Altered chloride homeostasis in neurological disorders: a new target

被引：135

作者：

De Koninck, Yves ^{[1
]}

机构：

[1] Univ Laval, Ctr Rech Robert Giffard, Unite Neurobiol Cellulaire, Quebec City, PQ G1J 2G3, Canada

来源：

CURRENT OPINION IN PHARMACOLOGY | 2007年 / 7卷 / 01期

基金：

加拿大自然科学与工程研究理事会; 加拿大健康研究院;

关键词：

D O I：

10.1016/j.coph.2006.11.005

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Other than modifying either neurotransmitter release or receptor expression and/or properties, one way to modulate gamma-aminobutyric acid (GABA)(A) and glycine receptor-mediated signalling is to alter the transmembrane gradient for chloride ions. Because intracellular chloride concentration is low in neurons, and the reversal potential for chloride currents is close to the resting membrane potential, small changes in intracellular chloride concentration can dramatically affect the strength and even polarity of GABA/glycine-mediated transmission. It now appears that chloride homeostasis is actively regulated in the adult brain and affected by endogenous neuromodulators such as brain-derived neurotrophic factor. Modulating chloride gradients even emerges as a mechanism by which microglia can control neuronal excitability. These findings, together with the observation of altered chloride homeostasis in several neurological disorders, point to new targets for therapeutic agents.

引用

收藏

页码：93 / 99

页数：7

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