Tumor necrosis factor α modulates sodium-activated potassium channel SLICK in rat dorsal horn neurons via p38 MAPK activation pathway

Abstract

The dorsal horn (DH) of the spinal cord is the integrative center that processes and transmits pain sensation. Abnormal changes in ion channel expression can enhance the excitability of pain-related DH neurons. Sodium-activated potassium (K_Na) channels are highly expressed particularly in the central nervous system; however, information about whether rat DH neurons express the SLICK channel protein is lacking, and the direct effects on SLICK in response to inflammation and the potential signaling pathway mediating such effects are yet to be elucidated. Here, using cultured DH neurons, we have shown that tumor necrosis factor-α inhibits the total outward potassium current I_K and the K_Na current predominantly as well as induces a progressive loss of firing accommodation. However, we found that this change in channel activity is offset by the p38 inhibitor SB202190, thereby suggesting the modulation of SLICK channel activity via the p38 MAPK pathway. Furthermore, we have demonstrated that the tumor necrosis factor-α modulation of K_Na channels does not occur at the level of SLICK channel gating but arises from possible posttranslational modification.

Keywords:

• p38 MAPK
• SLICK channel
• neuropathic pain
• dorsal horn
• TNF-α

Acknowledgments

The work was supported by the National Natural Science Foundation of China (Nos. 81572170 and 81572109). The authors thank Zi-Kai Zhou (Southeast University) for expert technical assistance. They also thank American Journal Expert for language polishing.

Disclosure

The authors report no conflicts of interest in this work.