Mechanism of charged interface of stargazin EX1 on AMPAR opening and desensitization  

作　　者：YANG Zu-xiao ZHANG Wei 

机构地区：[1]Department of Pharmacology of Chinese Materia Medica,Institution of Chinese Integrative Medicine,the Key Laboratory of New Drug Pharmacology and Toxicology,Hebei Medical University,Shijiazhuang 050017,China

出　　处：《中国药理学与毒理学杂志》2021年第9期685-686,共2页Chinese Journal of Pharmacology and Toxicology

摘　　要：OBJECTIVE AMPA-subtype iono⁃tropic glutamate receptors(iGluRs)mediate fast excitatory synaptic transmission in the mammali⁃an central nervous system(CNS).It plays the key role in many central nerves disorder such as epilepsy,depression and schizophrenia.Star⁃gazin(STZ,also named TARP-γ2),as the first TARPs found in CNS,potentiates AMPAR activity by attenuating deactivation and desensitization,enhancing recovery from desensitization,and facilitating agonist affinity and efficacy.However,it is still not fully understanding howγ-2 modu⁃late AMPAR gating.METHODS AND RESULTS The desensitization for different mutation of AMPAR andγ-2 was compared.It was shown that the electric attraction was involved in the interaction of AMPAR andγ-2.In addition,the interaction of KGK motif in ligand binding domain and pre-M1 chain of AMPAR and EX1 ofγ-2 modulate AMPAR opening and desensitization.Substitution of these charged residues had sur⁃prisingly effects on AMPAR desensitization kinet⁃ics.CONCLUSION The electric attraction has two impacts on the channels gating process the first destablizing the receptor closed state and enabling the channel opening,the second pro⁃moting the channels entering desensitization state upon the channel opening.

关 键 词：ionotropic glutamate receptors DESENSITIZATION stargazin EX1 

分 类 号：R338[医药卫生—人体生理学]