Effects of lidocaine reversible inactivation of the median raphe nucleus on long-term potentiation and recurrent inhibition in the dentate gyrus of rat hippocampus

Hydrogen peroxide (H₂O₂) causes oxidative stress and is considered a mediator of cell death in various organisms. Our previous studies showed that prolonged (>6 h) treatment of Aplysia sensory neurons with 1 mM H₂O₂ produced hyperpolarization of the resting membrane potential, followed by apoptotic morphological changes. In this study, we examined the effect of H₂O₂ on the membrane conductance of Aplysia sensory neurons. Hyperpolarization was induced by 10 mM H₂O₂ within 1 h, and this was attributed to increased membrane conductance. In addition, treatment with 10 mM H₂O₂ for 3 min produced immediate depolarization, which was due to decreased membrane conductance. The H₂O₂-induced hyperpolarization and depolarization were completely blocked by dithiothreitol, a disulfide-reducing agent. The later increase of membrane conductance induced by H₂O₂ was completely blocked by 100 mM TEA, a K⁺ channel blocker, suggesting that H₂O₂-induced hyperpolarization is due to the activation of K⁺ conductance. However, the inhibition of K⁺ efflux by TEA did not protect against H₂O₂-induced cell death in cultured Aplysia sensory neurons, which indicates that the signal pathway leading to H₂O₂-induced cell death is more complicated than expected.