Excitatory Actions of GABA after Neuronal Trauma
TLDR
After neuronal trauma, GABA exerted a novel and opposite effect, depolarizing neurons and increasing intracellular Ca2+.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 Ca 2+ 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 2+ . Different types of trauma that were effective included neurite transection, replating, osmotic imbalance, and excess heat. The depolarizing actions of GABA after trauma increased Ca 2+ 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 Ca 2+ channel allows extracellular Ca 2+ to enter the neuron. The long-lasting capacity to raise Ca 2+ 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 2+ levels in injured cells. Furthermore, the excitatory actions of GABA after neuronal injury may contribute to maladaptive signal transmission in affected GABAergic brain circuits.read more
Citations
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The K+/Cl- co-transporter KCC2 renders GABA hyperpolarizing during neuronal maturation.
Claudio Rivera,Juha Voipio,John A. Payne,Eva Ruusuvuori,Hannele Lahtinen,Karri Lamsa,Ulla Pirvola,Mart Saarma,Kai Kaila +8 more
TL;DR: It is shown that, in pyramidal neurons of the rat hippocampus, the ontogenetic change in GABAA-mediated responses from depolarizing to hyperpolarizing is coupled to a developmental induction of the expression of the neuronal Cl−-extruding K+/Cl − co-transporter, KCC2 (ref. 7).
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Trans-synaptic shift in anion gradient in spinal lamina I neurons as a mechanism of neuropathic pain
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TL;DR: Evidence is presented for a novel mechanism of disinhibition following peripheral nerve injury that involves a trans-synaptic reduction in the expression of the potassium–chloride exporter KCC2, and the consequent disruption of anion homeostasis in neurons of lamina I of the superficial dorsal horn, one of the main spinal nociceptive output pathways.
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Cation–chloride co-transporters in neuronal communication, development and trauma
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