QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (76) Citing Articles via Google Scholar Google Scholar Articles by Hegarty, J. L. Articles by Green, S. H. Search for Related Content PubMed PubMed Citation Articles by Hegarty, J. L. Articles by Green, S. H.

 Previous Article  |  Next Article 

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

This article has been cited by other articles:

				D. Greenwood, D. J. Jagger, L.-C. Huang, N. Hoya, P. R. Thorne, S. S. Wildman, B. F. King, K. Pak, A. F. Ryan, and G. D. Housley P2X receptor signaling inhibits BDNF-mediated spiral ganglion neuron development in the neonatal rat cochlea Development, April 1, 2007; 134(7): 1407 - 1417. [Abstract] [Full Text] [PDF]

				F. Lallemend, S. Hadjab, G. Hans, G. Moonen, P. P. Lefebvre, and B. Malgrange Activation of protein kinase C{beta}I constitutes a new neurotrophic pathway for deafferented spiral ganglion neurons J. Cell Sci., October 1, 2005; 118(19): 4511 - 4525. [Abstract] [Full Text] [PDF]

				B. Salthun-Lassalle, E. C. Hirsch, J. Wolfart, M. Ruberg, and P. P. Michel Rescue of Mesencephalic Dopaminergic Neurons in Culture by Low-Level Stimulation of Voltage-Gated Sodium Channels J. Neurosci., June 30, 2004; 24(26): 5922 - 5930. [Abstract] [Full Text] [PDF]

				T. Schimmang, J. Tan, M. Muller, U. Zimmermann, K. Rohbock, I. Kopschall, A. Limberger, L. Minichiello, and M. Knipper Lack of Bdnf and TrkB signalling in the postnatal cochlea leads to a spatial reshaping of innervation along the tonotopic axis and hearing loss Development, October 1, 2003; 130(19): 4741 - 4750. [Abstract] [Full Text] [PDF]

				J. Bok, X.-M. Zha, Y.-S. Cho, and S. H. Green An Extranuclear Locus of cAMP-Dependent Protein Kinase Action Is Necessary and Sufficient for Promotion of Spiral Ganglion Neuronal Survival by cAMP J. Neurosci., February 1, 2003; 23(3): 777 - 787. [Abstract] [Full Text] [PDF]

				T. Shinohara, G. Bredberg, M. Ulfendahl, I. Pyykko, N. P. Olivius, R. Kaksonen, B. Lindstrom, R. Altschuler, and J. M. Miller Neurotrophic factor intervention restores auditory function in deafened animals PNAS, January 24, 2002; (2002) 32677999. [Abstract] [Full Text] [PDF]

				M. R. Hansen, X.-M. Zha, J. Bok, and S. H. Green Multiple Distinct Signal Pathways, Including an Autocrine Neurotrophic Mechanism, Contribute to the Survival-Promoting Effect of Depolarization on Spiral Ganglion Neurons In Vitro J. Neurosci., April 1, 2001; 21(7): 2256 - 2267. [Abstract] [Full Text] [PDF]

				M. Hetman, K. Kanning, J. E. Cavanaugh, and Z. Xia Neuroprotection by Brain-derived Neurotrophic Factor Is Mediated by Extracellular Signal-regulated Kinase and Phosphatidylinositol 3-Kinase J. Biol. Chem., August 6, 1999; 274(32): 22569 - 22580. [Abstract] [Full Text] [PDF]

				A. G. Estevez, N. Spear, J. A. Thompson, T. L. Cornwell, R. Radi, L. Barbeito, and J. S. Beckman Nitric Oxide-Dependent Production of cGMP Supports the Survival of Rat Embryonic Motor Neurons Cultured with Brain-Derived Neurotrophic Factor J. Neurosci., May 15, 1998; 18(10): 3708 - 3714. [Abstract] [Full Text] [PDF]

				T. Shinohara, G. Bredberg, M. Ulfendahl, I. Pyykko, N. P. Olivius, R. Kaksonen, B. Lindstrom, R. Altschuler, and J. M. Miller Neurotrophic factor intervention restores auditory function in deafened animals PNAS, February 5, 2002; 99(3): 1657 - 1660. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help