Nuclear Factor-kappaB Gates Na_v1.7 Channels in DRG Neurons via Protein-Protein Interaction.

ABSTRACT: It is well known that nuclear factor-kappaB (NF-κB) regulates neuronal structures and functions by nuclear transcription. Here, we showed that phospho-p65 (p-p65), an active form of NF-κB subunit, reversibly interacted with Na_v1.7 channels in the membrane of dorsal root ganglion (DRG) neurons of rats. The interaction increased Na_v1.7 currents by slowing inactivation of Na_v1.7 channels and facilitating their recovery from inactivation, which may increase the resting state of the channels ready for activation. In cultured DRG neurons TNF-α upregulated the membrane p-p65 and enhanced Na_v1.7 currents within 5 min but did not affect nuclear NF-κB within 40 min. This non-transcriptional effect on Na_v1.7 may underlie a rapid regulation of the sensibility of the somatosensory system. Both NF-κB and Na_v1.7 channels are critically implicated in many physiological functions and diseases. Our finding may shed new light on the investigation into the underlying mechanisms.

SUBMITTER: Xie MX 

PROVIDER: S-EPMC6715905 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature