![]() ![]() Although lacking the phase 1 repolarization stage, the zebrafish cardiac AP contains all other phases present in the human cardiac AP. Additionally, the zebrafish cardiac action potential (AP) is similar to the human cardiac AP. Notably, zebrafish resting heart rate ( Vornanen and Hassinen, 2016) is much closer to the human rate than that of traditional model organisms used to examine cardiac electrophysiology, such as mice (500-700 bpm) ( Ho et al., 2011). Although its two-chambered anatomy differs strikingly from that of the four-chambered human heart, zebrafish cardiac electrophysiology is comparable to that of the human cardiac system ( Fig. 1A) ( Goldberger et al., 2000). The zebrafish cardiovascular system includes a two-chambered heart (atrium and ventricle) and the bulbus arteriosus, a functional aorta surrogate structure ( Vornanen and Hassinen, 2016). The zebrafish ( Danio rerio) is an excellent vertebrate experimental model system owing to its short generation time, low maintenance cost, large clutch sizes, ease with which it can be manipulated genetically ( Irion et al., 2014 Moore et al., 2012 Varshney and Burgess, 2014), extensive developmental characterization and optical transparency ( Gut et al., 2017). This has important clinical applications, because therapeutics targeting these regulatory components that modulate the electrical activity of the heart can be used as treatments for human diseases. We can begin to unravel the specific regulatory components by examining the basic biology underlying heart rate and cardiac electrophysiology to develop a framework to dissect related abnormalities. Although it is appreciated that alterations in cardiac electrophysiology are hallmarks and/or risk factors for a variety of human diseases ( Ashar et al., 2018 Arking et al., 2014 Mizusawa and Wilde, 2012 Ntalla et al., 2020 Pflaumer et al., 2020 Schwartz et al., 2012 van der Harst et al., 2016), the processes that regulate it are less understood. The waves in an ECG are a byproduct of atrial and ventricular depolarizations and repolarizations, and the intervals between the waves provide insight into the timing of these events. These results highlight our pipeline as a robust approach to evaluate zebrafish models of human cardiac electrophysiological phenotypes.Ĭardiac electrophysiology involves the precise coordination of the electrical activity of the heart, which can be visualized and measured using the electrocardiogram (ECG). With this framework, we characterize the effect of the class I anti-arrhythmic drug flecainide acetate on adults, provide support for the impact of a Long QT syndrome model, and establish power calculations for this and other studies. ![]() We evaluate normal ECG trait variation, revealing highly reproducible intervals and wave amplitude variation largely driven by recording artifacts, and identify sex and body size as potential confounders to PR, QRS and QT intervals. Thus, we developed a novel platform to ensure high-quality recording of in vivo subdermal adult zebrafish ECGs and zebrafish ECG reading GUI (zERG), a program to acquire measurements from traces that commercial software cannot examine owing to erroneous peak calling. Current zebrafish ECG collection strategies have not adequately addressed the consistent acquisition of high-quality traces or sources of phenotypic variation that could obscure data interpretation. Clinically pertinent electrocardiogram (ECG) data from model systems, such as zebrafish, are crucial for illuminating factors contributing to human cardiac electrophysiological abnormalities and disease. ![]()
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