Intracellular calcium regulates the survival of early sensory neurons before they become dependent on neurotrophic factors.

To investigate the role of intracellular Ca2+ in the survival of developing neurons before they become neurotrophic factor dependent, we have studied chick embryo nodose neurons, which have a particularly protracted period of neuorophic factor independence. Pharmacological reduction of intracellular free Ca2+ or depletion of either Ca(2+)-regulated or inositol trisphosphate-regulated intracellular Ca2+ stores kills early neurotrophic factor-independent neurons, but has a negligible effect on older neurons growing in the presence of brain-derived neutrotrophic factor. Shortly before they become dependent on brain-derived neurotrophic factor, nodose neurons express L-type Ca2+ channels and their survival can be enhanced by depolarization-induced Ca2+ influx. We conclude that intracellular Ca2+ plays a role in regulating neuronal survival both prior to and after the onset of neurotrophic factor dependence, but does not mediate the survival-promoting effects of neurotrophic factors.