Involvement of nuclear factor‐kappa B in superoxide‐lowered protein expression of voltage‐gated sodium channels in nodose ganglia from heart failure rats

Our previous study has shown that chronic heart failure (CHF) elevates mitochondria‐derived superoxide level and reduces protein expression of voltage‐gated sodium (Na v ) channels in rat nodose neurons. In the present study, we investigated the involvement of mitochondrial superoxide and nuclear factor‐kappa B (NF‐kB) in CHF‐decreased Na v 1.7 channel expression in rat nodose ganglia. CHF was induced by left coronary ligation. Adenoviral MnSOD (Ad.MnSOD) gene (4 × 10 10 PFU/ml, 1 μl) or lentiviral NF‐kB (p65) shRNA (5 × 10 6 IFU/ml, 1 μl) was injected into the nodose ganglia. Mitochondrial superoxide was detected using mitochondria‐targeted superoxide sensitive flurogenic probe MitoSOX. MnSOD, NF‐kB (p65) and Na v 1.7 expression were measured by western blot. NF‐κB binding to the promoter of Na v 1.7 channels was detected with chromosome immunoprecipitation assay (ChIP). We found that: 1) HF decreased Na v 1.7 expression, increased NF‐kB (p65) phosphorylation and NF‐kB (p65) binding with Na v 1.7 promoter; 2) NF‐kB (p65) shRNA reduced total and phosphorylated NF‐kB (p65) and increased Na v 1.7 expression in CHF nodese neurons; 3) Ad.MnSOD transfection elevated MnSOD protein, reduced the elevation of mitochondrial superoxide level and phosphorylated NF‐kB (p65), and increased Na v 1.7 expression in the nodose ganglia from CHF rat. These results indicate that mitochondrial superoxide overproduction triggered NF‐kB activation and subsequently depressed Na v 1.7 expression in CHF nodose neurons.