Inhibition of oxidative metabolism increases persistent sodium current in rat CA1 hippocampal neurons

1. Whole-cell patch-clamp recordings from freshly dissociated rat CA1 neurons revealed a large transient Na⁺ current (I(Na,T)) and a smaller, inactivation-resistant persistent Na⁺ current (I(Na,P)). Both currents could be blocked with TTX. 2. The average current densities of I(Na,T) and I(Na,P) in thirty cells were 111.0 ± 9.62 and 0.87 ± 0.13 pA pF^-1, respectively. 3. Inhibiting oxidative phosphorylation by adding 5 mM sodium cyanide to the pipette solution significantly increased the amplitude of I(Na,P) but had no significant effect on the amplitude of I(Na,T) 4. Exposing CA1 neurons to hypoxia for more than 7 min caused an increase in the amplitude of I(Na,P). There was also a delayed decrease in the amplitude of I(Na,T). 5. I(Na,P) was more sensitive to the Na⁺ channel blockers TTX and lidocaine than I(Na,T). The IC₅₀ for the effect of TTX on I(Na,P) was 9.1 ± 1.2 nM whereas the IC₅₀ for I(Na,T) was 37.1 ± 1.2 nM, approximately 4-fold higher. Lidocaine (lignocaine; 1 μm) reduced I(Na,P) to 0.24 ± 0.15 of control (n = 4) whereas I(Na,T) was essentially unaffected (0.99 ± 0.11, n = 4). 6. These results show that I(Na,P) is increased when oxidative metabolism is blocked in CA1 neurons. The persistent influx of Na⁺ through non-inactivating Na⁺ channels can be blocked by concentrations of Na⁺ channel blockers that do not affect I(Na,T).