Patterned Illumination Techniques in Optogenetics: An Insight Into Decelerating Murine Hearts

Abstract

Much has been reported about optogenetic based cardiac arrhythmia treatment and the corresponding characterization of photostimulation parameters, but still, our capacity to interact with the underlying spatiotemporal excitation patterns relies mainly on electrical and/or pharmacological approaches. However, these well-established treatments have always been an object of somehow heated discussions. Though being acutely life-saving, they often come with potential side-effects leading to a decreased functionality of the complex cardiac system. Recent optogenetic studies showed the feasibility of the usage of photostimulation as a defibrillation method with comparatively high success rates. Although, these studies mainly concentrated on the description as well as on the comparison of single photodefibrillation approaches, such as locally focused light application and global illumination, less effort was spent on the description of excitation patterns during actual photostimulation. In this study, the authors implemented a multi-site photodefibrillation technique in combination with Multi-Lead electrocardiograms (ECGs). The technical connection of real-time heart rhythm measurements and the arrhythmia counteracting light control provides a further step toward automated arrhythmia classification, which can lead to adaptive photodefibrillation methods. In order to show the power effectiveness of the new approach, transgenic murine hearts expressing channelrhodopsin-2 ex vivo were investigated using circumferential micro-LED and ECG arrays. Thus, combining the best of two methods by giving the possibility to illuminate either locally or globally with differing pulse parameters. The optical technique presented here addresses a number of challenges of technical cardiac optogenetics and is discussed in the context of arrhythmic development during photostimulation.

Optical Control of Cardiac Electrophysiology by the Photochromic Ligand AB2

“…In part, we attribute the reduction in VA frequency to a decrease in amplitude consequently challenging the automated detection algorithm. However, weighted VA frequencies within the first minute were in good agreement with values ranging from 15 - 30 Hz as reported in the literature [16].…”

“…S6, n = 5), whereas only a single heart remained in a VA. It is important to note that the frequencies of SR in Langendorff-perfused mouse hearts ranged between 5 - 7 Hz, which is in good agreement to the reported literature [16]. AB2 may hence prove useful not only to limit VA frequencies but also to effectively terminate stably running VA.…”

“…Finally, we explored photoswitching of AB2 as a potential means to terminate VA. Stable runs of VA were induced in the Langendorff-perfused mouse heart by either low [K + ] e of 2 mM alone or combined with electrical burst or S1-S2 stimulation (see Methods) as shown before [10, 11, 16, 21, 65]. VAs were considered stable when they lasted > 5 min without spontaneous termination.…”

Optogenetic manipulation of cardiac electrical dynamics using sub-threshold illumination: dissecting the role of cardiac alternans in terminating rapid rhythms

“…Following the tremendous advances achieved in neuroscience, optogenetics has been successfully extended to cardiac research [13]. Optogenetics-based strategies have been proposed as alternatives to wired electrical stimulation for cardiac pacing [6,30] and cardioversion [4,5,9,11,16,31,36,38]. Moreover, optogenetics recently emerged as a robust tool for investigating wave dynamics in cardiac tissue, studying the mechanisms underlying the induction, maintenance and control of cardiac arrhythmias [7,12,14,40].…”