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

TitleSodium channel subtypes are differentially localized to pre- and post-synaptic sites in rat hippocampus.
Publication TypeJournal Article
Year of Publication2017
AuthorsJohnson KW, Herold KF, Milner TA, Hemmings HC, Platholi J
JournalJ Comp Neurol
Date Published2017 Nov 01
KeywordsAction Potentials, Animals, Cells, Cultured, Embryo, Mammalian, HEK293 Cells, Hippocampus, Humans, Male, NAV1.1 Voltage-Gated Sodium Channel, NAV1.2 Voltage-Gated Sodium Channel, NAV1.6 Voltage-Gated Sodium Channel, Neuronal Plasticity, Neurons, Post-Synaptic Density, Presynaptic Terminals, Protein Subunits, Rats, Rats, Sprague-Dawley, Voltage-Gated Sodium Channels

Voltage-gated Na channels (Na ) modulate neuronal excitability, but the roles of the various Na subtypes in specific neuronal functions such as synaptic transmission are unclear. We investigated expression of the three major brain Na subtypes (Na 1.1, Na 1.2, Na 1.6) in area CA1 and dentate gyrus of rat hippocampus. Using light and electron microscopy, we found labeling for all three Na 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, Na 1.1 immunoreactivity was selectively expressed in presynaptic profiles, while Na 1.2 and Na 1.6 were expressed both pre- and post-synaptically. In contrast, in the stratum radiatum (SR) of CA1, Na 1.1, Na 1.2, and Na 1.6 were selectively expressed in postsynaptic profiles. We next compared differences in Na subtype expression between CH and SR axon terminals and between CH and SR dendrites and spines. Na 1.1 and Na 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 Na 1.6 immunoreactivity were found between axon terminals of CH and SR or between dendrites and spines of CH and SR. All Na subtypes in both CH and SR were preferentially associated with asymmetric synapses rather than symmetric synapses. These findings indicate selective presynaptic and postsynaptic Na expression in glutamatergic synapses of CH and SR supporting neurotransmitter release and synaptic plasticity.

Alternate JournalJ Comp Neurol
PubMed ID28758202
PubMed Central IDPMC5927368
Grant ListR01 DA008259 / DA / NIDA NIH HHS / United States
R01 GM058055 / GM / NIGMS NIH HHS / United States