Excitatory Actions of GABA after Neuronal Trauma
Journal of Neuroscience
GABA is the dominant inhibitory neurotransmitter in the CNS. By opening Cl Ϫ channels, GABA generally hyperpolarizes the membrane potential, decreases neuronal activity, and reduces intracellular Ca 2ϩ 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 Ca 2ϩ . Different types of trauma that were effective included neurite
... ve included neurite transection, replating, osmotic imbalance, and excess heat. The depolarizing actions of GABA after trauma increased Ca 2ϩ levels up to fourfold in some neurons, occurred in more than half of the severely injured neurons, and was long lasting (Ͼ1 week). The mechanism for the reversed action of GABA appears to be a depolarized Cl Ϫ reversal potential that results in outward rather than inward movement of Cl Ϫ , 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 Ca 2ϩ channel allows extracellular Ca 2ϩ to enter the neuron. The long-lasting capacity to raise Ca 2ϩ 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 Ca 2ϩ levels in injured cells. Furthermore, the excitatory actions of GABA after neuronal injury may contribute to maladaptive signal transmission in affected GABAergic brain circuits.