TRPA1 is functionally co-expressed with TRPV1 in cardiac muscle: Co-localization at z-discs, costameres and intercalated discs.
TRPA1 is functionally co-expressed with TRPV1 in cardiac muscle: Co-localization at z-discs, costameres and intercalated discs.
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DOI：
10.1080/19336950.2016.1185579
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发表时间：
2016-09-02
期刊：
影响因子：
--
通讯作者：
Damron DS
中科院分区：
文献类型：
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作者：
Andrei SR;Sinharoy P;Bratz IN;Damron DS
锚蛋白亚型-1（TRPA 1）和香草素亚型-1（TRPV 1）的瞬时受体电位通道是结构相关的非选择性阳离子通道，其显示出对钙的高渗透性。以往的研究表明，TRP通道在心血管动力学和稳态调节中起着重要作用，但也有助于心血管系统内许多疾病和病症的病理生理学。然而，迄今为止还没有研究确定TRPA 1在原代成年小鼠心室心肌细胞（CM）中的功能表达和/或细胞内定位。虽然TRPV 1参与了心脏功能的调节，但关于TRPV 1在成人CM中的功能表达和定位的信息很少。我们目前的研究表明，TRPA 1和TRPV 1离子通道在CM中在蛋白水平上共表达，并且这两种通道在整个内膜、心肌和心外膜中表达。此外，免疫细胞化学定位表明，这两个通道主要共定位在Z-光盘，costameres和闰盘。此外，特异性TRPA 1和TRPV 1激动剂引起细胞内游离钙浓度（[Ca 2 +]i）的剂量依赖性瞬时升高，在从TRPA 1 −/−和TRPV 1 −/−小鼠获得的CM中消除。类似地，我们观察到当用浓度增加的选择性TRPA 1或TRPV 1通道拮抗剂预处理WT CM时，TRPA 1和TRPV 1激动剂诱导的[Ca 2 +]i增加的剂量依赖性衰减。总之，这些发现证明了TRPA 1和TRPV 1离子通道在新鲜分离的小鼠CM中的功能表达和精确的超微结构定位。TRPA 1和TRPV 1之间的串扰可能在介导心肌中的细胞信号传导事件中是重要的。
Transient receptor potential channels of the ankyrin subtype-1 (TRPA1) and vanilloid subtype-1 (TRPV1) are structurally related, non-selective cation channels that show a high permeability to calcium. Previous studies indicate that TRP channels play a prominent role in the regulation of cardiovascular dynamics and homeostasis, but also contribute to the pathophysiology of many diseases and disorders within the cardiovascular system. However, no studies to date have identified the functional expression and/or intracellular localization of TRPA1 in primary adult mouse ventricular cardiomyocytes (CMs). Although TRPV1 has been implicated in the regulation of cardiac function, there is a paucity of information regarding functional expression and localization of TRPV1 in adult CMs. Our current studies demonstrate that TRPA1 and TRPV1 ion channels are co-expressed at the protein level in CMs and both channels are expressed throughout the endocardium, myocardium and epicardium. Moreover, immunocytochemical localization demonstrates that both channels predominantly colocalize at the Z-discs, costameres and intercalated discs. Furthermore, specific TRPA1 and TRPV1 agonists elicit dose-dependent, transient rises in intracellular free calcium concentration ([Ca2+]i) that are abolished in CMs obtained from TRPA1−/− and TRPV1−/− mice. Similarly, we observed a dose-dependent attenuation of the TRPA1 and TRPV1 agonist-induced increase in [Ca2+]i when WT CMs were pretreated with increasing concentrations of selective TRPA1 or TRPV1 channel antagonists. In summary, these findings demonstrate functional expression and the precise ultrastructural localization of TRPA1 and TRPV1 ion channels in freshly isolated mouse CMs. Crosstalk between TRPA1 and TRPV1 may be important in mediating cellular signaling events in cardiac muscle.