Cardiac optogenetics

Abstract

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. channelrhodopsin; light-sensitive ion channels; optical mapping THIS ARTICLE is part of a collection on Physiological Basis of Cardiovascular Cell and Gene Therapies. Other articles appearing in this collection, as well as a full archive of all collections, can be found online at http://ajpheart.physiology.org/. Background

Optogenetic determination of the myocardial requirements for extrasystoles by cell type-specific targeting of ChannelRhodopsin-2

“…ChR2 exhibits fast and reversible activation kinetics (in the order of milliseconds) that is instrumental to drive reliable trains of high-frequency action potentials in vivo. Optogenetics is widely used in neuroscience to modulate neuronal circuits in in vivo models (29)(30)(31) and has been proposed as an attractive tool to control cardiomyocyte membrane potential (32)(33)(34)(35)(36). In cardiac research, optogenetics is still in the very early stages and has mainly been applied to in vitro and regenerative medicine studies (37)(38)(39)(40)(41).…”

Cardiac Arrhythmias: Mechanistic Knowledge and Innovation from Computer Models

“…Cardiac optogenetics is an emerging field that involves inserting light-sensitive ion channels (opsins) in heart tissue to enable control of bioelectric behavior with illumination instead of electric current [49,131]. This technology is poised to open a new avenue for the development of safe and effective anti-arrhythmia therapies by enabling the evocation of spatiotemporally precise responses in targeted cells or tissues.…”

Negative Curvature and Control of Excitable Biological Media

“…10.4. Such "optogenetic" actuation (stimulation or suppression of activity by light) can be achieved after genetic modification of the tissue using light-sensitive ion channels or pumps, reviewed in [33,34]. Optogenetic perturbation offers superior options for active control of cardiac dynamics compared to electrical or chemical means of control, as it can achieve better spatiotemporal resolution, can be cell-specific (by the virtue of genetic targeting of a particular cell type), and can be bi-directional in terms of polarity of the induced changes in membrane voltage, i.e.…”