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Transforming Growth Factor-β1 Regulates the Expression of Ryanodine-Sensitive Ca2+ Oscillations in Cardiac Myocytes

https://doi.org/10.1006/bbrc.1994.2513Get rights and content

Abstract

Factors which regulate sarcoplasmic reticulum (SR) gene expression are largely unknown. We investigated whether Transforming Growth Factor-β1 (TGF-β1) plays a role in the maintenance of Ca2+ handling mechanisms in isolated neonatal rat cardiomyocytes. Myocytes cultured in the presence of serum were found to beat continuously and undergo spontaneous Ca2+ oscillations whereas in the absence of serum the cells lost the ability to undergo cyclical Ca2+ oscillations. The oscillations were restored when serum-free medium was supplemented with TGF-β1. Both caffeine-induced Ca2+ elevations and the inhibitory effect of ryanodine on spontaneous activity were also dependent on the continued presence of TGF-β1; in its absence these indices of SR function were severely compromised. TGF-β1 therefore appears to play a critical role in the maintenance of Ca2+ oscillations in the heart by regulating the expression of the ryanodine-sensitive Ca2+ release mechanism.

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