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您的检索式：作者名="LAI Dongwu"
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| 1 | Molecular basis for ligand activation of the human KCNQ2 channel显示文摘The voltage-gated potassium channel KCNQ2 is responsible for M-current in neurons and is an important drug target to treat epilepsy,pain and several other diseases related to neuronal hyper-excitability.A list of synthetic compounds have been developed to directly activate KCNQ2,yet our knowledge of their activation mechanism is limited,due to lack of high-resolution structures.Here,we report cryo-electron microscopy(cryo-EM)structures of the human KCNQ2 determined in apo state and in complex with two activators,ztz240 or retigabine,which activate KCNQ2 through different mechanisms.The activator-bound structures,along with electrophysiology analysis,reveal that ztz240 binds at the voltage-sensing domain and directly stabilizes it at the activated state,whereas retigabine binds at the pore domain and activates the channel by an allosteric modulation.By accurately defining ligand-binding sites,these KCNQ2 structures not only reveal different ligand recognition and activation mechanisms,but also provide a structural basis for drug optimization and design. | Xiaoxiao Li Qiansen Zhangc Peipei Guo Jie Fu Lianghe Mei Dashuai Lv Jiangqin Wang Dongwu Lai Sheng Ye Huaiyu Yang Jiangtao Guo | 2021 | Cell Research2021，31，1： | 3 |
| 2 | Stretch current- induced abnormal impulses in CaMKIIδ knockout mouse ven- tricular myocytes 显示文摘 | LAI Dongwu XU Lin CHENG Jun | 2013 | J Cardiovasc Electrophysiol2013，24，4： | 1 |
| 3 | Structural basis for the gating modulation of Kv4.3 by auxiliary subunits显示文摘Dear Editor,Kv4.3 is an A-type voltage-gated potassium channel that is characterized by fast activation at subthreshold membrane potentials,rapid inactivation,and quick recovery from inactiva-tionJ In neurons,Kv4.3 conducts the transient subthreshold somatodendritic A-type potassium current(Isa),knock down of which results in neuropathic pain and epilepsy.2 In cardiomyocytes,Kv4.3 generates the transient outward potassium current(lto)and its dysfunction is related to a variety of heart diseases,such as hypertrophy,heart failure,myocardial infarction,heart valvular disease,atrial fibrillation,and diabetic cardiomyopathy. | Demin Ma Cheng Zhao Xiaochen Wang Xiaoxiao Yi Zha Yan Zhang Guosheng Fu Ping Liang Jiangtao Guo Dongwu Lai | 2022 | Cell Research2022，32，4： | 0 |
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