Nuclear Factor-kappaB Gates Nav1.7 Channels in DRG Neurons via Protein-Protein Interaction

Summary 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 Nav1.7 channels in the membrane of dorsal root ganglion (DRG) neurons of rats. The interaction increased Nav1.7 currents by slowing inactivation of Nav1.7 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 Nav1.7 currents within 5 min but did not affect nuclear NF-κB within 40 min. This non-transcriptional effect on Nav1.7 may underlie a rapid regulation of the sensibility of the somatosensory system. Both NF-κB and Nav1.7 channels are critically implicated in many physiological functions and diseases. Our finding may shed new light on the investigation into the underlying mechanisms.
Graphical Abstract
Highlights • NF-κB p-p65 interacts with Nav1.7 in the membrane of DRG neurons • The interaction is reversible, depending on the cytoplasmic p-p65 content • Reducing cytoplasmic p-p65 rapidly attenuates the interaction and Nav1.7 currents • The rapid effect on Nav1.7 channels is independent of p-p65 nuclear translocation
Biological Sciences; Neuroscience; Molecular Neuroscience; Cellular Neuroscience