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

Hearts

Maaike Alaerts¹  Dorien Schepers¹  Bert Vandendriessche¹  Ewa Sieliwonczyk¹  BartL. Loeys¹  Dirk Snyders² 

[1] Center of Medical Genetics, Faculty of Medicine and Health Sciences, University of Antwerp and Antwerp University Hospital, Prins Boudewijnlaan 43/6, 2650 Edegem, Belgium;Laboratory of Molecular, Cellular and Network Excitability, Department of Biomedical Sciences, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Belgium;

关键词: optical mapping;    hiPSC-CM;    zebrafish;    arrhythmia;    channelopathies;   

DOI  :  10.3390/hearts1030018

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown