Optical Mapping in hiPSC-CM and Zebrafish to Resolve Cardiac Arrhythmias

Abstract

Inherited cardiac arrhythmias contribute substantially to sudden cardiac death in the young. The underlying pathophysiology remains incompletely understood because of the lack of representative study models and the labour-intensive nature of electrophysiological patch clamp experiments. Whereas patch clamp is still considered the gold standard for investigating electrical properties in a cell, optical mapping of voltage and calcium transients has paved the way for high-throughput studies. Moreover, the development of human-induced pluripotent stem-cell-derived cardiomyocytes (hiPSC-CMs) has enabled the study of patient specific cell lines capturing the full genomic background. Nevertheless, hiPSC-CMs do not fully address the complex interactions between various cell types in the heart. Studies using in vivo models, are therefore necessary. Given the analogies between the human and zebrafish cardiovascular system, zebrafish has emerged as a cost-efficient model for arrhythmogenic diseases. In this review, we describe how hiPSC-CM and zebrafish are employed as models to study primary electrical disorders. We provide an overview of the contemporary electrophysiological phenotyping tools and discuss in more depth the different strategies available for optical mapping. We consider the current advantages and disadvantages of both hiPSC-CM and zebrafish as a model and optical mapping as phenotyping tool and propose strategies for further improvement. Overall, the combination of experimental readouts at cellular (hiPSC-CM) and whole organ (zebrafish) level can raise our understanding of the complexity of inherited cardiac arrhythmia disorders to the next level.

Automated Patch-Clamp and Induced Pluripotent Stem Cell-Derived Cardiomyocytes: A Synergistic Approach in the Study of Brugada Syndrome

“…Zebrafish ( Danio rerio ) has emerged as an excellent animal model for cardiovascular and basic research, owing to its fully characterised genome, fast development, and larval optical transparency, as well as its low maintenance costs, high reproduction rates, and the fact that it has over 70% genetic homology with humans, including up to 84% of human disease-related genes [ 39 ]. Its short life cycle of three months, from fertilisation to adulthood, further enhances its appeal as a model organism.…”

Real-Time Optical Mapping of Contracting Cardiac Tissues With GPU-Accelerated Numerical Motion Tracking

“…Voltage- or calcium-sensitive optical mapping can resolve electrophysiological wave phenomena in cardiac tissue at high spatial and temporal resolutions ( 1 – 6 ), and can be performed across various spatial scales: in hearts as small as a zebrafish's heart ( 7 – 9 ), in single cardiomyocytes and cell cultures ( 10 – 13 ), and large hearts including human hearts ( 14 ). Optical mapping supersedes other imaging techniques in terms of spatial resolution and provides the advantage of non-contact measurement.…”