Adult and Developing Zebrafish as Suitable Models for Cardiac Electrophysiology and Pathology in Research and Industry

Abstract

The electrophysiological behavior of the zebrafish heart is very similar to that of the human heart. In fact, most of the genes that codify the channels and regulatory proteins required for human cardiac function have their orthologs in the zebrafish. The high fecundity, small size, and easy handling make the zebrafish embryos/larvae an interesting candidate to perform whole animal experiments within a plate, offering a reliable and low-cost alternative to replace rodents and larger mammals for the study of cardiac physiology and pathology. The employment of zebrafish embryos/larvae has widened from basic science to industry, being of particular interest for pharmacology studies, since the zebrafish embryo/larva is able to recapitulate a complete and integrated view of cardiac physiology, missed in cell culture. As in the human heart, IKr is the dominant repolarizing current and it is functional as early as 48 h post fertilization. Finally, genome editing techniques such as CRISPR/Cas9 facilitate the humanization of zebrafish embryos/larvae. These techniques allow one to replace zebrafish genes by their human orthologs, making humanized zebrafish embryos/larvae the most promising in vitro model, since it allows the recreation of human-organ-like environment, which is especially necessary in cardiac studies due to the implication of dynamic factors, electrical communication, and the paracrine signals in cardiac function.

Drivers of Sinoatrial Node Automaticity in Zebrafish: Comparison With Mechanisms of Mammalian Pacemaker Function

“…The zebrafish is an increasingly important experimental model for the study of cardiac (patho-) physiology ( Gut et al, 2017 ; Stoyek and Quinn, 2018 ; Echeazarra et al, 2021 ). The zebrafish has a fully sequenced genome, which may be altered using standard genetic techniques ( Rafferty and Quinn, 2018 ; Stoyek et al, 2021b ), and almost every cardiac gene has a human ortholog with analogous function ( Howe et al, 2013 ).…”

Hundreds of LncRNAs Display Circadian Rhythmicity in Zebrafish Larvae

“…Our recent study [8] identified 586 and 165 rhythmically expressed lncRNAs in zebrafish pineal gland and zebrafish testis, respectively, and demonstrated that 26 rhythmically expressed lncRNAs are coexpressed in both the zebrafish pineal gland and testis [8]. We hypothesized that a certain number of circadianly expressed larval lncRNAs may be rhythmically/circadianly expressed in zebrafish pineal gland and testis, even though larvae and adult organs exhibit distinct developmental programs [63,64]. Therefore, we compared these circadianly expressed zebrafish larval lncRNAs under DD and LL conditions with those of the pineal gland testis lncRNAs (Figure 7, Supplementary Tables S29-S34) and revealed that under the DD condition, 60 circadianly expressed larval lncRNAs were coexpressed in the pineal gland (Supplementary Table S29), while 39 circadianly expressed larval lncRNAs were coexpressed in the testis (Supplementary Table S30); and nine circadianly expressed larval lncRNAs were coexpressed in both the pineal gland and testis (Figure 7A, Supplementary Table S31).…”

Poria cum Radix Pini Rescues Barium Chloride-Induced Arrhythmia by Regulating the cGMP-PKG Signalling Pathway Involving ADORA1 in Zebrafish

“…The pericardial congestion area and the SV-BA straight line distance were calculated with ImageJ software (version 1.8.0, NIH, USA). Each experimental treatment was repeated three times (Lin et al, 2007;Gut et al, 2017;Echeazarra et al, 2020).…”

“…Ultra-performance liquid chromatography/ quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF-MS) positive and negative detection modes were used to analyse alcohol extracts of PRP, and the main active ingredients were determined (Zhang et al, 2020). In addition, since zebrafish heart have a very similar electrophysiological behaviour to the human heart, thus, it has become a very interesting model for human heart system pathologies researches, like cardiomyopathy, arrhythmia, heart failure, structural and congenital heart disease etc (Gut et al, 2017;Cassar et al, 2020;Echeazarra et al, 2020). Specially, the advantage of zebrafish embryos is transparency which offer a possibility to observe heart physiology and pathology characteristics directly (Matrone et al, 2015;Crowcombe et al, 2016).…”