ADULT-RAT CARDIOMYOCYTES IN CULTURE - A MODEL SYSTEM TO STUDY THE PLASTICITY OF THE DIFFERENTIATED CARDIAC PHENOTYPE AT THE MOLECULAR AND CELLULAR-LEVELS

Adult rat cardiomyocytes (ARCs) in long-term culture, which show a dis tinct adaptive flexibility, are presented as a system to study cardiac cell hypertrophy in vitro. In the first 1-2 weeks after isolation, AR Cs undergo a process of de- and redifferentiation during which the cel l morphology is remodeled and the myofibrillar apparatus is restructur ed, accompanied by a cell enlargement. The growing cells spread and ev entually establish new cell-cell contacts, which display newly formed intercalated discs; synchronous cell beating is resumed in the resulti ng tissuelike sheet. During myofibrillogenesis, the early fetal progra m of gene expression is reactivated for several genes, as is observed during hemodynamic overload hypertrophy. The cells resume hormonal act ivity and express atrial natriuretic factor (ANF); the expression patt ern of ANF is also reminiscent of that seen in hypertrophy. In cells g rown in a medium conditioned by 12-day ARCs, though, myofibrillogenesi s is accelerated and accompanied by a downregulation of ANF. In a crea tine-deficient medium, on the other hand, the ARCs display giant mitoc hondria with paracrystalline inclusions imitating a situation found, f or example, in mitochondrial myopathies.