TRPV3 and TRPV4 ion channels are not major contributors to mouse heat sensation.

TRPV3 and TRPV4 ion channels are not major contributors to mouse heat sensation.
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DOI:
10.1186/1744-8069-7-37
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发表时间:
2011-05-17
期刊:
影响因子:
3.3
通讯作者:
Caterina MJ
Caterina MJ
中科院分区:
医学3区
文献类型:
--
作者:
Huang SM;Li X;Yu Y;Wang J;Caterina MJ

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热敏瞬时受体电位香草蛋白(TRPV)离子通道的发现为无害和有害热刺激的感知提供了潜在的分子解释。TRPV1在急性热痛觉和炎症性热痛觉过敏中具有重要作用。然而,在TRPV1敲除的动物中,仍然存在大量的无害和有害的热敏性。在这里,我们研究了两个相关通道TRPV3和TRPV4在这些能力中的作用。我们研究了C57BL6和129S6背景下TRPV3基因敲除的动物,以及C57BL6背景下TRPV3和TRPV4基因缺失的动物。此外,我们评估了TRPV3和TRPV4在抑制TRPV1期间对急性热伤害和炎症性热痛觉过敏的贡献。C57BL6背景下TRPV3基因敲除小鼠的热偏好行为没有明显改变。在129S6背景下,TRPV3的缺失导致以较低的地板温度为中心的占用范围更有限。TRPV3基因敲除小鼠在两种背景下均未表现出急性热痛觉缺陷。C57BL6背景下TRPV3和TRPV4均缺失的小鼠在热梯度上表现出与野生型对照组相似的热偏好行为,急性热痛觉或炎症性热痛觉几乎没有变化。TRPV1拮抗剂JNJ-17203212在TRPV3和TRPV4缺乏的C57BL6动物与野生型动物相比,没有发现TRPV1的掩蔽作用。我们的研究结果支持TRPV3和TRPV4可能对无害的温暖温度感知或有害的热感觉做出有限的和菌株依赖的贡献的观点,即使TRPV1被掩盖。这些发现暗示存在其他重要的热感知机制。
The discovery of heat-sensitive Transient Receptor Potential Vanilloid (TRPV) ion channels provided a potential molecular explanation for the perception of innocuous and noxious heat stimuli. TRPV1 has a significant role in acute heat nociception and inflammatory heat hyperalgesia. Yet, substantial innocuous and noxious heat sensitivity remains in TRPV1 knockout animals. Here we investigated the role of two related channels, TRPV3 and TRPV4, in these capacities. We studied TRPV3 knockout animals on both C57BL6 and 129S6 backgrounds, as well as animals deficient in both TRPV3 and TRPV4 on a C57BL6 background. Additionally, we assessed the contributions of TRPV3 and TRPV4 to acute heat nociception and inflammatory heat hyperalgesia during inhibition of TRPV1. TRPV3 knockout mice on the C57BL6 background exhibited no obvious alterations in thermal preference behavior. On the 129S6 background, absence of TRPV3 resulted in a more restrictive range of occupancy centered around cooler floor temperatures. TRPV3 knockout mice showed no deficits in acute heat nociception on either background. Mice deficient in both TRPV3 and TRPV4 on a C57BL6 background showed thermal preference behavior similar to wild-type controls on the thermal gradient, and little or no change in acute heat nociception or inflammatory heat hyperalgesia. Masking of TRPV1 by the TRPV1 antagonist JNJ-17203212 did not reveal differences between C57BL6 animals deficient in TRPV3 and TRPV4, compared to their wild-type counterparts. Our results support the notion that TRPV3 and TRPV4 likely make limited and strain-dependent contributions to innocuous warm temperature perception or noxious heat sensation, even when TRPV1 is masked. These findings imply the existence of other significant mechanisms for heat perception.
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发表时间: 2003-06-20
影响因子: 4.8
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影响因子: 4.8
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期刊: Pflugers Archiv : European journal of physiology
影响因子: --
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