The GABA Excitatory/Inhibitory Shift in Brain Maturation and Neurological Disorders

被引:441
作者
Ben-Ari, Yehezkel [1 ,2 ]
Khalilov, Ilgam [1 ,2 ]
Kahle, Kristopher T. [3 ,4 ]
Cherubini, Enrico [5 ]
机构
[1] INSERM, INMED, U901, F-13258 Marseille, France
[2] Neurochlore, Marseille, France
[3] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA
[4] Harvard Univ, Sch Med, Boston, MA USA
[5] Int Sch Adv Studies SISSA, Trieste, Italy
基金
英国医学研究理事会;
关键词
GABA; excitation/inhibition; neonatal neurons; epilepsies; bumetanide; NKCC1; KCC2; phenobarbital; diazepam; GABA-acting antiepileptic drugs; GIANT DEPOLARIZING POTENTIALS; LONG-TERM POTENTIATION; NEURONAL CHLORIDE ACCUMULATION; DEVELOPING RAT HIPPOCAMPUS; NETWORK ACTIVITY; DEVELOPING NEOCORTEX; EXCITATORY ACTIONS; POSTSYNAPTIC ACTIVITY; COTRANSPORTER KCC2; NEONATAL SEIZURES;
D O I
10.1177/1073858412438697
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Ionic currents and the network-driven patterns they generate differ in immature and adult neurons: The developing brain is not a "small adult brain." One of the most investigated examples is the developmentally regulated shift of actions of the transmitter GABA that inhibit adult neurons but excite immature ones because of an initially higher intracellular chloride concentration [Cl-](i), leading to depolarizing and often excitatory actions of GABA instead of hyperpolarizing and inhibitory actions. The levels of [Cl-](i) are also highly labile, being readily altered transiently or persistently by enhanced episodes of activity in relation to synaptic plasticity or a variety of pathological conditions, including seizures and brain insults. Among the plethora of channels, transporters, and other devices involved in controlling [Cl-](i), two have emerged as playing a particularly important role: the chloride importer NKCC1 and the chloride exporter KCC2. Here, the authors stress the importance of determining how [Cl-](i) is dynamically regulated and how this affects brain operation in health and disease. In a clinical perspective, agents that control [Cl-](i) and reinstate inhibitory actions of GABA open novel therapeutic perspectives in many neurological disorders, including infantile epilepsies, autism spectrum disorders, and other developmental disorders.
引用
收藏
页码:467 / 486
页数:20
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