TRP vanilloid 2 knock-out mice are susceptible to perinatal lethality but display normal thermal and mechanical nociception.
TRP vanilloid 2 knock-out mice are susceptible to perinatal lethality but display normal thermal and mechanical nociception.
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DOI：
10.1523/jneurosci.1384-09.2011
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发表时间：
2011-08-10
期刊：
影响因子：
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通讯作者：
Caterina MJ
中科院分区：
文献类型：
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作者：
Park U;Vastani N;Guan Y;Raja SN;Koltzenburg M;Caterina MJ
TRPV2是一种非选择性阳离子通道，在中至大直径感觉神经元中显著表达，可被极端高温（> - 52°C）激活。这些特征表明TRPV2可能是体内有害热量的传感器。TRPV2也可以被低渗或细胞拉伸激活，提示其在机械转导中的潜在作用。为了研究TRPV2在体感觉中的生理功能，我们制造了TRPV2基因敲除小鼠，并检测了它们对热刺激和机械刺激的行为和电生理反应。TRPV2基因敲除小鼠显示胚胎重量和围产期生存能力降低。成年后，幸存的基因敲除小鼠的体重也略有减轻。TRPV2基因敲除小鼠在基础状态和痛觉过敏（如外周炎症和L5脊髓神经结扎）条件下，对广泛温度范围内的有害热表现出正常的行为反应，对点状机械刺激表现出正常的反应。此外，对TRPV1/TRPV2双敲除小鼠或TRPV2敲除小鼠用树脂干扰素处理以脱敏TRPV1表达事件的行为分析显示，TRPV2缺失没有引起热感反应。与行为学发现一致，皮肤传入的电生理记录显示，在缺乏TRPV2的情况下，C-纤维对热的反应以及C-和a -纤维对有害机械刺激的反应没有受损。热敏a δ-纤维的流行率太低，无法进行基因型之间的比较。因此，TRPV2对围产期生存能力很重要，但对成年小鼠的热或机械性伤害感受或超敏反应不是必需的。
TRPV2 is a nonselective cation channel expressed prominently in medium- to large-diameter sensory neurons that can be activated by extreme heat (>52°C). These features suggest that TRPV2 might be a transducer of noxious heat in vivo. TRPV2 can also be activated by hypoosmolarity or cell stretch, suggesting potential roles in mechanotransduction. To address the physiological functions of TRPV2 in somatosensation, we generated TRPV2 knockout mice and examined their behavioral and electrophysiological responses to heat and mechanical stimuli. TRPV2 knockout mice showed reduced embryonic weight and perinatal viability. As adults, surviving knockout mice also exhibited a slightly reduced body weight. TRPV2 knockout mice showed normal behavioral responses to noxious heat over a broad range of temperatures and normal responses to punctate mechanical stimuli, both in the basal state and under hyperalgesic conditions such as peripheral inflammation and L5 spinal nerve ligation. Moreover, behavioral assays of TRPV1/TRPV2 double knockout mice or of TRPV2 knockout mice treated with resiniferatoxin to desensitize TRPV1-expressing afferents revealed no thermosensory consequences of TRPV2 absence. In line with behavioral findings, electrophysiological recordings from skin afferents showed that C-fiber responses to heat and C- and Aδ-fiber responses to noxious mechanical stimuli were unimpaired in the absence of TRPV2. The prevalence of thermosensitive Aδ-fibers was too low to permit comparison between genotypes. Thus, TRPV2 is important for perinatal viability but is not essential for heat or mechanical nociception or hypersensitivity in the adult mouse.