Transient elevations in intracellular calcium are sufficient to induce sustained responsiveness to the neurotrophic...

The present study investigates how a neuron's past history of neural activity may alter its responsiveness to subsequent signals. We demonstrate that a depolarizing pulse of extracellular potassium can prime neurons to become responsive to basic fibroblast growth factor (bFGF), even when the pulse is brief and occurs prior to addition of bFGF. Specifically, we subjected cultured embryonic chick ciliary ganglion neurons (E7) to a short pulse of elevated extracellular potassium followed by addition of bFGF and tested the effect of such treatment on neuronal survival. Neurons treated in this manner produced high levels of survival, whereas neurons exposed to either the pulse alone or the continuous presence of bFGF alone failed to promote any significant levels of survival. This priming effect of depolarization on bFGF-induced survival was blocked by calcium channel antagonists. To test the time dependency of this effect, we increased the time interval between termination of the calcium pulse and addition of bFGF. Our results demonstrate that a brief elevation in intracellular calcium has long lasting effects, up to 8 h after cessation of the depolarizing pulse, on neuronal responsiveness to bFGF. These findings suggest how a developing neuron's history of activity can alter its subsequent ability to respond to neurotrophic factors and has significant implications on the mechanisms by which activity may influence neuronal survival.