Persistent sodium current in layer 5 neocortical neurons is primarily generated in the proximal axon

Nadav Astman, Michael J. Gutnick, Ilya A. Fleidervish

Research output: Contribution to journalArticlepeer-review

87 Scopus citations

Abstract

In addition to the well described fast-inactivating component of the Na+ current [transient Na+ current (INaT)], neocortical neurons also exhibit a low-voltage-activated, slowly inactivating "persistent" Na+ current (INaP), which plays a role in determining neuronal excitability and synaptic integration. We investigated the Na+ channels responsible for INaP in layer 5 pyramidal cells using cell-attached and whole-cell recordings in neocortical slices. In simultaneous cell-attached and whole-cell somatic recordings, no persistent Na+ channel activity was detected at potentials at which whole-cell INaP operates. Detailed kinetic analysis of late Na+ channel activity in cell-attached patches at 36°C revealed that somatic Na+ channels do not demonstrate "modal gating" behavior and that the probability of single late openings is extremely low (<1.4 × 10-4 or <0.02% of maximal open probability of INaT). Ensemble averages of these currents did not reveal a sustained component whose amplitude and voltage dependence could account for INaP as seen in whole-cell recordings. Local application of TTX to the axon blocked somatically recorded INaP, whereas somatic and dendritic application had little or no effect. Finally, simultaneous current-clamp recordings from soma and apical dendrite revealed that Na+ plateau potentials originate closer to the axon. Our data indicate that the primary source of INaP is in the spike initiation zone in the proximal axon. The focal axonal presence of regenerative subthreshold conductance with voltage and time dependence optimal to manipulate integration of synaptic input, spike threshold, and the pattern of repetitive firing provides the layer 5 pyramidal neuron with a mechanism for dynamic control of its gain.

Original languageEnglish
Pages (from-to)3465-3473
Number of pages9
JournalJournal of Neuroscience
Volume26
Issue number13
DOIs
StatePublished - 29 Mar 2006
Externally publishedYes

Keywords

  • Axon
  • Excitability
  • Layer 5 pyramidal neuron
  • Neocortex
  • Persistent sodium current
  • Sodium channel

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