold mechanical stimulation. These results demonstrated that TRPV2 has a critical role in mechanical nociception in the adult somatosensory system.
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