Poster Presentation 2014 International Biophysics Congress

The γ subunit of Na+,K+-ATPase, FXYD2, is involved in inflammatory pain (#283)

Bing Cai , Feng Wang 1 , Kai-Cheng Li 1 , Xu-Ye Hu 2 , Ying-Jin Lu 1 , Qiong Wang 3 , Lan Bao 3 , Xu Zhang 1
  1. Institute of Neuroscience and State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
  2. Shanghai Clinical Center, Chinese Academy of Sciences/XuHui Central Hospital, Shanghai, China
  3. Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
Nociceptive afferent neurons of the dorsal root ganglion (DRG) express not only the α and β subunits of Na+,K+-ATPase (NKA) but also the γ subunit FXYDs. However, the localization and role of FXYDs are unclear in nociceptive transmission of DRG neurons. The present study showed that FXYD2, one γ subunit of NKA, is expressed in small DRG neurons, mainly in IB4+ DRG neurons. FXYD2 was co-localized with α1NKA in small DRG neurons. FXYD2 interacted with the α1NKA, and negatively regulated the NKA activity in a way independent of FSTL1. Loss of FXYD2 in FXYD2-deficient mice caused the hyperpolarization of membrane potential in IB4+ small DRG neurons, but had limited effects on the excitability of these IB4+ neurons under normal circumstance. Genetic deletion of FXYD2 led to the reduction of mean frequency of spontaneous excitatory postsynaptic currents (sEPSCs), indicating the inhibitory effects of FXYD2 on excitatory synaptic transmission. Furthermore, FXYD2-deficient mice showed no significant difference in basal nociceptive responses, formalin-induced acute nociceptive responses and CFA-induced thermal hyperalgesia in comparison with the littermates. FXYD2-deficient mice showed a normal initiation of mechanical allodynia induced by CFA injection, but could not maintain the long-lasting mechanical allodynia as showed in wild-type littermates. Although the expression of FXYD2 and NKA subunits did not change after peripheral inflammation, the interaction of FXYD2 and α1NKA was gradually increased and reached a peak level at the fourth day after peripheral inflammation. Such increased interaction could be responsible for reduction of NKA activity, depolarization of membrane potential in IB4+ small DRG neurons, facilitation of afferent synaptic transmission and maintenance of CFA-induced mechanical allodynia. Thus, the increased FXYD2 activity is a mechanism of the inflammation-induced persistent mechanical allodynia.