Persistent sodium current modulates axonal excitability in CA1 pyramidal neurons
Axonal excitability is an important determinant for the accuracy, direction, and velocity of neuronal signaling. The mechanisms underlying spike generation in the axonal initial segment and transmitter release from presynaptic terminals have been intensely studied and revealed a role for several spe...
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| Hauptverfasser: | , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
04 June 2018
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| In: |
Journal of neurochemistry
Year: 2018, Jahrgang: 146, Heft: 4, Pages: 446-458 |
| ISSN: | 1471-4159 |
| DOI: | 10.1111/jnc.14479 |
| Online-Zugang: | Verlag, Pay-per-use, Volltext: https://doi.org/10.1111/jnc.14479 Verlag, Pay-per-use, Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1111/jnc.14479 
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| Verfasserangaben: | Peter Müller, Andreas Draguhn and Alexei V. Egorov |
| Zusammenfassung: | Axonal excitability is an important determinant for the accuracy, direction, and velocity of neuronal signaling. The mechanisms underlying spike generation in the axonal initial segment and transmitter release from presynaptic terminals have been intensely studied and revealed a role for several specific ionic conductances, including the persistent sodium current (INaP). Recent evidence indicates that action potentials can also be generated at remote locations along the axonal fiber, giving rise to ectopic action potentials during physiological states (e.g., fast network oscillations) or in pathological situations (e.g., following demyelination). Here, we investigated how ectopic axonal excitability of mouse hippocampal CA1 pyramidal neurons is regulated by INaP. Recordings of field potentials and intracellular voltage in brain slices revealed that electrically evoked antidromic spikes were readily suppressed by two different blockers of INaP, riluzole and phenytoin. The effect was mediated by a reduction of the probability of ectopic spike generation while latency was unaffected. Interestingly, the contribution of INaP to excitability was much more pronounced in axonal branches heading toward the entorhinal cortex compared with the opposite fiber direction toward fimbria. Thus, excitability of distal CA1 pyramidal cell axons is affected by persistent sodium currents in a direction-selective manner. This mechanism may be of importance for ectopic spike generation in oscillating network states as well as in pathological situations. |
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| Beschreibung: | Gesehen am 13.05.2019 |
| Beschreibung: | Online Resource |
| ISSN: | 1471-4159 |
| DOI: | 10.1111/jnc.14479 |