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

Katalin Kis-Toth, Peter Hajdu, Ildiko Bacskai, Orsolya Szilagyi, Ferenc Papp, Attila Szanto, Edit Posta, P. Gogolák, G. Panyi, E. Rajnavolgyi

Research output: Contribution to journalArticle

24 Citations (Scopus)

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 Ca2+ 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.

Original languageEnglish
Pages (from-to)1273-1280
Number of pages8
JournalJournal of Immunology
Volume187
Issue number3
DOIs
Publication statusPublished - Aug 1 2011

Fingerprint

NAV1.7 Voltage-Gated Sodium Channel
Chemokines
Membrane Potentials
Dendritic Cells
Monocytes
Voltage-Gated Sodium Channels
Specific Gravity
Sodium Channels
Electrophysiology
Tetrodotoxin
Gene Silencing
Cell Movement
Pharmacology
Cytokines
Gene Expression
Polymerase Chain Reaction

ASJC Scopus subject areas

  • Immunology

Cite this

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. / Kis-Toth, Katalin; Hajdu, Peter; Bacskai, Ildiko; Szilagyi, Orsolya; Papp, Ferenc; Szanto, Attila; Posta, Edit; Gogolák, P.; Panyi, G.; Rajnavolgyi, E.

In: Journal of Immunology, Vol. 187, No. 3, 01.08.2011, p. 1273-1280.

Research output: Contribution to journalArticle

Kis-Toth, Katalin ; Hajdu, Peter ; Bacskai, Ildiko ; Szilagyi, Orsolya ; Papp, Ferenc ; Szanto, Attila ; Posta, Edit ; Gogolák, P. ; Panyi, G. ; Rajnavolgyi, E. / 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. In: Journal of Immunology. 2011 ; Vol. 187, No. 3. pp. 1273-1280.
@article{2684dc6fc5bb47cdad1db1e2cd451982,
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 Ca2+ 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.",
author = "Katalin Kis-Toth and Peter Hajdu and Ildiko Bacskai and Orsolya Szilagyi and Ferenc Papp and Attila Szanto and Edit Posta and P. Gogol{\'a}k and G. Panyi and E. Rajnavolgyi",
year = "2011",
month = "8",
day = "1",
doi = "10.4049/jimmunol.1003345",
language = "English",
volume = "187",
pages = "1273--1280",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "3",

}

TY - JOUR

T1 - 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

AU - Kis-Toth, Katalin

AU - Hajdu, Peter

AU - Bacskai, Ildiko

AU - Szilagyi, Orsolya

AU - Papp, Ferenc

AU - Szanto, Attila

AU - Posta, Edit

AU - Gogolák, P.

AU - Panyi, G.

AU - Rajnavolgyi, E.

PY - 2011/8/1

Y1 - 2011/8/1

N2 - 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 Ca2+ 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.

AB - 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 Ca2+ 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.

UR - http://www.scopus.com/inward/record.url?scp=80051621439&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80051621439&partnerID=8YFLogxK

U2 - 10.4049/jimmunol.1003345

DO - 10.4049/jimmunol.1003345

M3 - Article

VL - 187

SP - 1273

EP - 1280

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 3

ER -