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Volume 17, Number 6, Issue of March 15, 1997 pp. 1959-1970
Copyright ©1997 Society for Neuroscience

Trophic Support of Cultured Spiral Ganglion Neurons by Depolarization Exceeds and Is Additive with that by Neurotrophins or cAMP and Requires Elevation of [Ca²⁺]_i within a Set Range

Received Sept. 5, 1996; revised Jan. 7, 1997; accepted Jan. 13, 1997.

Joseph L. Hegarty^{1, 2}, Alan R. Kay¹, and Steven H. Green^{1, 2}

Departments of ¹ Biological Sciences and ² Otolaryngology, University of Iowa, Iowa City, Iowa 52242

Spiral ganglion neurons (SGNs) require both pre- and postsynaptic contacts to maintain viability. BDNF, NT-3, chlorphenylthio-cAMP, and depolarization (veratridine or elevated [K⁺]_o) all promote survival of SGNs in vitro, depolarization being the most effective. Combining different trophic stimuli increases survival in an additive manner. Neurotrophins and depolarization maintain comparable soma size and neurite extension, but SGNs are shrunken in cAMP. Elevated [K⁺]_o has a biphasic 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 80 mM [K⁺]_o (80K) is poor relative to survival in 30K. These responses to elevated [K⁺]_o are potentiated by an L-type channel agonist, whereas L-type Ca²⁺ channel blockers antagonize the trophic effect of depolarization. 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 begun, elevated [Ca²⁺]_i levels in surviving neurons in 80K are not higher than those in neurons in 30K (~150-450 nM), suggesting that neurons with high [Ca²⁺]_i are preferentially lost. Veratridine causes 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 exogenous neurotrophic factors. Higher [Ca²⁺]_i is associated with cell death.

Key words: depolarization; calcium; neurotrophic factor; neurotrophin; spiral ganglion neuron; cell survival

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