Voltage-Gated Sodium Channel Nav1.7 Maintains the Membrane Potential and Regulates Chemokine-Induced Migration of a Subpopulation of Monocyte-Derived Dendritic Cells

Expression of CD1a protein defines two human dendritic cell (DC) subsets with distinct functions. 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 Q-PCR experiments performed on immature sorted CD1a- and CD1a+ DC populations 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. Down-regulation of Nav 1.7 expression accompanying DC maturation is abolished by increasing cytosolic Ca2+ concentration using ionomycin and thapsigargin or inhibiting the NF-κB-pathway. The activity of Nav1.7 results in a depolarized resting potential (−8.7 +/- 1.5 mV) in CD1a+ IDCs as compared to CD1a- cells lacking Nav1.7 (−47 +/- 6.2 mV) or mature DCs used as ¯controls¯ with reduced Nav1.7 expression. Silencing of the SCN9A gene shifted the membrane potential to a hyperpolarizing direction in CD1a+ immature DC resulting in decreased cell migration, similarly to the pharmacological inhibition of Nav1.7 by TTX. The control of IDC function by a voltage-gated sodium channel emerges as a new regulatory mechanism modulating the migration and other responses of these DC subsets.