Magi-1 scaffolds Na_V1.8 and Slack K_Na channels in dorsal root ganglion neurons regulating excitability and pain.

ABSTRACT: Voltage-dependent sodium (Na_V) 1.8 channels regulate action potential generation in nociceptive neurons, identifying them as putative analgesic targets. Here, we show that Na_V1.8 channel plasma membrane localization, retention, and stability occur through a direct interaction with the postsynaptic density-95/discs large/zonula occludens-1-and WW domain-containing scaffold protein called membrane-associated guanylate kinase with inverted orientation (Magi)-1. The neurophysiological roles of Magi-1 are largely unknown, but we found that dorsal root ganglion (DRG)-specific knockdown of Magi-1 attenuated thermal nociception and acute inflammatory pain and produced deficits in Na_V1.8 protein expression. A competing cell-penetrating peptide mimetic derived from t

SUBMITTER: Pryce KD 

PROVIDER: S-EPMC6529352 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature