Functional properties and differential neuromodulation of Na(v)1.6 channels

Mol Cell Neurosci. 2008 Aug;38(4):607-15. doi: 10.1016/j.mcn.2008.05.009. Epub 2008 May 20.


The voltage-gated sodium channel Na(v)1.6 plays unique roles in the nervous system, but its functional properties and neuromodulation are not as well established as for Na(V)1.2 channels. We found no significant differences in voltage-dependent activation or fast inactivation between Na(V)1.6 and Na(V)1.2 channels expressed in non-excitable cells. In contrast, the voltage dependence of slow inactivation was more positive for Na(v)1.6 channels, they conducted substantially larger persistent sodium currents than Na(v)1.2 channels, and they were much less sensitive to inhibition by phosphorylation by cAMP-dependent protein kinase and protein kinase C. Resurgent sodium current, a hallmark of Na(v)1.6 channels in neurons, was not observed for Na(V)1.6 expressed alone or with the auxiliary beta(4) subunit. The unique properties of Na(V)1.6 channels, together with the resurgent currents that they conduct in neurons, make these channels well-suited to provide the driving force for sustained repetitive firing, a crucial property of neurons.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Action Potentials / physiology*
  • Animals
  • Cell Line
  • Humans
  • Mice
  • NAV1.6 Voltage-Gated Sodium Channel
  • Nerve Tissue Proteins / chemistry
  • Nerve Tissue Proteins / metabolism
  • Nerve Tissue Proteins / physiology*
  • Rats
  • Receptors, Neurotransmitter / physiology
  • Sodium Channels / chemistry
  • Sodium Channels / metabolism
  • Sodium Channels / physiology*


  • NAV1.6 Voltage-Gated Sodium Channel
  • Nerve Tissue Proteins
  • Receptors, Neurotransmitter
  • Scn8a protein, mouse
  • Sodium Channels