Nuclear Factor-kappaB Gates Na(v)1.7 Channels in DRG Neurons via Protein-Protein Interaction

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(v)1.7 channels in the membrane of dorsal root ganglion (DRG) neurons of rats. The interaction increased Na(v)1.7 currents by slowing inactivation of Na(v)1.7 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(v)1.7 currents within 5 min but did not affect nuclear NF-κB within 40 min. This non-transcriptional effect on Na(v)1.7 may underlie a rapid regulation of the sensibility of the somatosensory system. Both NF-κB and Na(v)1.7 channels are critically implicated in many physiological functions and diseases. Our finding may shed new light on the investigation into the underlying mechanisms.