Double-edged GABAergic synaptic transmission in seizures: The importance of chloride plasticity

被引：36

作者：

Wang, Ying ^{[1
]}

Wang, Yi ^{[1
]}

Chen, Zhong ^{[1
,2
]}

机构：

[1] Zhejiang Univ, Inst Pharmacol & Toxicol, Key Lab Med Neurobiol, Minist Hlth China,Coll Pharmaceut Sci, Hangzhou, Zhejiang, Peoples R China

[2] Zhejiang Univ, Sch Med, Epilepsy Ctr, Affiliated Hosp 2, Hangzhou, Zhejiang, Peoples R China

来源：

BRAIN RESEARCH | 2018年 / 1701卷

基金：

中国国家自然科学基金;

关键词：

Epilepsy; GABA receptor; Chloride plasticity; Cation-chloride cotransporter; CL-COTRANSPORTER KCC2; TEMPORAL-LOBE EPILEPSY; SUBUNIT MESSENGER-RNAS; ENHANCES PHENOBARBITAL EFFICACY; GABA(A) RECEPTOR FUNCTION; RAT-BRAIN; EPILEPTIFORM DISCHARGES; DIFFERENTIAL EXPRESSION; ALTERED EXPRESSION; SURFACE EXPRESSION;

D O I：

10.1016/j.brainres.2018.09.008

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

GABAergic synaptic inhibition, which is a critical regulator of neuronal excitability, is closely involved in epilepsy. Interestingly, fast GABAergic transmission mediated by Cl- permeable GABAA receptors can bi-directionally exert both seizure-suppressing and seizure-promoting actions. Accumulating evidence suggests that chloride plasticity, the driving force of GABAA receptor-mediated synaptic transmission, contributes to the double-edged role of GABAergic synapses in seizures. Large amounts of Cl- influx can overwhelm Cl- extrusion during seizures not only in healthy tissue in a short-term "activity-dependent" manner, but also in chronic epilepsy in a long-term, irreversible "pathology-dependent" manner related to the dysfunction of two chloride transporters: the chloride importer NKCC1 and the chloride exporter KCC2. In this review, we address the importance of chloride plasticity for the "activity-dependent" and "pathology-dependent" mechanisms underlying epileptic events and provide possible directions for further research, which may be clinically important for the design of GABAergic synapse-targeted precise therapeutic interventions for epilepsy.

引用

页码：126 / 136

页数：11

共 162 条

[1] The Contribution of Raised Intraneuronal Chloride to Epileptic Network Activity [J].

Alfonsa, Hannah ;

Merricks, Edward M. ;

Codadu, Neela K. ;

Cunningham, Mark O. ;

Deisseroth, Karl ;

Racca, Claudia ;

Trevelyan, Andrew J. .

JOURNAL OF NEUROSCIENCE, 2015, 35 (20) :7715-7726

[2] INTRACELLULAR CHLORIDE REGULATION IN AMPHIBIAN DORSAL-ROOT GANGLION NEURONS STUDIED WITH ION-SELECTIVE MICROELECTRODES [J].

ALVAREZLEEFMANS, FJ ;

GAMINO, SM ;

GIRALDEZ, F ;

NOGUERON, I .

JOURNAL OF PHYSIOLOGY-LONDON, 1988, 406 :225-246

[3]

[Anonymous], 2012, JASPERS BASIC MECH E

[4] Differential expression patterns of chloride transporters, Na+-K+-2Cl--cotransporter and K+-Cl--cotransporter, in epilepsy-associated malformations of cortical development [J].

Aronica, E. ;

Boer, K. ;

Redeker, S. ;

Spliet, W. G. M. ;

Van Rijen, P. C. ;

Troost, D. ;

Gorter, J. A. .

NEUROSCIENCE, 2007, 145 (01) :185-196

[5] The antiepileptic and ictogenic effects of optogenetic neurostimulation of PV-expressing interneurons [J].

Assaf, Fadi ;

Schiller, Yitzhak .

JOURNAL OF NEUROPHYSIOLOGY, 2016, 116 (04) :1694-1704

[6]

Avoli M, 1996, J NEUROSCI, V16, P3912

[7] GABAergic synchronization in the limbic system and its role in the generation of epileptiform activity [J].

Avoli, Massimo ;

de Curtis, Marco .

PROGRESS IN NEUROBIOLOGY, 2011, 95 (02) :104-132

[8] Reducing premature KCC2 expression rescues seizure susceptibility and spine morphology in atypical febrile seizures [J].

Awad, Patricia N. ;

Sanon, Nathalie T. ;

Chattopadhyaya, Bidisha ;

Carrico, Josianne Nunes ;

Ouardouz, Mohamed ;

Gagne, Jonathan ;

Duss, Sandra ;

Wolf, Daniele ;

Desgent, Sebastien ;

Cancedda, Laura ;

Carmant, Lionel ;

Di Cristo, Graziella .

NEUROBIOLOGY OF DISEASE, 2016, 91 :10-20

[9]

AWAPARA J, 1950, J BIOL CHEM, V187, P35

[10] Positive shifts of the GABAA receptor reversal potential due to altered chloride homeostasis is widespread after status epilepticus [J].

Barmashenko, Gleb ;

Hefft, Stefan ;

Aertsen, Ad ;

Kirschstein, Timo ;

Koehling, Ruediger .

EPILEPSIA, 2011, 52 (09) :1570-1578

← 1 2 3 4 5 6 7 8 9 10 →