title: Nav1.9 expression in magnocellular neurosecretory cells of supraoptic nucleus.
abstract: Osmoregulation in mammals is tightly controlled by the release of vasopressin and oxytocin from magnocellular neurosecretory cells (MSC) of the supraoptic nucleus (SON). The release of vasopressin and oxytocin in the neurohypophysis by axons of MSC is regulated by bursting activity of these neurons, which is influenced by multiple sources, including intrinsic membrane properties, paracrine contributions of glial cells, and extrinsic synaptic inputs. Previous work has shown that bursting activity of MSC is tetrodotoxin (TTX)-sensitive, and that TTX-S sodium channels Nav1.2, Nav1.6 and Nav1.7 are expressed by MSC and upregulated in response to osmotic challenge in rats. The TTX-resistant sodium channels, NaV1.8 and Nav1.9, are preferentially expressed, at relatively high levels, in peripheral neurons, where their properties are linked to repetitive firing and subthreshold electrogenesis, respectively, and are often referred to as "peripheral" sodium channels. Both sodium channels have been implicated in pain pathways, and are under study as potential therapeutic targets for pain medications which might be expected to have minimal CNS side effects. We show here, however, that Nav1.9 is expressed by vasopressin- and oxytocin-producing MSC of the rat supraoptic nucleus (SON). We also show that cultured MSC exhibit sodium currents that have characteristics of Nav1.9 channels. In contrast, Nav1.8 is not detectable in the SON. These results suggest that Nav1.9 may contribute to the firing pattern of MSC of the SON, and that careful assessment of hypothalamic function be performed as NaV1.9 blocking agents are studied as potential pain therapies.
authors.affiliation: Department of Neurology and Center for Neuroscience and Regeneration Research, Yale University School of Medicine, New Haven, CT 06510, USA; Rehabilitation Research Center, VA Connecticut Healthcare System, West Haven, CT 06516, USA. Electronic address: joel.black@yale.edu.
authors.forename: J A
authors.initials: JA
authors.lastname: Black
authors.affiliation: Department of Neurology and Center for Neuroscience and Regeneration Research, Yale University School of Medicine, New Haven, CT 06510, USA; Rehabilitation Research Center, VA Connecticut Healthcare System, West Haven, CT 06516, USA. Electronic address: dmytro.vasylyev@yale.edu.
authors.forename: D
authors.initials: D
authors.lastname: Vasylyev
authors.affiliation: Department of Neurology and Center for Neuroscience and Regeneration Research, Yale University School of Medicine, New Haven, CT 06510, USA; Rehabilitation Research Center, VA Connecticut Healthcare System, West Haven, CT 06516, USA. Electronic address: sulayman.dib-hajj@yale.edu.
authors.forename: S D
authors.initials: SD
authors.lastname: Dib-Hajj
authors.affiliation: Department of Neurology and Center for Neuroscience and Regeneration Research, Yale University School of Medicine, New Haven, CT 06510, USA; Rehabilitation Research Center, VA Connecticut Healthcare System, West Haven, CT 06516, USA. Electronic address: stephen.waxman@yale.edu.
authors.forename: S G
authors.initials: SG
authors.lastname: Waxman
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004558:Electric Stimulation; D015870:Gene Expression / Q000502:physiology*; D015640:Ion Channel Gating / Q000187:drug effects; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000235:genetics; D062558:NAV1.9 Voltage-Gated Sodium Channel / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D010121:Oxytocin / Q000378:metabolism; D018408:Patch-Clamp Techniques; D051381:Rats; D026941:Sodium Channel Blockers / Q000494:pharmacology; D013495:Supraoptic Nucleus / Q000166:cytology*; D013779:Tetrodotoxin / Q000494:pharmacology; D014667:Vasopressins / Q000378:metabolism
chemical_list: D062558:NAV1.9 Voltage-Gated Sodium Channel; C113705:Scn11a protein, rat; D026941:Sodium Channel Blockers; D014667:Vasopressins; D013779:Tetrodotoxin; D010121:Oxytocin
keywords: Magnocellular neurosecretory cells; Oxytocin; Sodium channel; Supraoptic nucleus; Vasopressin