TROPHIC SUPPORT OF CULTURED SPIRAL GANGLION NEURONS BY DEPOLARIZATIONEXCEEDS AND IS ADDITIVE WITH THAT BY NEUROTROPHINS OR CAMP AND REQUIRES ELEVATION OF [CA2+](I) WITHIN A SET RANGE

Spiral ganglion neurons (SGNs) require both pre- and postsynaptic cont acts to maintain viability. BDNF, NT-3, chlorphenylthio-cAMP, and depo larization (veratridine or elevated [K+](o)) all promote survival of S GNs in vitro, depolarization being the most effective. Combining diffe rent trophic stimuli increases survival in an additive manner. Neurotr ophins and depolarization maintain comparable soma size and neurite ex tension, but SGNs are shrunken in cAMP. Elevated [K+](o) has a biphasi c effect on SGN survival; survival improves as [K+](o) is raised to 30 mM (30K) and falls as [K+](o) is further increased; SGN survival in 8 0 mM [K+](o) (80K) is poor relative to survival in 30K. These response s to elevated [K+](o) are potentiated by an L-type channel agonist, wh ereas L-type Ca2+ channel blockers antagonize the trophic effect of de polarization. Four hours after depolarization, steady-state [Ca2+](i) is elevated in SGNs in 30K and further elevated in SGNs in 80K. At 22 hr after depolarization, by which time death of neurons in 80K has beg un, elevated [Ca2+](i) levels in surviving neurons in 80K are not high er than those in neurons in 30K (similar to 150-450 nM), suggesting th at neurons with high [Ca2+](i) are preferentially lost. Veratridine ca uses oscillatory increases in [Ca2+](i) to 250-350 nM. Thus, [Ca2+](i) is predictive of cell survival; [Ca2+](i) elevated to 100-500 nM in a sustained or oscillatory manner permits SGN survival independent of e xogenous neurotrophic factors. Higher [Ca2+](i) is associated with cel l death.