Sodium channel subtypes are differentially localized to pre- and post-synaptic sites in rat hippocampus

J Comp Neurol. 2017 Nov 1;525(16):3563-3578. doi: 10.1002/cne.24291. Epub 2017 Aug 11.


Voltage-gated Na+ channels (Nav ) modulate neuronal excitability, but the roles of the various Nav subtypes in specific neuronal functions such as synaptic transmission are unclear. We investigated expression of the three major brain Nav subtypes (Nav 1.1, Nav 1.2, Nav 1.6) in area CA1 and dentate gyrus of rat hippocampus. Using light and electron microscopy, we found labeling for all three Nav subtypes on dendrites, dendritic spines, and axon terminals, but the proportion of pre- and post-synaptic labeling for each subtype varied within and between subregions of CA1 and dentate gyrus. In the central hilus (CH) of the dentate gyrus, Nav 1.1 immunoreactivity was selectively expressed in presynaptic profiles, while Nav 1.2 and Nav 1.6 were expressed both pre- and post-synaptically. In contrast, in the stratum radiatum (SR) of CA1, Nav 1.1, Nav 1.2, and Nav 1.6 were selectively expressed in postsynaptic profiles. We next compared differences in Nav subtype expression between CH and SR axon terminals and between CH and SR dendrites and spines. Nav 1.1 and Nav 1.2 immunoreactivity was preferentially localized to CH axon terminals compared to SR, and in SR dendrites and spines compared to CH. No differences in Nav 1.6 immunoreactivity were found between axon terminals of CH and SR or between dendrites and spines of CH and SR. All Nav subtypes in both CH and SR were preferentially associated with asymmetric synapses rather than symmetric synapses. These findings indicate selective presynaptic and postsynaptic Nav expression in glutamatergic synapses of CH and SR supporting neurotransmitter release and synaptic plasticity.

Keywords: RRID:AB_2040003; RRID:AB_2040005; RRID:AB_2040202; RRID:CVCL_6911; RRID:SCR_002798; excitatory synapses.

MeSH terms

  • Action Potentials / drug effects
  • Action Potentials / genetics
  • Animals
  • Cells, Cultured
  • Embryo, Mammalian
  • HEK293 Cells
  • Hippocampus / cytology*
  • Humans
  • Male
  • NAV1.1 Voltage-Gated Sodium Channel / metabolism
  • NAV1.1 Voltage-Gated Sodium Channel / ultrastructure
  • NAV1.2 Voltage-Gated Sodium Channel / metabolism
  • NAV1.2 Voltage-Gated Sodium Channel / ultrastructure
  • NAV1.6 Voltage-Gated Sodium Channel / metabolism
  • NAV1.6 Voltage-Gated Sodium Channel / ultrastructure
  • Neuronal Plasticity / genetics
  • Neurons / physiology*
  • Neurons / ultrastructure
  • Post-Synaptic Density / drug effects
  • Post-Synaptic Density / metabolism*
  • Post-Synaptic Density / ultrastructure
  • Presynaptic Terminals / drug effects
  • Presynaptic Terminals / metabolism*
  • Presynaptic Terminals / ultrastructure
  • Protein Subunits / genetics
  • Protein Subunits / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Voltage-Gated Sodium Channels / genetics
  • Voltage-Gated Sodium Channels / metabolism*
  • Voltage-Gated Sodium Channels / ultrastructure


  • NAV1.1 Voltage-Gated Sodium Channel
  • NAV1.2 Voltage-Gated Sodium Channel
  • NAV1.6 Voltage-Gated Sodium Channel
  • Protein Subunits
  • Scn1a protein, mouse
  • Scn8a protein, mouse
  • Voltage-Gated Sodium Channels