Ionic plasticity of GABA signaling relies on short-term and long term changes in EGABA.
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Cl− transport and carboanhydrases play a key role in ionic plasticity and epilepsy.
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GABAergic transmission has both seizure-suppressing and seizure-promoting effects.
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TrkB and calpain act on GABA signaling to coordinate the process of epileptogenesis.
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GABA signaling has context-specific and age-specific effects in health and disease.
Concepts of epilepsy, based on a simple change in neuronal excitation/inhibition balance, have subsided in face of recent insights into the large diversity and context-dependence of signaling mechanisms at the molecular, cellular and neuronal network level. GABAergic transmission exerts both seizure-suppressing and seizure-promoting actions. These two roles are prone to short-term and long-term alterations, evident both during epileptogenesis and during individual epileptiform events. The driving force of GABAergic currents is controlled by ion-regulatory molecules such as the neuronal K-Cl cotransporter KCC2 and cytosolic carbonic anhydrases. Accumulating evidence suggests that neuronal ion regulation is highly plastic, thereby contributing to the multiple roles ascribed to GABAergic signaling during epileptogenesis and epilepsy.