Protein kinase C enhances human sodium channel hNav1.7 resurgent currents via a serine residue in the domain III-IV linker

  • FEBS Lett. 2014 Nov 3;588(21):3964-9. doi: 10.1016/j.febslet.2014.09.011.
Zhi-Yong Tan  1 ,  Birgit T Priest  2 ,  Jeffrey L Krajewski  2 ,  Kelly L Knopp  2 ,  Eric S Nisenbaum  2 ,  Theodore R Cummins  3
Affiliations
  • 1. Department of Pharmacology and Toxicology and Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN 46202, USA. Electronic address: [email protected].
  • 2. Lilly Research Laboratories, Indianapolis, IN 46285, USA.
  • 3. Department of Pharmacology and Toxicology and Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
PMID: 25240195 DOI: 10.1016/j.febslet.2014.09.011
Abstract

Resurgent sodium currents likely play a role in modulating neuronal excitability. Here we studied whether protein kinase C (PKC) activation can increase resurgent currents produced by the human Sodium Channel hNav1.7. We found that a PKC agonist significantly enhanced hNav1.7-mediated resurgent currents and this was prevented by PKC antagonists. The enhancing effects were replicated by two phosphorylation-mimicking mutations and were prevented by a phosphorylation-deficient mutation at a conserved PKC phosphorylation site (Serine 1479). Our results suggest that PKC can increase sodium resurgent currents through phosphorylation of a conserved Serine residue located in the domain III-IV linker of sodium channels.

Keywords
Mutation; Protein kinase C; Resurgent current; Sodium channel; Voltage clamp; hNav1.7.