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. INa,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 microM) 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.
Hammarstrom
A K
AK
Membrane Biology Program, John Curtin School of Medical Research, Australian National University, PO Box 334, Canberra, ACT 2601, Australia. anna.hammarstrom@anu.edu.au
Gage
P W
PW
D000818:Animals; D004558:Electric Stimulation; D004594:Electrophysiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008012:Lidocaine / Q000494:pharmacology; D008564:Membrane Potentials / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D010084:Oxidation-Reduction; D010085:Oxidative Phosphorylation / Q000187:drug effects; D018408:Patch-Clamp Techniques; D051381:Rats; D015222:Sodium Channels / Q000187:drug effects / Q000378:metabolism*; D012966:Sodium Cyanide / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology
D004791:Enzyme Inhibitors; D015222:Sodium Channels; D013779:Tetrodotoxin; D008012:Lidocaine; D012966:Sodium Cyanide