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

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

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.

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