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Neurotrophic Signaling by Membrane Electrical Activity in Spiral Ganglion Neurons

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Cell and Molecular Biology of the Ear

Abstract

Survival of spiral ganglion neurons (SGNs) in vitro is supported by neurotrophins (BDNF and NT-3), by permeant cyclic AMP analogs, and by depolarization; the latter being most efficacious. These stimuli act through independent intracellular signal pathways, which accounts for their additivity and for their different effects on neuronal morphology and neurite growth. Depolarization promotes survival by raising cytosolic Ca2+ concentration within a set range. Endogenous cyclic AMP signaling and an autocrine neurotrophin mechanism contribute significantly to the survival-promoting effect of depolarization. However, the major intracellular signals recruited by Ca2+ to promote survival are the Ca2+/CaM-dependent protein kinases (CaMKs). CaMKs are activated by depolarization in SGNs. CaMK inhibitors inhibit survival-promoting effects of depolarization. Transfection of constitutively active CaMKII and CaMKIV mutants into SGNs permits survival even in the absence of exogenous survival-promoting stimuli. CaMKII and CaMKIV activity are not additive in their promotion of survival, indicating that they act via the same downstream effector(s). However, CaMKII and CaMKIV differ dramatically in their other effects on SGNs: CaMKII activity strongly inhibits neurite outgrowth but CaMKIV activity has no such effect. These observations of the ability of SGNs to sum independent intracellular signals to promote survival helps in understanding how SGN survival is supported in vivo and establishes SGNs as a model for studying the molecular mechanism of summation. These observations also have clinical implications with regard to means used to support SGN survival in deaf people.

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  1. Departments of Biological Sciences and Otolaryngology, University of Iowa, Iowa City, IA

    Steven H. Green

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  1. Steven H. Green
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  1. House Ear Institute, Los Angeles, California, USA

    David J. Lim

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© 2000 Kluwer Academic/Plenum Publishers, New York

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Green, S.H. (2000). Neurotrophic Signaling by Membrane Electrical Activity in Spiral Ganglion Neurons. In: Lim, D.J. (eds) Cell and Molecular Biology of the Ear. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-4223-0_13

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  • DOI: https://doi.org/10.1007/978-1-4615-4223-0_13

  • Publisher Name: Springer, Boston, MA

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