Department of Biomedical Engineering, Department of Physiology and Biophysics, and Institute for Molecular Cardiology, Stony Brook University, Stony Brook, New York, USA.
Am J Physiol Heart Circ Physiol. 2013 May;304(9):H1179-91. doi: 10.1152/ajpheart.00432.2012. Epub 2013 Mar 1.
Optogenetics is an emerging technology for optical interrogation and control of biological function with high specificity and high spatiotemporal resolution. Mammalian cells and tissues can be sensitized to respond to light by a relatively simple and well-tolerated genetic modification using microbial opsins (light-gated ion channels and pumps). These can achieve fast and specific excitatory or inhibitory response, offering distinct advantages over traditional pharmacological or electrical means of perturbation. Since the first demonstrations of utility in mammalian cells (neurons) in 2005, optogenetics has spurred immense research activity and has inspired numerous applications for dissection of neural circuitry and understanding of brain function in health and disease, applications ranging from in vitro to work in behaving animals. Only recently (since 2010), the field has extended to cardiac applications with less than a dozen publications to date. In consideration of the early phase of work on cardiac optogenetics and the impact of the technique in understanding another excitable tissue, the brain, this review is largely a perspective of possibilities in the heart. It covers the basic principles of operation of light-sensitive ion channels and pumps, the available tools and ongoing efforts in optimizing them, overview of neuroscience use, as well as cardiac-specific questions of implementation and ideas for best use of this emerging technology in the heart.
光遗传学是一种新兴的技术,可实现对生物功能的光学检测和控制,具有高度特异性和高时空分辨率。通过使用微生物视蛋白(光门控离子通道和泵)对哺乳动物细胞和组织进行相对简单且耐受性良好的遗传修饰,就可以使其对光产生反应。这些修饰可以实现快速和特异性的兴奋或抑制反应,与传统的药理学或电刺激方法相比具有明显的优势。自 2005 年首次在哺乳动物细胞(神经元)中证明其具有实用性以来,光遗传学激发了大量的研究活动,并为神经回路的剖析和对健康和疾病状态下大脑功能的理解提供了许多应用,应用范围从体外到行为动物实验。直到最近(自 2010 年以来),该领域才扩展到心脏应用,目前仅有不到十二篇相关出版物。鉴于心脏光遗传学的工作仍处于早期阶段,并且该技术在理解另一种可兴奋组织(大脑)方面具有重要影响,因此本文主要是从心脏的角度来探讨光遗传学的可能性。它涵盖了光敏感离子通道和泵的基本工作原理、可用于优化它们的现有工具和正在进行的努力、神经科学应用概述,以及心脏实施的具体问题和最佳利用这种新兴技术的思路。