Protein Kinase C Controls the Excitability of Cortical Pyramidal Neurons by Regulating Kv2.2 Channel Activity  

作　　者：Zhaoyang Li Wenhao Dong Xinyuan Zhang Jun-Mei Lu Yan-Ai Mei Changlong Hu 

机构地区：[1]State Key Laboratory of Medical Neurobiology,Institutes of Brain Science and School of Life Sciences,Fudan University,Shanghai 200438,China

出　　处：《Neuroscience Bulletin》2022年第2期135-148,共14页神经科学通报（英文版）

基　　金：supported by the National Natural Science Foundation of China(31771282);the China Postdoctoral Science Foundation(BX20200093 and 2021M690038).

摘　　要：The family of voltage-gated potassium Kv2 channels consists of the Kv2.1 and Kv2.2 subtypes.Kv2.1 is constitutively highly phosphorylated in neurons and its function relies on its phosphorylation state.Whether the function of Kv2.2 is also dependent on its phosphorylation state remains unknown.Here,we investigated whether Kv2.2 channels can be phosphorylated by protein kinase C(PKC)and examined the effects of PKC-induced phosphorylation on their activity and function.Activation of PKC inhibited Kv2.2 currents and altered their steadystate activation in HEK293 cells.Point mutations and specific antibodies against phosphorylated S481 or S488 demonstrated the importance of these residues for the PKC-dependent modulation of Kv2.2.In layer Ⅱ pyramidal neurons in cortical slices,activation of PKC similarly regulated native Kv2.2 channels and simultaneously reduced the frequency of action potentials.In conclusion,this study provides the first evidence to our knowledge that PKC-induced phosphorylation of the Kv2.2 channel controls the excitability of cortical pyramidal neurons.

关 键 词：Kv2.2 PKC PHOSPHORYLATION Pyramidal neurons EXCITABILITY 

分 类 号：R338[医药卫生—人体生理学]