title: FXYD2, a γ subunit of Na⁺, K⁺-ATPase, maintains persistent mechanical allodynia induced by inflammation.
abstract: Na⁺, K⁺-ATPase (NKA) is required to generate the resting membrane potential in neurons. Nociceptive afferent neurons express not only the α and β subunits of NKA but also the γ subunit FXYD2. However, the neural function of FXYD2 is unknown. The present study shows that FXYD2 in nociceptive neurons is necessary for maintaining the mechanical allodynia induced by peripheral inflammation. FXYD2 interacted with α1NKA and negatively regulated the NKA activity, depolarizing the membrane potential of nociceptive neurons. Mechanical allodynia initiated in FXYD2-deficient mice was abolished 4 days after inflammation, whereas it persisted for at least 3 weeks in wild-type mice. Importantly, the FXYD2/α1NKA interaction gradually increased after inflammation and peaked on day 4 post inflammation, resulting in reduction of NKA activity, depolarization of neuron membrane and facilitation of excitatory afferent neurotransmission. Thus, the increased FXYD2 activity may be a fundamental mechanism underlying the persistent hypersensitivity to pain induced by inflammation.
authors: Institute of Neuroscience and State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors: Feng
authors: F
authors: Wang
authors: Institute of Neuroscience and State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors: Bing
authors: B
authors: Cai
authors: Institute of Neuroscience and State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors: Kai-Cheng
authors: KC
authors: Li
authors: Shanghai Clinical Center, Chinese Academy of Sciences/XuHui Central Hospital, Shanghai, China.
authors: Xu-Ye
authors: XY
authors: Hu
authors: Institute of Neuroscience and State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors: Ying-Jin
authors: YJ
authors: Lu
authors: State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors: Qiong
authors: Q
authors: Wang
authors: 1] State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China [2] School of Life Science and Technology, ShanghaiTech University, Shanghai 200031, China.
authors: Lan
authors: L
authors: Bao
authors: 1] Institute of Neuroscience and State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China [2] School of Life Science and Technology, ShanghaiTech University, Shanghai 200031, China.
authors: Xu
authors: X
authors: Zhang
mesh_terms: D000818:Animals; D019556:COS Cells; D002460:Cell Line; D002522:Chlorocebus aethiops; D006930:Hyperalgesia / Q000503:physiopathology*; D007249:Inflammation / Q000503:physiopathology*; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D009619:Nociceptors / Q000378:metabolism / Q000502:physiology*; D010146:Pain / Q000503:physiopathology; D012333:RNA, Messenger / Q000235:genetics; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology
chemical_list: D012333:RNA, Messenger; C498816:Fxyd2 protein, mouse; D000254:Sodium-Potassium-Exchanging ATPase
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