Excitatory actions of GABA after neuronal trauma

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

Research output: Contribution to journalArticlepeer-review

202 Scopus citations


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
Issue number13
StatePublished - 1996

All Science Journal Classification (ASJC) codes

  • General Neuroscience


Dive into the research topics of 'Excitatory actions of GABA after neuronal trauma'. Together they form a unique fingerprint.

Cite this