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

A. K. M. Hammarström and P. W. Gage

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.

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