GABA is the most prevalent inhibitory transmitter in the adult brain where it reduces neuronal activity mainly by opening chloride channels and hyperpolarizing the membrane potential. Surprisingly, after some types of neuronal trauma, GABA exerts a different action, depolarizing the membrane potential, raising cytoplasmic calcium levels, and increasing neuronal activity. After trauma, GABA can generate cytoplasmic calcium rises even larger than those elicited by the excitatory transmitter glutamate. Large GABA-mediated increases in intracellular calcium could be toxic. Furthermore, if inhibitory neuronal circuits switched to excitatory actions, maladaptive signaling may be generated in affected pathways. These depolarizing actions of GABA after injury are similar to GABA's function in early neuronal development. Neuronal injury, thus, may generate a recapitulation of GABA's role in ontogeny. NEUROSCIENTIST 3:281–286, 1997
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