Excitatory actions of GABA after neuronal trauma

Anthony N. Van den Pol, Karl Obrietan, Gong Chen

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Abstract

GABA is the dominant inhibitory neurotransmitter in the CNS. By opening Cl- channels, GABA generally hyperpolarizes the membrane potential, decreases neuronal activity, and reduces intracellular Ca2+ of mature neurons. In the present experiment, we show that after neuronal trauma, GABA, both synaptically released and exogenously applied, exerted a novel and opposite effect, depolarizing neurons and increasing intracellular Ca2+. Different types of trauma that were effective included neurite transection, replating, osmotic imbalance, and excess heat. The depolarizing actions of GABA after trauma increased Ca2+ levels up to fourfold in some neurons, occurred in more than half of the severely injured neurons, and was long lasting (>1 week). The mechanism for the reversed action of GABA appears to be a depolarized Cl- reversal potential that results in outward rather than inward movement of Cl-, as revealed by gramicidin-perforated whole-cell patch-clamp recording. The consequent depolarization and resultant activation of the nimodipine sensitive L- and conotoxin-sensitive N-type voltage- activated Ca2+ channel allows extracellular Ca2+ to enter the neuron. The long-lasting capacity to raise Ca2+ may give GABA a greater role during recovery from trauma in modulating gene expression, and directing and enhancing outgrowth of regenerating neurites. On the negative side, by its depolarizing actions, GABA could increase neuronal damage by raising cytosolic Ca2+ levels in injured cells. Furthermore, the excitatory actions of GABA after neuronal injury may contribute to maladaptive signal transmission in affected GABAergic brain circuits.

Original languageEnglish (US)
Pages (from-to)4283-4292
Number of pages10
JournalJournal of Neuroscience
Volume16
Issue number13
Publication statusPublished - Jul 3 1996

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All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

Cite this

Van den Pol, A. N., Obrietan, K., & Chen, G. (1996). Excitatory actions of GABA after neuronal trauma. Journal of Neuroscience, 16(13), 4283-4292.