Burton Rebecca-Ann B, Tomek Jakub, Ambrosi Christina M, Larsen Hege E, Sharkey Amy R, Capel Rebecca A, Corbett Alexander D, Bilton Samuel, Klimas Aleksandra, Stephens Guy, Cremer Maegan, Bose Samuel J, Li Dan, Gallone Giuseppe, Herring Neil, Mann Edward O, Kumar Abhinav, Kramer Holger, Entcheva Emilia, Paterson David J, Bub Gil
University of Oxford, Department of Pharmacology, Mansfield Road, Oxford OX1 3QT, UK; University of Oxford, Department of Physiology, Anatomy and Genetics, British Heart Foundation Centre of Research Excellence, Parks Road, Oxford OX1 3PT, UK.
University of Oxford, Department of Physiology, Anatomy and Genetics, British Heart Foundation Centre of Research Excellence, Parks Road, Oxford OX1 3PT, UK.
iScience. 2020 Jul 24;23(7):101334. doi: 10.1016/j.isci.2020.101334. Epub 2020 Jul 1.
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.
通过交感神经元进行心脏刺激可能会引发心律失常。我们提出了一些方法来研究神经元与心肌细胞之间的相互作用，这些方法涉及光遗传学选择性探测和全光学电生理学，以便以自动化方式测量活动。在这里，我们展示了对交感神经元进行光学询问及其对宏观心肌细胞网络动力学的影响的实用性，以解决诸如通过神经递质释放进行肾上腺素能刺激的影响、神经元数量对心脏行为的影响以及光遗传学在体外机制研究中的适用性等研究目标。由于心律失常是涉及数百万个细胞协调活动的突发行为，我们在宏观尺度上进行成像以捕捉复杂的动力学。我们表明，神经元可以根据其诱导活动降低或增加培养物中的波稳定性和折返活动——这一发现可能有助于我们理解在实验和临床研究中经常出现的相互矛盾的结果。
