Evolution of action potential propagation and repolarization in cultured neonatal rat ventricular myocytes

Maturation of Cultured Neonatal Rat Ventricular Myocytes. Introduction: Cul tured neonatal rat ventricular myocytes (NRVM) reestablish gap junctions as they form synchronously and spontaneously beating monolayers, thus providi ng a useful model for studying activation and repolarization. Methods and Results: We used the multielectrode array data acquisition syst em with 60 unipolar electrodes to investigate the functional organization o f cultured NRVM, by determining propagation and repolarization patterns. Ac tivation maps were constructed from the local activation times at each elec trode. During days 3 to 8 in culture, QRS amplitude and dV/dt(max) increase d with age. Concomitantly, with the culture maturation, QT interval (repres enting action potential duration) decreased, and T wave amplitude and slope s of the T wave ascending and descending limbs progressively increased. The changes in conduction velocity were different than those of the electrogra m properties, slightly increasing during the first 3 to 5 days and graduall y declining toward day 8 in culture. Conclusion: Establishment of uniform activation patterns in spontaneously f iring or driven myocytes in monolayer cultures is accompanied by organizati on 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 rel ations among gap junctions, conduction velocity, and propagation patterns, as well as a means to learn how gap junctional remodeling under pathophysio logic conditions predisposes the myocardium to arrhythmias.