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