Presentation description

Atrial fibrillation is a cardiac arrhythmia characterized by an irregular heartbeat in the atrial chambers of the heart. Our previous work has identified the Nuclear Factor of Activated T-cells (NFATC1) as a novel atrial fibrillation susceptibility gene for familiar atrial fibrillation (phenotype appearing at <40 years old). NFATC1 is known to be involved in cardiac development, but the link to arrhythmias has not been previously established. Using CRISPR/Cas9 we generated a nfact1 knock-out (KO) zebrafish transgenic line that showed an increase presence of arrhythmogenic events and a sudden death phenotype in juvenile fish. Our current objective is to determine whether the absence of nfatc1 influences heart function and response to stress in zebrafish embryos (48- to 120-hours post-fertilization (hpf)). Wild type (WT) and nfact1 KO larvae were submerged in egg water and their base heart rate was measured using videorecording and analyzed with ImageJ software. Larvae heart rate was then measured in the presence of 100 uM of isoproterenol to test their response to adrenergic stimulation. We observed that the heart rates of the nfatc1 KO fish follow the expected increased with age, but were not statistically different from the wild type fish of the same developmental stage (ANOVA, p=0.86 for genotype, p<0.0001 for hpf). When the larvae were exposed to isoproterenol, their increase in heart rate was independent of genotype (ANOV, p=0.55). Furthermore, the addition of isoproterenol did not elicit arrhythmias in either genotype. Taking as a whole, these results suggest that nfatc1 does not affect heart rate or response to adrenergic stimulation in early developmental stages. These findings suggest that an impaired gene function may be more relevant in the juvenile heart, which is in line with an early onset atrial fibrillation phenotype observed in humans.