Abstract
Optical techniques for recording and manipulating cellular electrophysiology have advanced rapidly in just a few decades. These developments allow for the analysis of cardiac cellular dynamics at multiple scales while largely overcoming the drawbacks associated with the use of electrodes. The recent advent of optogenetics opens up new possibilities for regional and tissue-level electrophysiological control and hold promise for future novel clinical applications. This article, which emerged from the international NOTICE workshop in 20181, reviews the state-of-the-art optical techniques used for cardiac electrophysiological research and the underlying biophysics. The design and performance of optical reporters and optogenetic actuators are reviewed along with limitations of current probes. The physics of light interaction with cardiac tissue is detailed and associated challenges with the use of optical sensors and actuators are presented. Case studies include the use of fluorescence recovery after photobleaching and super-resolution microscopy to explore the micro-structure of cardiac cells and a review of two photon and light sheet technologies applied to cardiac tissue. The emergence of cardiac optogenetics is reviewed and the current work exploring the potential clinical use of optogenetics is also described. Approaches which combine optogenetic manipulation and optical voltage measurement are discussed, in terms of platforms that allow real-time manipulation of whole heart electrophysiology in open and closed-loop systems to study optimal ways to terminate spiral arrhythmias. The design and operation of optics-based approaches that allow high-throughput cardiac electrophysiological assays is presented. Finally, emerging techniques of photo-acoustic imaging and stress sensors are described along with strategies for future development and establishment of these techniques in mainstream electrophysiological research.
Highlights
This has met with some success in both small (Matsuo et al, 2015; Pecha et al, 2019) and large animal models (Gao et al, 2017), but questions remain over the extent of engineered heart tissue (EHT) coupling to native myocardium, as well as the long-term survival of the originally-implanted cells
While similar techniques are being developed in neuroscience, cardiac tissue presents a series of additional challenges related to the highly scattering nature of the myocardium and movement associated with contraction
This article describes some of the fundamentals of physics that underlie optical techniques used to measure and manipulate the electrical activity of the heart
Summary
Our current understanding of myocardial tissue electrophysiology is derived from measurements of action potential features i.e., activation, repolarization, and conduction velocity in myocardial tissue. The gold standard for transmembrane measurements is the sharp microelectrode that gives highresistance access to the intracellular medium at a single point to allow transmembrane voltage recording This is in routine use in isolated tissue preparations (Hicks and Cobbe, 1991; Sicouri and Antzelevitch, 1991; Di Diego et al, 2013) but has limitations including: (i) maintenance of the delicate high-resistance intracellular access in an actively contracting tissue; (ii) the technical challenge associated with maintaining multiple simultaneous intracellular measurements to follow propagation; (iii) the difficulty in applying this technique to record transmural electrophysiology in an intact ventricular wall that in larger mammals can reach 1–2 cm thick. Significant sections of this review are devoted to the basic physical principles associated with light/tissue interaction
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