Homeostatic effects of depolarization on Ca2+ influx, synaptic signaling, and survival.
Depolarization promotes neuronal survival through moderate increases in Ca(2+) 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 Ca(2+) current density in hippocampal and cerebellar granule neurons. Depolarization rearing depressed multiple classes of high-voltage activated Ca(2+) current. Consistent with the idea that these changes also affected synaptic Ca(2+) 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 Ca(2+) 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 Ca(2+) concentration. Thus, compared with cells reared on conventional trophic factors, depolarization evokes homeostatic changes in Ca(2+) influx and signaling that render neurons vulnerable to cell death on activity reduction.
Moulder
Krista L
KL
Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Cormier
Robert J
RJ
Shute
Amanda A
AA
Zorumski
Charles F
CF
Mennerick
Steven
S
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D018698:Glutamic Acid / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology; D006706:Homeostasis / Q000502:physiology*; D036881:Long-Term Synaptic Depression / Q000502:physiology; D009433:Neural Inhibition / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000494:pharmacology; D017729:Presynaptic Terminals / Q000378:metabolism; D051381:Rats; D013569:Synapses / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D011188:Potassium; D002118:Calcium