Basic fibroblast growth factor activates calcium channels in neonatal rat cardiomyocytes.
Basic fibroblast growth factor (bFGF) is a potent mitogen for many cell lineages including fetal cardiomyocytes. Furthermore, bFGF has been shown to modify gene expression, in vitro, in adult nonproliferative ventricular myocytes. This effect is suspected to be partly responsible for the genetic modifications that occur in vivo under pathophysiological conditions such as ischemia or pressure overload and that lead to myocardial hypertrophy. However, little is known about the first steps of the molecular mechanisms that take place soon after cell activation by bFGF. In this study, using biochemical and electrophysiological approaches, we have established, on cardiomyocytes cultured from neonatal rat ventricles, that (i) differentiated beating cells express at least two classes of bFGF-receptors having high and low affinity (Kd = 10 +/- 2 pM and 1 +/- 0.5 nM); (ii) the stimulation of these bFGF receptors promotes an increase in the beating frequencies of cultured cardiomyocytes (40 +/- 10%); (iii) bFGF provokes the activation of poorly specific and voltage-independent calcium channels (12pS); (iv) inositol 1,4,5-trisphosphate enhances similar bFGF-induced Ca2+ currents and is therefore suspected to be a second messenger triggering this activation. These results support the presence, in cultured cardiomyocytes, of new calcium channels whose activation after bFGF binding may be partly responsible for the cell response to this growth factor.
Merle
P L
PL
Centre de Physiologie et Physiophatologie Cellulaire, Université Joseph Fourier, Grenoble, France.
Feige
J J
JJ
Verdetti
J
J
D000818:Animals; D000831:Animals, Newborn; D001665:Binding Sites; D015220:Calcium Channels / Q000187:drug effects*; D002478:Cells, Cultured; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D015544:Inositol 1,4,5-Trisphosphate / Q000494:pharmacology; D009200:Myocardial Contraction / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D017468:Receptors, Fibroblast Growth Factor / Q000502:physiology
D015220:Calcium Channels; D017468:Receptors, Fibroblast Growth Factor; D016222:Fibroblast Growth Factor 2; D015544:Inositol 1,4,5-Trisphosphate