UP-REGULATION OF EXPRESSION OF SARCOPLASMIC-RETICULUM BY TGF-BETA-1 IN CULTURED RAT CARDIAC MYOCYTES

The effects of transforming growth factor-beta 1 (TGF-beta 1) on the f unction and structure of sarcoplasmic reticulum (SR) were studied in c ultured neonatal rat cardiac myocytes. The cardiac myocytes at days 2 and 6 of culture exhibited spontaneous contraction; however, the rate of contraction increased and became regular, depending on culture day. Ryanodine and norepinephrine (NE) increased the rate of contraction a nd frequency of Ca2+ oscillations in myocytes at day 2 of culture. Rya nodine did not affect the spontaneous contraction in nontreated and TG F-beta 1-treated myocytes. On the other hand, NE caused negative and p ositive chronotropic responses in nontreated and TGF-beta 1-treated ce lls, respectively. In the absence of extracellular Ca2+, ryanodine and NE did not affect the cytoplasmic Ca2+ concentration ([Ca2+](i)) in t he nontreated cells, whereas NE increased [Ca2+](i) but ryanodine did not in the TGF-beta 1-treated cells. SR structures in TGF-beta 1-treat ed cells developed more than those in nontreated cells. The results in dicate that TGF-beta 1 plays an important role in the upregulation of SR function and structure of cultured neonatal rat cardiac myocytes.