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Nitric oxide increases persistent sodium current in rat hippocampal neurons
1Membrane Biology Program, John Curtin School of Medical Research, Australian National University, PO Box 334, Canberra, ACT, 2601 Australia. anna.hammarstrom@anu.edu.au
The Journal of Physiology
|October 16, 1999
Summary
Nitric oxide (NO) selectively enhances persistent sodium currents (INa,p) in rat hippocampal neurons by increasing channel activity. This NO-induced effect on INa,p can be reversed by reducing agents and lidocaine.
Area of Science:
- Neuroscience
- Molecular Biology
- Ion Channel Physiology
Background:
- Neuronal sodium channels are crucial for action potential generation and propagation.
- Persistent sodium currents (INa,p) contribute to neuronal excitability and have been implicated in various neurological conditions.
- The role of nitric oxide (NO) in modulating ion channel function, particularly sodium channels, remains an area of active investigation.
Purpose of the Study:
- To investigate the effects of nitric oxide (NO) donors on whole-cell and single-channel sodium currents in rat hippocampal neurons.
- To determine whether NO selectively modulates transient (INa,t) or persistent (INa,p) sodium currents.
- To elucidate the potential mechanism underlying NO's effect on sodium channel activity.
Main Methods:
- Whole-cell patch-clamp recordings were performed on acutely dissociated and cultured rat hippocampal neurons.
- The effects of two NO donors, sodium nitroprusside (SNP) and S-nitroso-N-acetyl-DL-penicillamine (SNAP), on sodium currents were assessed.
- Single-channel recordings in excised inside-out patches were used to examine the activity of persistent sodium channels.
Main Results:
- NO donors (SNP and SNAP) significantly increased the amplitude of whole-cell persistent sodium currents (INa,p) by 60-80% without affecting transient sodium currents (INa,t).
- In excised patches, both SNP and SNAP enhanced mean persistent sodium channel activity, with SNP showing a more pronounced effect.
- The NO-induced increase in persistent Na+ channel activity was reversible by the reducing agent dithiothreitol (DTT) and lidocaine, suggesting an oxidation-dependent mechanism.
Conclusions:
- Nitric oxide selectively enhances the activity of neuronal persistent sodium channels (INa,p) in rat hippocampal neurons.
- The findings suggest that NO may directly modulate Na+ channel function through an oxidizing action on the channel protein or associated regulatory proteins.
- This modulation of INa,p by NO could have significant implications for neuronal excitability and function in physiological and pathological states.