Evolution of Action Potential Propagation and Repolarization in Cultured Neonatal Rat Ventricular Myocytes

Authors

  • GIDEON MEIRY M.Sc.,

    1. Rappaport Family Institute for Research in the Medical Sciences, Bruce Rappaport Faculty of Medicine, The Bernard Katz Center for Cell Biophysics, Technion-Israel Institute of Technology, Haifa, Israel
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    • §

      The first two authors contributed equally to this work.

  • YOTAM REISNER M.Sc.,

    1. Rappaport Family Institute for Research in the Medical Sciences, Bruce Rappaport Faculty of Medicine, The Bernard Katz Center for Cell Biophysics, Technion-Israel Institute of Technology, Haifa, Israel
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    • §

      The first two authors contributed equally to this work.

  • YAIR FELD M.Sc.,

    1. Rappaport Family Institute for Research in the Medical Sciences, Bruce Rappaport Faculty of Medicine, The Bernard Katz Center for Cell Biophysics, Technion-Israel Institute of Technology, Haifa, Israel
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  • STANISLAV GOLDBERG,

    1. Rappaport Family Institute for Research in the Medical Sciences, Bruce Rappaport Faculty of Medicine, The Bernard Katz Center for Cell Biophysics, Technion-Israel Institute of Technology, Haifa, Israel
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  • MICHAEL ROSEN M.D.,

    1. Center for Molecular Therapeutics, New York
    2. Department of Pharmacology, College of Physicians and Surgeons of Columbia University, New York, New York
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  • NOAM ZIV Ph.D.,

    1. Rappaport Family Institute for Research in the Medical Sciences, Bruce Rappaport Faculty of Medicine, The Bernard Katz Center for Cell Biophysics, Technion-Israel Institute of Technology, Haifa, Israel
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  • OFER BINAH Ph.D.

    1. Rappaport Family Institute for Research in the Medical Sciences, Bruce Rappaport Faculty of Medicine, The Bernard Katz Center for Cell Biophysics, Technion-Israel Institute of Technology, Haifa, Israel
    2. Center for Molecular Therapeutics, New York
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  • This research was supported by grants from the U.S.-Israel Binational Science Foundation (Grant 180–331) and the Bugher Foundation to Drs. Binah and Rosen. This research also was funded by the Minerva Foundation, the Technion V.P.R. Fund for The Promotion of Research at the Technion, and the Rappaport Institute to Dr. Binah, and by USPHS-NHLBI Grant HL-28958 to Dr. Rosen.

Address for correspondence: Ofer Binah, Ph.D., Rappaport Institute, P.O.B. 9697, Haifa 31096, Israel. Fax: 972-4-8513919; E-mail: binah@tx.technion.ac.il

Abstract

Maturation of Cultured Neonatal Rat Ventricular Myocytes. Introduction: Cultured neonatal rat ventricular myocytes (NRVM) reestablish gap junctions as they form synchronously and spontaneously beating monolayers, thus providing a useful model for studying activation and repolarization.

Methods and Results: We used the multielectrode array data acquisition system with 60 unipolar electrodes to investigate the functional organization of cultured NRVM, by determining propagation and repolarization patterns. Activation maps were constructed from the local activation times at each electrode. During days 3 to 8 in culture, QRS amplitude and dV/dtmax increased with age. Concomitantly, with the culture maturation, QT interval (representing action potential duration) decreased, and T wave amplitude and slopes of the T wave ascending and descending limbs progressively increased. The changes in conduction velocity were different than those of the electrogram properties, slightly increasing during the first 3 to 5 days and gradually declining toward day 8 in culture.

Conclusion: Establishment of uniform activation patterns in spontaneously firing or driven myocytes in monolayer cultures is accompanied by organization of activation and repolarization whose evolution appears in concert with that of a mature connexin43 staining pattern. The experimental techniques developed in this study provide useful tools to investigate the complex relations among gap junctions, conduction velocity, and propagation patterns, as well as a means to learn how gap junctional remodeling under pathophysiologic conditions predisposes the myocardium to arrhythmias.

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