Premium
Protein kinase C enhances human sodium channel hNav1.7 resurgent currents via a serine residue in the domain III–IV linker
Author(s) -
Tan Zhi-Yong,
Priest Birgit T.,
Krajewski Jeffrey L.,
Knopp Kelly L.,
Nisenbaum Eric S.,
Cummins Theodore R.
Publication year - 2014
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2014.09.011
Subject(s) - phosphorylation , serine , protein kinase c , sodium channel , kinase , linker , chemistry , threonine , residue (chemistry) , protein kinase domain , microbiology and biotechnology , sodium , biochemistry , biophysics , biology , mutant , organic chemistry , computer science , gene , operating system
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.