Sodium channel currents in rat hippocampal NG2 glia: Characterization and contribution to resting membrane potential

We have recently reported that most of NG2 glycoprotein expressing glial cells, or NG2 glia, in rat hippocampus persistently express sodium channel currents (INa) during development, but little is known about its function. We report here that hippocampal NG2 glia recorded in either acute slices or freshly isolated preparations from postnatal days (P) 7–21 rats express low density INa (9.5–15.7 pA/pF) that is characterized by a fast activation and rapid inactivation kinetics with a tetrodotoxin (TTX) IC50 value of 39.3 nM. The INa expression correlated with a ∼25 mV more depolarized resting membrane potential (RMP) as compared with non-INa-expressing GLAST(+) astrocytes in situ at the same age. In the presence of the sodium channel blocker TTX (0.1 μM), these depolarized RMPs were negatively shifted by an average of 19 mV and 16 mV for INa-expressing glia recordings from in situ and freshly isolated preparations, respectively. The INa expressing glia actually showed a positive RMP (+12 mV) in the absence of potassium conductance that was inhibited to 0 mV by 0.1 μM TTX. Analysis of the INa activation/inactivation curves yields an INa “window current” at −40±20 mV, implying a persistent INa component being active around the NG2 glia RMP of ∼−45 mV. According to the constant-field equation analysis, this active INa component leads to a pNa/pK ratio of 0.14 at RMP which is ∼threefold higher than astrocytes (0.05). These results indicate that a TTX sensitive INa component in NG2 glia contributes significantly to the depolarized NG2 glia RMP in the developing brain.