Identification of Cardiac Expression Pattern of Transient Receptor Potential Vanilloid Type 1 (TRPV1) Receptor using a Transgenic Reporter Mouse Model.
Identification of Cardiac Expression Pattern of Transient Receptor Potential Vanilloid Type 1 (TRPV1) Receptor using a Transgenic Reporter Mouse Model.
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DOI：
10.1016/j.neulet.2020.135320
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发表时间：
2020-10-15
影响因子：
2.5
通讯作者：
Wang HJ
中科院分区：
文献类型：
--
作者：
Hong J;Lisco AM;Rudebush TL;Yu L;Gao L;Kitzerow O;Zucker IH;Wang HJ
瞬时受体电位香草酸亚型1（TRPV1）通道属于结构相关的非选择性阳离子通道，对钙离子具有高通透性。表达TRPV1通道的感觉神经末梢在调节心脏交感传入反射中发挥着重要作用，并与慢性心力衰竭中的心脏重塑和功能障碍有关。然而，TRPV1通道在心肌细胞与非心肌细胞中的具体表达情况仍存在争议。在此，我们利用tdTomato - GFP报告基因小鼠与在TRPV1启动子控制下表达Cre重组酶的小鼠品系进行杂交，以绘制心脏中TRPV1的表达模式。在该模型中，TRPV1阴性细胞表达tdTomato蛋白（红色），而TRPV1阳性细胞表达GFP蛋白（绿色）。正如我们所预期的，在杂合的TRPV1 - Cre +/−、tdTomato flox/flox +/−雄性小鼠中，许多中小直径的背根神经节神经元中发现了大量的GFP表达，这表明这种杂合模型足以标记TRPV1阳性细胞。此外，这些结果显示在心肌细胞中检测不到GFP绿色染色。相反，我们在心脏的血管（推测为小动脉）中发现了强烈的GFP绿色染色。我们还在心外膜中PGP9.5阳性的心脏神经末梢上观察到强烈的GFP信号。总之，本研究不支持TRPV1通道在小鼠心肌细胞中大量表达这一观点。我们得出结论，小鼠心脏中的TRPV1通道主要表达于非心肌细胞，包括心脏神经末梢和血管。这些数据对心源性反射的调节具有重要意义。
Transient receptor potential vanilloid type 1 (TRPV1) channels are structurally related, nonselective cation channels that exhibit a high permeability to calcium. Sensory nerve endings expressing TRPV1 channels play a prominent role in regulating the cardiac sympathetic afferent reflex and contribute to cardiac remodeling and dysfunction in chronic heart failure. However, the precise expression of TRPV1 channels in cardiomyocytes vs. non-cardiomyocytes remains debated. Here we utilized a tdTomato-GFP reporter mouse crossed with a mouse line expressing Cre recombinase under the control of the TRPV1 promoter to map the TRPV1 expression pattern in heart. In this model, TRPV1-negative cells express tdTomato protein (red), whereas TRPV1-positive cells express GFP protein (green). As we expected, substantial GFP expression was found in many small and medium diameter dorsal root ganglia neurons in heterozygous TRPV1-Cre +/−, tdTomato flox/flox +/− male mice, suggesting that this heterozygous model is sufficient for labeling TRPV1-positive cells. Furthermore, these results showed that GFP green staining was not detectable in cardiomyocytes. Instead, we found strong GFP green staining in cardiac blood vessels—thought to be arterioles—in the heart. We also observed strong GFP signals on PGP9.5-positive cardiac nerve endings in the epicardium. In summary, this study does not support the concept that TRPV1 channels are strongly expressed in mouse cardiomyocytes. We conclude that TRPV1 channels in mouse heart are mostly expressed on non-cardiomyocyte cells including cardiac nerve endings and vessels. These data have important implications for the modulations of cardiogenic reflexes.
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DOI：
10.1523/jneurosci.6451-10.2011
发表时间：
2011-03-30
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Cavanaugh DJ;Chesler AT;Jackson AC;Sigal YM;Yamanaka H;Grant R;O'Donnell D;Nicoll RA;Shah NM;Julius D;Basbaum AI
通讯作者：
Basbaum AI
DOI：
10.1152/ajpregu.1996.271.3.r751
发表时间：
1996-09-01
影响因子：
2.8
作者：
Wang, W;Zucker, IH
通讯作者：
Zucker, IH
DOI：
10.1080/19336950.2016.1185579
发表时间：
2016-09-02
期刊：
Channels (Austin, Tex.)
影响因子：
--
作者：
Andrei SR;Sinharoy P;Bratz IN;Damron DS
通讯作者：
Damron DS
影响因子：
4.5
作者：
Brady, CM;Apostolidis, AN;Anand, P
通讯作者：
Anand, P
心脏交感神经传入的神经支配可减轻心脏衰竭大鼠的心血管重塑并改善心血管功能障碍。
DOI：
10.1161/hypertensionaha.114.03699
发表时间：
2014-10
期刊：
Hypertension (Dallas, Tex. : 1979)
影响因子：
--
作者：
Wang HJ;Wang W;Cornish KG;Rozanski GJ;Zucker IH
通讯作者：
Zucker IH