Persistent sodium current modulates axonal excitability in CA1 pyramidal neurons / Peter Müller, Andreas Draguhn and Alexei V. Egorov

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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Persons: Müller, Peter [Author]; Draguhn, Andreas [Author]; Egorov, Alexei [Author]
Format: eArticle
Language(s):English
Publication:04 June 2018
Part of:Journal of neurochemistry 146(2018), 4, Seite 446-458
Subjects:axon
ectopic action potential
hippocampal slice
persistent sodium current
phenytoin
riluzole
Notes:Gesehen am 13.05.2019
Physical description:13
ISSN:1471-4159
DOI:10.1111/jnc.14479