Optogenetic modulation of cardiac action potential properties may prevent arrhythmogenesis in short and long QT syndromes

Pro-arrhythmic effects of gain-of-function potassium channel mutations in the short QT syndrome

“…While the immaturity of iPSC-CMs and consequent spontaneous electrical activity at present impose some limitations on the interpretation of findings using patient-derived iPSC-CMs, at the single cell level at least, the lack of a stable resting potential can be remedied through electronic I K1 application with dynamic clamp [64,113,143]. The development of improved maturation approaches will ultimately be of high value in the employment of iPSC-CMs, not least in the interrogation of patient-specific treatment approaches and in the further exploration of novel approaches to modulating repolarization, such as miRNA treatment and optogenetics [144][145][146]. A recent systematic literature review has suggested the existence of some sex differences in SQTS features [147], specifically a predominance of syncope among males and a higher risk of royalsocietypublishing.org/journal/rstb Phil.…”

Holographic optogenetic stimulation with calcium imaging as an all optical tool for cardiac electrophysiology

“…Liquid crystal SLMs have slower switching rates but projection of multiple holographic spots generated by this SLM can also be time-gated with DMDs for faster rate of selective switching of light patterns [39]. In most optogenetic applications especially in cardiac systems, DMDs have been used for binary amplitude modulation [18][19][20]37,[40][41][42]. However, for focusing inside the biological tissue using techniques such as digital phase conjugation or adaptive optics, ferroelectric SLMs exhibit twice higher signal to background noise ratio compared with binary amplitude-based DMDs [25,43].…”

“…Burton et al have demonstrated that optogenetics can be used to control chirality of macroscopic spiral waves using patterned light [20]. Studies using parallel light actuation combined with imaging have contributed to our understanding in designing effective strategies to effectively extinguish fibrillation in abnormal cardiac models [37]. Conduction blocks using patterned light to defibrillate whole mouse hearts [18] or in ChR2 expressing cardiomyocyte monolayers [41,42] show promise in using novel light patterns for low-energy defibrillation.…”

“…Therefore, cardiac action potential is accompanied by rapid increase in cytosolic Ca 2+ which can be visualized by calcium imaging. If the light spectral bandwidth (598-613 nm) to excite Cal-630 also photoactivates ChR2, we expect that the continuous illumination of the Cal-630 excitation light will clamp the membrane potential of the cells to a depolarization state and will completely suppress or reduce occurrences of spontaneous action potential [37]. Hence, to confirm that Cal-630 can be used to visualize action potential during optogenetic stimulation with minimal cross-talk, we compared the number of spontaneous calcium peaks for unmodified HL1 cells and HL1-ChR2 cells.…”

Targeted therapies in genetic dilated and hypertrophic cardiomyopathies: from molecular mechanisms to therapeutic targets. A position paper from the Heart Failure Association (HFA) and the Working Group on Myocardial Function of the European Society of Cardiology (ESC)

“…112 The next frontier in tissue engineering will focus on establishing multi-cellular cardiac-like structures (for example through self-organization in case of cardiac organoids 112,113 ) and on incorporating anatomical structural features through the use of organ decellularization/recellularization or three-dimensional bio-printing strategies 114 (Figure 5). Finally, innovative methodologies have been developed to characterize and modulate the functional properties of the hiPSC-based cardiomyopathy models [115][116][117] (Figure 5). These diverse methodologies, focusing on characterizing the electrophysiological and mechanical properties at both the cellular 111 and tissue levels, 106,112,117 can be tailored to derive detailed pathophysiological mechanistic insights into various disease pathogenesis as well as scaled up for high throughput pharmacological studies.…”