Transforming growth factor-beta 1 regulates the expression of ryanodine-sensitive Ca2+ oscillations in cardiac myocytes.
Factors which regulate sarcoplasmic reticulum (SR) gene expression are largely unknown. We investigated whether Transforming Growth Factor-beta 1 (TGF-beta 1) 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-beta 1. Both caffeine-induced Ca2+ elevations and the inhibitory effect of ryanodine on spontaneous activity were also dependent on the continued presence of TGF-beta 1; in its absence these indices of SR function were severely compromised. TGF-beta 1 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.
Baker Medical Research Institute and Alfred Hospital, Prahran, Victoria, Australia.
C B
CB
Neylon
S M
SM
Bryant
P J
PJ
Little
A
A
Bobik
D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D005260:Female; D006321:Heart / Q000187:drug effects; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D011921:Rats, Inbred WKY; D012433:Ryanodine / Q000494:pharmacology*; D016212:Transforming Growth Factor beta / Q000502:physiology*
D016212:Transforming Growth Factor beta; D012433:Ryanodine; D002118:Calcium