Optical Interrogation of Sympathetic Neuronal Effects on Macroscopic Cardiomyocyte Network Dynamics
Optical Interrogation of Sympathetic Neuronal Effects on Macroscopic Cardiomyocyte Network Dynamics
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DOI：
10.1016/j.isci.2020.101334
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发表时间：
2020-07-24
期刊：
影响因子：
5.8
通讯作者：
Bub, Gil
中科院分区：
文献类型：
--
作者：
Burton, Rebecca-Ann B.;Tomek, Jakub;Bub, Gil
经由交感神经元的心脏刺激可能潜在地触发心律失常。我们提出了研究神经元-心肌细胞相互作用的方法，包括光遗传学选择性探测和全光学电生理学，以自动方式测量活动。在这里，我们展示了交感神经元的光学询问的效用及其对宏观心肌细胞网络动力学的影响，以解决研究目标，如肾上腺素能刺激通过释放神经递质的影响，神经元数量对心脏行为的影响，以及光遗传学在体外研究中的适用性。由于心律失常是涉及数百万细胞协调活动的紧急行为，因此我们在宏观尺度上成像以捕获复杂的动态。我们发现，神经元可以减少和增加波的稳定性和折返活动，在文化取决于他们的诱导活动，这一发现可能有助于我们理解在实验和临床研究中看到的往往相互矛盾的结果。
Cardiac stimulation via sympathetic neurons can potentially trigger arrhythmias. We present approaches to study neuron-cardiomyocyte interactions involving optogenetic selective probing and all-optical electrophysiology to measure activity in an automated fashion. Here we demonstrate the utility of optical interrogation of sympathetic neurons and their effects on macroscopic cardiomyocyte network dynamics to address research targets such as the effects of adrenergic stimulation via the release of neurotransmitters, the effect of neuronal numbers on cardiac behavior, and the applicability of optogenetics in mechanistic in vitro studies. As arrhythmias are emergent behaviors that involve the coordinated activity of millions of cells, we image at macroscopic scales to capture complex dynamics. We show that neurons can both decrease and increase wave stability and re-entrant activity in culture depending on their induced activity-a finding that may help us understand the often conflicting results seen in experimental and clinical studies.