Evolving Cardiac Conduction Phenotypes in Developing Zebrafish Larvae: Implications to Drug Sensitivity

Abstract

Cardiac arrhythmias include problems with impulse formation and/or conduction abnormalities. Zebrafish (Danio rerio) is an emerging model system for studying the cardiac conduction system. However, real-time recording of the electrocardiogram remains a challenge. In the present study, we assessed the feasibility of recording electrical cardiogram (ECG) signals from the zebrafish larvae using the micropipette electrodes, and demonstrated the dynamic changes in ECG signals and their sensitivity to Amiodarone during the developmental stages. We observed that ECG signals revealed P waves and QRS complexes at 7 days postfertilization (dpf). T waves started to develop at 14 dpf. Distinct P waves, QRS complexes, and T waves were similar to those of adult zebrafish at 35 dpf, accompanied by a statistically significant decrease in QRS intervals (from 256 ± 16 ms at 7 dpf to 54 ± 6 ms, p < 0.01, n = 5). In response to Amiodarone, ECG signals showed QRS prolongation from 7 to 35 dpf (p < 0.05, n = 5). Hence, micropipette electrodes can be applied to detect evolving ECG signals from the developing zebrafish larvae, thus providing a noninvasive and nonparalyzing approach to investigate cardiac conduction phenotypes in response to genetic, epigenetic, or pharmacologic perturbation.