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 (INa,T) and a smaller, inactivation‐resistant persistent Na+ current (INa,P). Both currents could be blocked with TTX. 2 The average current densities of INa,T and INa,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 INa,P but had no significant effect on the amplitude of INa,T. 4 Exposing CA1 neurons to hypoxia for more than 7 min caused an increase in the amplitude of INa,P. There was also a delayed decrease in the amplitude of INa,T. 5 I Na,P was more sensitive to the Na+ channel blockers TTX and lidocaine than INa,T. The IC50 for the effect of TTX on INa,P was 9.1 ± 1.2 nM whereas the IC50 for INa,T was 37.1 ± 1.2 nM, approximately 4‐fold higher. Lidocaine (lignocaine; 1 μM) reduced INa,P to 0.24 ± 0.15 of control (n= 4) whereas INa,T was essentially unaffected (0.99 ± 0.11, n= 4). 6 These results show that INa,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 INa,T.