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(Circulation Research. 2007;101:484.)
© 2007 American Heart Association, Inc.

Cellular Biology

Electrophysiological Maturation and Integration of Murine Fetal Cardiomyocytes After Transplantation

Marcel Halbach, Kurt Pfannkuche, Frank Pillekamp, Agnieszka Ziomka, Tobias Hannes, Michael Reppel, Juergen Hescheler, Jochen Müller-Ehmsen

From the Department III of Internal Medicine (M.H., A.Z., J.M.-E.), Institute of Neurophysiology (M.H., K.P., F.P., T.H., M.R., J.H.), and Department of Pediatric Cardiology (F.P., T.H.), University of Cologne, Germany; and Medizinische Klinik II (M.R.), University of Schleswig–Holstein, Campus Luebeck, Germany.

Correspondence to Priv-Doz Dr Jochen Müller-Ehmsen, Department III of Internal Medicine, University of Cologne, Kerpener Str. 62, D-50937 Cologne, Germany. E-mail muller.ehmsen{at}uni-koeln.de, and Prof Dr Juergen Hescheler, Institute of Neurophysiology, University of Cologne, Robert-Koch Str. 39, D-50931 Cologne, Germany. E-mail j.hescheler@uni-koeln.de

In the present study, we investigated the electrophysiological maturation and integration of immature cardiomyocytes after transplantation; maturation and integration are essential to achieve the cardiac regeneration. Murine fetal cardiomyocytes (FCMs) (d12.5-d15.5) expressing enhanced green fluorescent protein under the control of the -actin promoter were injected into cryoinjured areas and adjacent myocardium of cryoinjured mouse ventricles. Viable short axis tissue slices (thickness, 150 µm) of the ventricles were prepared 5 to 6 days after transplantation. Glass microelectrodes were used for measurements of action potentials in transplanted FCMs and host cardiomyocytes within the slices. Stimulation at frequencies of up to 10 Hz was performed via a unipolar electrode placed in viable host tissue. Transplanted FCMs could be distinguished clearly from host tissue by their green fluorescence and their electrophysiological properties: maximal upstroke velocity (V_max) was significantly lower and action potential duration at 50% repolarization (APD₅₀) was significantly longer compared with values of adult cardiomyocytes. Transplanted FCMs surrounded by cryoinjured tissue showed spontaneous electrical and contractile activity, which was in no case synchronous with host tissue. V_max and APD₅₀ of these nonintegrated cells matched values of cultivated dissociated FCMs. In contrast, 82% of transplanted FCMs surrounded by viable host tissue were electrically integrated; ie, electrical and contractile activity was synchronous with host tissue and these cells had more mature action potential parameters (significantly higher V_max and shorter APD₅₀) compared with nonintegrated FCMs. In conclusion, electrophysiological maturation and integration of transplanted FCMs depend on an embedment in viable host myocardium. FCMs surrounded by cryoinjured tissue maintain physiological but immature AP properties.

Key Words: cardiac electrophysiology • cardiomyoplasty • coupling • heart slices • maturation

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Electrophysiological Coupling of Transplanted Cardiomyocytes

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Circ. Res. 2007 101: 433-435. [Full Text] [PDF]

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				I. Kehat and L. Gepstein Electrophysiological Coupling of Transplanted Cardiomyocytes Circ. Res., August 31, 2007; 101(5): 433 - 435. [Full Text] [PDF]