Persistent sodium current modulates axonal excitability in CA1 pyramidal neurons

• Verfasst von: Müller, Peter [VerfasserIn]
• Verfasst von: Draguhn, Andreas [VerfasserIn]
• Verfasst von: Egorov, Alexei [VerfasserIn]
• Titel: Persistent sodium current modulates axonal excitability in CA1 pyramidal neurons
• Verf.angabe: Peter Müller, Andreas Draguhn and Alexei V. Egorov
• E-Jahr: 2018
• Jahr: 04 June 2018
• Umfang: 13 S.
• Fussnoten: Gesehen am 13.05.2019
• Titel Quelle: Enthalten in: Journal of neurochemistry
• Ort Quelle: Oxford : Wiley-Blackwell, 1956
• Jahr Quelle: 2018
• Band/Heft Quelle: 146(2018), 4, Seite 446-458
• ISSN Quelle: 1471-4159
• DOI: doi:10.1111/jnc.14479
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: axon
• Sach-SW: ectopic action potential
• Sach-SW: hippocampal slice
• Sach-SW: persistent sodium current
• Sach-SW: phenytoin
• Sach-SW: riluzole
• K10plus-PPN: 1665291966

Abstract

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.