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Flexible microelectrode arrays to interface epicardial electrical signals with intracardial calcium transients in zebrafish hearts

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Abstract

The zebrafish (Danio rerio) is an emerging genetic model for regenerative medicine. In humans, myocardial infarction results in the irreversible loss of cardiomyocytes. However, zebrafish hearts fully regenerate after a 20% ventricular resection, without either scarring or arrhythmias. To study this cardiac regeneration, we developed implantable flexible multi-microelectrode membrane arrays that measure the epicardial electrocardiogram signals of zebrafish in real-time. The microelectrode electrical signals allowed for a high level of both temporal and spatial resolution (~20 μm), and the signal to noise ratio of the epicardial ECG was comparable to that of surface electrode ECG (7.1 dB vs. 7.4 dB, respectively). Processing and analysis of the signals from the microelectrode array demonstrated distinct ECG signals: namely, atrial conduction (P waves), ventricular contraction (QRS), and ventricular repolarization (QT interval). The electrical signals were in synchrony with optically measured Calcium concentration gradients in terms of d[Ca2+]/dt at both whole heart and tissue levels. These microelectrodes therefore provide a real-time analytical tool for monitoring conduction phenotypes of small vertebral animals with a high temporal and spatial resolution.

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Acknowledgement

The authors would like to express gratitude for Dr. Fuhua Chen from UCLA School of Medicine for providing the Calcium voltage mapping. This project was supported by the American Heart Association Pre-Doctoral Fellowship (11PRE7370088) (FY), National Institutes of Health, National Heart Lung and Blood Institute (HL083015) (TKH), HL091302 (TKH), (HL104239) (NCC) and National Institute of Child Health & Human Development (HD069305) (NCC and TKH).

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Authors and Affiliations

  1. Biomedical Engineering and Cardiovascular Medicine, University of Southern California, Los Angeles, CA, USA

    Fei Yu, Jie Gu, Katherine L. Quigley & Tzung K. Hsiai

  2. Electrical Engineering, California Institute of Technology, Pasadena, CA, USA

    Yu Zhao & Yu-Chong Tai

  3. Department of Medicine, Division of Cardiology, University of California, San Diego, La Jolla, CA, 92093-0613J, USA

    Neil C. Chi

  4. Cardiovascular Engineering Research Core, Biomedical Engineering and Cardiovascular Medicine, University of Southern California, Los Angeles, CA, 90089, USA

    Tzung K. Hsiai

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  1. Fei Yu
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  2. Yu Zhao
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  3. Jie Gu
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  4. Katherine L. Quigley
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  5. Neil C. Chi
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  6. Yu-Chong Tai
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  7. Tzung K. Hsiai
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Correspondence to Tzung K. Hsiai.

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Yu, F., Zhao, Y., Gu, J. et al. Flexible microelectrode arrays to interface epicardial electrical signals with intracardial calcium transients in zebrafish hearts. Biomed Microdevices 14, 357–366 (2012). https://doi.org/10.1007/s10544-011-9612-9

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  • DOI: https://doi.org/10.1007/s10544-011-9612-9

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