Extracellular and Intracellular Angiotensin II Regulate the Automaticity of Developing Cardiomyocytes via Different Signaling Pathways.
Extracellular and Intracellular Angiotensin II Regulate the Automaticity of Developing Cardiomyocytes via Different Signaling Pathways.
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细胞外和细胞内血管紧张素 II 通过不同信号通路调节心肌细胞发育的自动化
DOI：
10.3389/fmolb.2021.699827
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发表时间：
2021
影响因子：
5
通讯作者：
Tsang SY
中科院分区：
文献类型：
--
作者：
Qi Z;Wang T;Chen X;Wong CK;Ding Q;Sauer H;Chen ZF;Long C;Yao X;Cai Z;Tsang SY
血管紧张素II（Angiotensin II，Ang II）在调节多种生理过程中起重要作用。然而，对于细胞内是否存在血管紧张素Ⅱ（iAng Ⅱ），iAng Ⅱ是否能调节早期分化心肌细胞的自律性，以及其机制尚不清楚。在这里，iAng II检测免疫细胞化学和超高效液相色谱结合电喷雾电离三重四极杆串联质谱在小鼠胚胎干细胞衍生的心肌细胞（mESC-CMs）和新生大鼠心室肌细胞。AT 1 R-YFP在mESC-CM中的表达揭示了Ang II 1型受体位于表面膜，而Ang II 2型受体（AT 2 R）的免疫染色揭示了AT 2 R主要位于细胞核和肌浆网。虽然细胞外的血管紧张素II增加自发动作电位（AP），双膜片钳显示，细胞内输送的血管紧张素II或AT 2 R激活剂C21减少自发AP。有趣的是，iAng II被发现减少咖啡因诱导的自发AP增加和咖啡因诱导的钙释放，表明iAng II通过AT 2 R和ryanodine受体介导的途径减少自发AP。这是第一项提供iAng II在调节ESC-CM的自律性行为中的存在和功能的证据的研究，因此可能阐明iAng II在命运决定中的作用。
Angiotensin II (Ang II) plays an important role in regulating various physiological processes. However, little is known about the existence of intracellular Ang II (iAng II), whether iAng II would regulate the automaticity of early differentiating cardiomyocytes, and the underlying mechanism involved. Here, iAng II was detected by immunocytochemistry and ultra-high performance liquid chromatography combined with electrospray ionization triple quadrupole tandem mass spectrometry in mouse embryonic stem cell–derived cardiomyocytes (mESC-CMs) and neonatal rat ventricular myocytes. Expression of AT1R-YFP in mESC-CMs revealed that Ang II type 1 receptors were located on the surface membrane, while immunostaining of Ang II type 2 receptors (AT2R) revealed that AT2R were predominately located on the nucleus and the sarcoplasmic reticulum. While extracellular Ang II increased spontaneous action potentials (APs), dual patch clamping revealed that intracellular delivery of Ang II or AT2R activator C21 decreased spontaneous APs. Interestingly, iAng II was found to decrease the caffeine-induced increase in spontaneous APs and caffeine-induced calcium release, suggesting that iAng II decreased spontaneous APs via the AT2R- and ryanodine receptor–mediated pathways. This is the first study that provides evidence of the presence and function of iAng II in regulating the automaticity behavior of ESC-CMs and may therefore shed light on the role of iAng II in fate determination.
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影响因子：
4.5
作者：
Padia, Shetal H.;Carey, Robert M.
通讯作者：
Carey, Robert M.
影响因子：
13.5
作者：
Jones ES;Vinh A;McCarthy CA;Gaspari TA;Widdop RE
通讯作者：
Widdop RE
影响因子：
3.5
作者：
Gallinat, S;Busche, S;Unger, T
通讯作者：
Unger, T
影响因子：
20.1
作者：
Lakatta EG;Maltsev VA;Vinogradova TM
通讯作者：
Vinogradova TM
影响因子：
1.9
作者：
Muller, J;Corodimas, KP;LeDoux, JE
通讯作者：
LeDoux, JE