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The Journal of Neuroscience, March 1, 2003, 23(5):1825

Homeostatic Effects of Depolarization on Ca²⁺ Influx, Synaptic Signaling, and Survival

Krista L. Moulder, Robert J. Cormier, Amanda A. Shute, Charles F. Zorumski, and Steven Mennerick

Departments of Psychiatry and Neurobiology, Washington University School of Medicine, St. Louis, Missouri 63110

Depolarization promotes neuronal survival through moderate increases in Ca²⁺ influx, but the effects of survival-promoting depolarization (vs conventional trophic support) on neuronal signaling are poorly characterized. We found that chronic, survival-promoting depolarization, but not conventional trophic support, selectively decreased the somatic Ca²⁺ current density in hippocampal and cerebellar granule neurons. Depolarization rearing depressed multiple classes of high-voltage activated Ca²⁺ current. Consistent with the idea that these changes also affected synaptic Ca²⁺ channels, chronic depolarization presynaptically depressed hippocampal neurotransmission. Six days of depolarization rearing completely abolished glutamate transmission but altered GABA transmission in a manner consistent with the alterations of Ca²⁺ current. The continued survival of depolarization-reared neurons was extremely sensitive to the re-establishment of basal culture conditions and was correlated with the effects on intracellular Ca²⁺ concentration. Thus, compared with cells reared on conventional trophic factors, depolarization evokes homeostatic changes in Ca²⁺ influx and signaling that render neurons vulnerable to cell death on activity reduction.

Key words: depolarization; HVA Ca²⁺ current; glutamate; GABA; synaptic depression; neuronal survival

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Copyright © 2003 Society for Neuroscience  0270-6474/03/2351825-07$05.00/0

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