title: Voltage-gated sodium channel Nav1.7 maintains the membrane potential and regulates the activation and chemokine-induced migration of a monocyte-derived dendritic cell subset.
abstract: Expression of CD1a protein defines a human dendritic cell (DC) subset with unique functional activities. We aimed to study the expression of the Nav1.7 sodium channel and the functional consequences of its activity in CD1a(-) and CD1a(+) DC. Single-cell electrophysiology (patch-clamp) and quantitative PCR experiments performed on sorted CD1a(-) and CD1a(+) immature DC (IDC) showed that the frequency of cells expressing Na(+) current, current density, and the relative expression of the SCN9A gene encoding Nav1.7 were significantly higher in CD1a(+) cells than in their CD1a(-) counterparts. The activity of Nav1.7 results in a depolarized resting membrane potential (-8.7 ± 1.5 mV) in CD1a(+) IDC as compared with CD1a(-) cells lacking Nav1.7 (-47 ± 6.2 mV). Stimulation of DC by inflammatory signals or by increased intracellular Ca(2+) levels resulted in reduced Nav1.7 expression. Silencing of the SCN9A gene shifted the membrane potential to a hyperpolarizing direction in CD1a(+) IDC, resulting in decreased cell migration, whereas pharmacological inhibition of Nav1.7 by tetrodotoxin sensitized the cells for activation signals. Fine-tuning of IDC functions by a voltage-gated sodium channel emerges as a new regulatory mechanism modulating the migration and cytokine responses of these DC subsets.
authors.affiliation: Department of Immunology, Medical and Health Science Center, University of Debrecen, Debrecen, H-4032 Hungary.
authors.forename: Katalin
authors.initials: K
authors.lastname: Kis-Toth
authors.forename: Peter
authors.initials: P
authors.lastname: Hajdu
authors.forename: Ildiko
authors.initials: I
authors.lastname: Bacskai
authors.forename: Orsolya
authors.initials: O
authors.lastname: Szilagyi
authors.forename: Ferenc
authors.initials: F
authors.lastname: Papp
authors.forename: Attila
authors.initials: A
authors.lastname: Szanto
authors.forename: Edit
authors.initials: E
authors.lastname: Posta
authors.forename: Peter
authors.initials: P
authors.lastname: Gogolak
authors.forename: Gyorgy
authors.initials: G
authors.lastname: Panyi
authors.forename: Eva
authors.initials: E
authors.lastname: Rajnavolgyi
mesh_terms: D002454:Cell Differentiation / Q000276:immunology; D002465:Cell Movement / Q000276:immunology*; D002478:Cells, Cultured; D018925:Chemokines / Q000502:physiology*; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D008564:Membrane Potentials / Q000276:immunology*; D009000:Monocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D062556:NAV1.7 Voltage-Gated Sodium Channel; D016192:Resting Phase, Cell Cycle / Q000276:immunology; D015222:Sodium Channels / Q000502:physiology*
chemical_list: D018925:Chemokines; D016207:Cytokines; D062556:NAV1.7 Voltage-Gated Sodium Channel; C486866:SCN9A protein, human; D015222:Sodium Channels