BASIC FIBROBLAST GROWTH-FACTOR ACTIVATES CALCIUM CHANNELS IN NEONATALRAT CARDIOMYOCYTES

Basic fibroblast growth factor (bFGF) is a potent mitogen for many cel l lineages including fetal cardiomyocytes. Furthermore, bFGF has been shown to modify gene expression, in vitro, in adult nonproliferative v entricular myocytes. This effect is suspected to be partly responsible for the genetic modifications that occur in vivo under pathophysiolog ical conditions such as ischemia or pressure overload and that lead to myocardial hypertrophy. However, little is known about the first step s of the molecular mechanisms that take place soon after cell activati on by bFGF. In this study, using bio chemical and electrophysiological approaches, we have established, on cardiomyocytes cultured from neon atal rat ventricles, that (i) differentiated beating cells express at least two classes of bFGF-receptors having high and low affinity (K-d = 10 +/- 2 pM and 1 +/- 0.5 nM); (ii) the stimulation of these bFGF re ceptors promotes an increase in the beating frequencies of cultured ca rdiomyocytes (40 +/- 10%); (iii) bFGF provokes the activation of poorl y specific and voltage-independent calcium channels (12pS); (iv) inosi tol 1,4,5-trisphosphate enhances similar bFGF-induced Ca2+ currents an d is therefore suspected to be a second messenger triggering this acti vation. These results support the presence, in cultured cardiomyocytes , of new calcium channels whose activation after bFGF binding may be p artly responsible for the cell response to this growth factor.