FGF13 Selectively Regulates Heat Nociception by Interacting with Nav1.7.
The current knowledge about heat nociception is mainly confined to the thermosensors, including the transient receptor potential cation channel V1 expressed in the nociceptive neurons of dorsal root ganglion (DRG). However, the loss of thermosensors only partially impairs heat nociception, suggesting the existence of undiscovered mechanisms. We found that the loss of an intracellular fibroblast growth factor (FGF), FGF13, in the mouse DRG neurons selectively abolished heat nociception. The noxious heat stimuli could not evoke the sustained action potential firing in FGF13-deficient DRG neurons. Furthermore, FGF13 interacted with the sodium channel Nav1.7 in a heat-facilitated manner. FGF13 increased Nav1.7 sodium currents and maintained the membrane localization of Nav1.7 during noxious heat stimulation, enabling the sustained firing of action potentials. Disrupting the FGF13/Nav1.7 interaction reduced the heat-evoked action potential firing and nociceptive behavior. Thus, beyond the thermosensors, the FGF13/Nav1.7 complex is essential for sustaining the transmission of noxious heat signals.
Institute of Neuroscience and State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Liu
L
Yang
Institute of Neuroscience and State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Fei
F
Dong
Shanghai Clinical Research Center, Chinese Academy of Sciences/XuHui Central Hospital, Shanghai 200031, China.
Qing
Q
Yang
Department of Radiology and Radiological Science, Institute of Imaging Science, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Pai-Feng
PF
Yang
Key Laboratory of Magnetic Resonance in Biological Systems and State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences, Wuhan 430071, China.
Ruiqi
R
Wu
Institute of Neuroscience and State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Qing-Feng
QF
Wu
Institute of Neuroscience and State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Dan
D
Wu
Institute of Neuroscience and State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Chang-Lin
CL
Li
Institute of Neuroscience and State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Yan-Qing
YQ
Zhong
Institute of Neuroscience and State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Ying-Jin
YJ
Lu
Discipline of Neuroscience and Department of Anatomy, Histology and Embryology, Collaborative Innovation Center for Brain Science, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China.
Xiaoyang
X
Cheng
Key Laboratory of Magnetic Resonance in Biological Systems and State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences, Wuhan 430071, China.
Fu-Qiang
FQ
Xu
Shanghai Clinical Research Center, Chinese Academy of Sciences/XuHui Central Hospital, Shanghai 200031, China; Department of Radiology and Radiological Science, Institute of Imaging Science, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Limin
L
Chen
State Key Laboratory of Cell Biology, CAS Center for Excellence in Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China; School of Life Science and Technology, ShanghaiTec University, Shanghai 201210, China.
Lan
L
Bao
Institute of Neuroscience and State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China; School of Life Science and Technology, ShanghaiTec University, Shanghai 201210, China. Electronic address: xu.zhang@ion.ac.cn.
Xu
X
Zhang
D000200:Action Potentials / Q000502:physiology; D000818:Animals; D002478:Cells, Cultured; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000378:metabolism*; D005727:Ganglia, Spinal / Q000378:metabolism*; D006358:Hot Temperature; D006801:Humans; D008822:Mice, Transgenic; D062556:NAV1.7 Voltage-Gated Sodium Channel / Q000235:genetics* / Q000378:metabolism*; D009474:Neurons / Q000502:physiology*
D062556:NAV1.7 Voltage-Gated Sodium Channel; C486866:SCN9A protein, human; C503479:Scn9a protein, mouse; C108111:fibroblast growth factor 13; D005346:Fibroblast Growth Factors
FGF13; brain imaging; heat nociception; sensory neuron; sodium channel; thermosensor