NEURONAL SURVIVAL AND CALCIUM INFLUX INDUCED BY BASIC FIBROBLAST-GROWTH-FACTOR IN CHICK CILIARY GANGLION NEURONS

Basic fibroblast growth factor (bFGF/FGF2) exhibits widespread biologi cal activities in the nervous system. However, little is known about t he cascade of intracellular events that links.the activation of its ty rosine kinase receptors to these effects. Here we report that, in cili ary ganglion neurons from chick embryo, this.trophic factor significan tly enhanced neuronal survival. The percentage of surviving neurons wa s reduced when intracellular calcium was chelated by adding a membrane -permeable BAPTA eater to the culture medium, while antagonists of L- and N-type voltage-dependent calcium channels were ineffective. The io nic signals in response to bFGF stimulation have been studied using cy tofluorimetric and patch-clamp techniques. In single-cell Fura-2 measu rements, bFGF elicited a long lasting rise of the cytosolic calcium co ncentration that was dependent on [Ca2+](o). in whole-cell experiments , we observed a reversible depolarization of the membrane resting pote ntial and an inward cationic current. Single channel experiments, perf ormed in the cell-attached configuration, provide evidence for the act ivation of two families of Ca2+-permeable cationic channels. Moreover, inositol 1,4,5-trisphosphate opens channels with similar properties, suggesting that this cytosolic messenger can be responsible far the ca lcium influx induced by bFGF.