Role of the cation-chloride-cotransporters in the circadian system  

作　　者：Shihan Salihu Nur Farah Meor Azlan Sunday Solomon Josiah Zhijuan Wu Yun Wang Jinwei Zhang 

机构地区：[1]Institute of Biomedical and Clinical Sciences,Medical School,College of Medicine and Health,University of Exeter,Hatherly Laboratories,Exeter EX44PS,UK [2]Department of Neurology,Institutes of Brain Science,State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science,Institute of Biological Science,Zhongshan Hospital,Fudan University,Shanghai 200032,China

出　　处：《Asian Journal of Pharmaceutical Sciences》2021年第5期589-597,共9页亚洲药物制剂科学（英文）

基　　金：supported by a Commonwealth Ph D Scholarship(S.S.J.);NSFC grants to Y.W.(31771188,31471027);the University of Exeter Medical School start-up fund(J.Z.);NIH Grants R01 NS109358(J.Z.)。

摘　　要：The circadian system plays an immense role in controlling physiological processes in our body.The suprachiasmatic nucleus (SCN) supervises this system,regulating and harmonising the circadian rhythms in our body.Most neurons present in the SCN are GABAergic neurons.Although GABA is considered the main inhibitory neurotransmitter of the CNS,recent studies have shown that excitatory responses were recorded in this area.These responses are enabled by an increase in intracellular chloride ions[Cl;];levels.The chloride (Cl;) levels in GABAergic neurons are controlled by two solute carrier 12 (SLC12)cation-chloride-cotransporters (CCCs):Na^(+)/K^(+)/Cl^(-)co-transporter (NKCC1) and K^(+)/Cl^(-)cotransporter (KCC2),that respectively cause an influx and efflux of Cl^(-).Recent works have found altered expression and/or activity of either of these co-transporters in SCN neurons and have been associated with circadian rhythms.In this review,we summarize and discuss the role of CCCs in circadian rhythms,and highlight these recent advances which attest to CCC’s growing potential as strong research and therapeutic targets.

关 键 词：GABAERGIC Na^(+)-K^(+)-2Cl^(-)cotransporter 1(NKCC1) K^(+)-2Cl^(-)cotransporter 2(KCC2) WNK3-SPAK/OSR1 Chloride(Cl^(-)) homoostasis Suprachiasmatic nucleus(SCN) Circadian rhythms 

分 类 号：R74[医药卫生—神经病学与精神病学]