Chloride Regulation: A Dynamic Equilibrium Crucial for Synaptic Inhibition

被引:172
作者
Doyon, Nicolas [1 ,2 ]
Vinay, Laurent [3 ,4 ]
Prescott, Steven A. [5 ,6 ]
De Koninck, Yves [1 ,7 ]
机构
[1] Inst Univ Sante Mentale Quebec, Quebec City, PQ G1J 2G3, Canada
[2] Univ Laval, Dept Math & Stat, Quebec City, PQ G1V 0A6, Canada
[3] CNRS, Inst Neurosci Timone, Team P3M, UMR 7289, F-13385 Marseille, France
[4] Aix Marseille Univ, F-13385 Marseille, France
[5] Hosp Sick Children, Program Neurosci & Mental Hlth, Toronto, ON M5G 1X8, Canada
[6] Univ Toronto, Dept Physiol, Toronto, ON M5S 1A8, Canada
[7] Univ Laval, Dept Psychiat & Neurosci, Quebec City, PQ G1V 0A6, Canada
基金
加拿大自然科学与工程研究理事会;
关键词
VENTRAL TEGMENTAL AREA; K-CL COTRANSPORTER; LAMINA-I NEURONS; IMPERMEANT ANIONS ESTABLISH; HIGH-CONDUCTANCE STATE; INTRACELLULAR CHLORIDE; PYRAMIDAL NEURONS; TRANSPORTER KCC2; DOWN-REGULATION; PATHOLOGICAL PAIN;
D O I
10.1016/j.neuron.2016.02.030
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Fast synaptic inhibition relies on tight regulation of intracellular Cl-. Chloride dysregulation is implicated in several neurological and psychiatric disorders. Beyond mere disinhibition, the consequences of Cl- dysregulation are multifaceted and best understood in terms of a dynamical system involving complex interactions between multiple processes operating on many spatiotemporal scales. This dynamical perspective helps explain many unintuitive manifestations of Cl- dysregulation. Here we discuss how taking into account dynamical regulation of intracellular Cl- is important for understanding how synaptic inhibition fails, how to best detect that failure, why Cl- regulation is energetically so expensive, and the overall consequences for therapeutics.
引用
收藏
页码:1157 / 1172
页数:16
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