Cardiac optogenetics: shining light on signaling pathways

Siri Leemann, Franziska Schneider-Warme, Sonja Kleinlogel
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Abstract

In the early 2000s, the field of neuroscience experienced a groundbreaking transformation with the advent of optogenetics. This innovative technique harnesses the properties of naturally occurring and genetically engineered rhodopsins to confer light sensitivity upon target cells. The remarkable spatiotemporal precision offered by optogenetics has provided researchers with unprecedented opportunities to dissect cellular physiology, leading to an entirely new level of investigation. Initially revolutionizing neuroscience, optogenetics quickly piqued the interest of the wider scientific community, and optogenetic applications were expanded to cardiovascular research. Over the past decade, researchers have employed various optical tools to observe, regulate, and steer the membrane potential of excitable cells in the heart. Despite these advancements, achieving control over specific signaling pathways within the heart has remained an elusive goal. Here, we review the optogenetic tools suitable to control cardiac signaling pathways with a focus on GPCR signaling, and delineate potential applications for studying these pathways, both in healthy and diseased hearts. By shedding light on these exciting developments, we hope to contribute to the ongoing progress in basic cardiac research to facilitate the discovery of novel therapeutic possibilities for treating cardiovascular pathologies.

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心脏光遗传学:照亮信号通路
本世纪初,随着光遗传学的出现,神经科学领域经历了一场划时代的变革。这项创新技术利用天然存在和基因工程改造的视紫红质的特性,赋予靶细胞对光的敏感性。光遗传学所提供的卓越时空精度为研究人员提供了前所未有的机会来剖析细胞生理学,从而将研究推向了一个全新的高度。光遗传学最初给神经科学带来了革命性的变化,但很快就引起了更广泛科学界的兴趣,并将光遗传学的应用扩展到心血管研究领域。过去十年间,研究人员利用各种光学工具观察、调节和引导心脏可兴奋细胞的膜电位。尽管取得了这些进展,但实现对心脏内特定信号通路的控制仍是一个难以实现的目标。在此,我们回顾了适用于控制心脏信号通路的光遗传学工具,重点是 GPCR 信号通路,并描述了在健康和患病心脏中研究这些通路的潜在应用。我们希望通过揭示这些令人兴奋的发展,推动心脏基础研究的不断进步,从而促进发现治疗心血管疾病的新疗法。
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