The K(+)-Cl(-) Cotransporter KCC2 and Chloride Homeostasis: Potential Therapeutic Target in Acute Central Nervous System Injury.
The K(+)-Cl(-) cotransporter-2 (KCC2) is a well-known member of the electroneutral cation-chloride cotransporters with a restricted expression pattern to neurons. This transmembrane protein mediates the efflux of Cl(-) out of neurons and exerts a critical role in inhibitory γ-aminobutyric acidergic (GABAergic) and glycinergic neurotransmission. Moreover, KCC2 participates in the regulation of various physiological processes of neurons, including cell migration, dendritic outgrowth, spine morphology, and dendritic synaptogenesis. It is important to note that down-regulation of KCC2 is associated with the pathogenesis of multiple neurological diseases, which is of particular relevance to acute central nervous system (CNS) injury. In this review, we aim to survey the pathogenic significance of KCC2 down-regulation under the condition of acute CNS injuries. We propose that further elucidation of the molecular mechanisms regarding KCC2 down-regulation after acute CNS injuries is necessary because of potential promising avenues for prevention and treatment of acute CNS injury.
Department of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, 88 Jiefang Road, Hangzhou, 310009, Zhejiang, China.
Haijian
H
Wu
Department of Cardiology, Zhejiang Provincial People's Hospital, Hangzhou, China.
Xiaoru
X
Che
Department of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, 88 Jiefang Road, Hangzhou, 310009, Zhejiang, China.
Junjia
J
Tang
Department of Emergency Medicine, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Feiqiang
F
Ma
Department of Neurosurgery, New York-Presbyterian Hospital, New York, NY, USA.
Kun
K
Pan
Department of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, 88 Jiefang Road, Hangzhou, 310009, Zhejiang, China.
Mingfei
M
Zhao
Department of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, 88 Jiefang Road, Hangzhou, 310009, Zhejiang, China.
Anwen
A
Shao
Department of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, 88 Jiefang Road, Hangzhou, 310009, Zhejiang, China.
Qun
Q
Wu
Department of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, 88 Jiefang Road, Hangzhou, 310009, Zhejiang, China.
Jianmin
J
Zhang
Department of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, 88 Jiefang Road, Hangzhou, 310009, Zhejiang, China. hy0904@live.cn.
Yuan
Y
Hong
D000818:Animals; D002490:Central Nervous System / Q000293:injuries* / Q000473:pathology; D002712:Chlorides / Q000378:metabolism*; D006706:Homeostasis; D006801:Humans; D008954:Models, Biological; D058990:Molecular Targeted Therapy; D027981:Symporters / Q000737:chemistry / Q000378:metabolism*; D020196:Trauma, Nervous System / Q000378:metabolism* / Q000473:pathology; D000096922:K Cl- Cotransporters
D002712:Chlorides; D027981:Symporters; D000096922:K Cl- Cotransporters
Acute CNS injury; Chloride homeostasis; Excitability; KCC2; Neuron