Upregulation of expression of sarcoplasmic reticulum by TGF-beta 1 in cultured rat cardiac myocytes

Abstract

The effects of transforming growth factor-beta 1 (TGF-beta 1) on the function and structure of sarcoplasmic reticulum (SR) were studied in cultured 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 and frequency of Ca2+ oscillations in myocytes at day 2 of culture. Ryanodine did not affect the spontaneous contraction in nontreated and TGF-beta 1-treated myocytes. On the other hand, NE caused negative and positive chronotropic responses in nontreated and TGF-beta 1-treated cells, respectively. In the absence of extracellular Ca2+, ryanodine and NE did not affect the cytoplasmic Ca2+ concentration ([Ca2+]i) in the nontreated cells, whereas NE increased [Ca2+]i but ryanodine did not in the TGF-beta 1-treated cells. SR structures in TGF-beta 1-treated cells developed more than those in nontreated cells. The results indicate that TGF-beta 1 plays an important role in the upregulation of SR function and structure of cultured neonatal rat cardiac myocytes.