Browsing by Subject "Electrophysiological Processes"

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    Protein kinase C enhances human sodium channel hNav1.7 resurgent currents via a serine residue in the domain III-IV linker
    (Elsevier, 2014-11-03) Tan, Zhi-Yong; Priest, Birgit T.; Krajewski, Jeffrey L.; Knopp, Kelly L.; Nisenbaum, Eric S.; Cummins, Theodore R.; Department of Pharmacology and Toxicology, IU School of Medicine
    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.