Angiotensin II controls the automaticity of embryonic stem cell-derived cardiomyocytes by autocrine signaling

Physiology 2016 (Dublin, Ireland) (2016) Proc Physiol Soc 37, PCB095

Poster Communications: Angiotensin II controls the automaticity of embryonic stem cell-derived cardiomyocytes by autocrine signaling

Z. Qi1, C. Wong1, X. Yao2, S. Tsang1

1. School of Life Sciences, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong. 2. School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, Hong Kong.

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Early differentiating cardiomyocytes, distinct from adult cardiomyocytes, generate spontaneous calcium transients and action potentials. This automaticity resembles what is observed in sinoatrial nodal cells. The underlying mechanism of automaticity is not fully understood. In this study, early differentiating mouse embryonic stem cell-derived cardiomyocytes (mESC-CMs) are used to study automaticity. The objectives of this study were: 1) to investigate if mESC-CMs express the components of the renin-angiotensin system (RAS); 2) to investigate if blocking the angiotensin II (Ang II) receptor would affect the spontaneous calcium transients and action potentials of mESC-CMs. By immunocytochemistry, our results showed that mESC-CMs express several components of the RAS, including the angiotensin converting enzyme, chymase, Ang II type 1 receptors (AT1R) and Ang II type 2 receptors (AT2R). Interestingly, by calcium imaging and current patch clamp, we found that addition of AT1R blocker losartan alone decreased both the calcium transients and action potentials of mESC-CMs. Our results suggest that mESC-CMs may synthesize Ang II intracellularly; the Ang II in turn controls the automaticity positively in an autocrine manner. Further study would be required to dissect out the role of both AT1R and AT2R in controlling the automaticity of mESC-CMs. This study will yield important information on the mechanism underlying the automaticity of cardiomyocytes.



Where applicable, experiments conform with Society ethical requirements.

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