Differential response of cultured adult cardiac muscle cells to a tumor promotor: analysis of myofibrillar organization.
Cultured adult rat ventricular cardiac muscle cells were exposed to varying concentrations of 12-0-tetradecanoyl-phorbol-13 acetate (TPA) for two weeks. A considerable number of cardiac myocytes exposed to a medium with less than 200 ng/ml TPA were rich in myofibrils. The rest of the myocytes lacked organized myofibrils; the terminal parts of these myofibrils were transformed into cord-like structures largely consisting of dense Z-band materials. Some of these aberrant myofibrils contained short normal myofibrillar segments, with sarcomeres. A number of myocytes exposed to 200-250 ng/ml TPA contained myofibrils, which terminated in cord-like structures. The Z-band materials appeared as amorphous dense matrices and some sarcomeres were replaced completely or partially by leptomeres; the myocytes contained autophagosomes. The other myocytes did not contain myofibrils when exposed to the above higher concentrations of TPA. The patches of Z-band materials and structures containing Z-band materials attached to thin filaments on either side were scattered throughout the sarcoplasm of the cells, which were packed with myofilaments and 10 nm microfilaments. Some of these myocytes assumed a spindle shape and contained myofilaments, 10 nm microfilaments and leptomeres. Some of the myocytes, treated with TPA for 1-7 days and then allowed to recover in control medium for 7 days, contained various stages of myofibrillar organization, which did not differ significantly from those of the myofibril-containing cells exposed continuously to TPA as discussed above. The rest of the myocytes during the recovery period in control medium did not contain myofibrils. Rough endoplasmic reticulum and Golgi bodies in TPA-treated myocytes were found to be highly developed as compared to the controls. It is evident from these studies that the responsiveness of cardiac myocytes to TPA not only differs from that of skeletal muscle cells studied by others, but also varies within a population of cardiac myocytes.