title: Developmental switch of the expression of ion channels in human dendritic cells.
abstract: Modulation of the expression and activity of plasma membrane ion channels is one of the mechanisms by which immune cells can regulate their intracellular Ca(2+) signaling pathways required for proliferation and/or differentiation. Voltage-gated K+ channels, inwardly rectifying K+ channels, and Ca(2+)-activated K+ channels have been described to play a major role in controlling the membrane potential in lymphocytes and professional APCs, such as monocytes, macrophages, and dendritic cells (DCs). Our study aimed at the characterization and identification of ion channels expressed in the course of human DC differentiation from monocytes. We report in this study for the first time that immature monocyte-derived DCs express voltage-gated Na+ channels in their plasma membrane. The analysis of the biophysical and pharmacological properties of the current and PCR-based cloning revealed the presence of Nav1.7 channels in immature DCs. Transition from the immature to a mature differentiation state, however, was accompanied by the down-regulation of Nav1.7 expression concomitant with the up-regulation of voltage-gated Kv1.3 K+ channel expression. The presence of Kv1.3 channels seems to be common for immune cells; hence, selective Kv1.3 blockers may emerge as candidates for inhibiting various functions of mature DCs that involve their migratory, cytokine-secreting, and T cell-activating potential.
authors.affiliation: Department of Biophysics and Cell Biology, University of Debrecen, Debrecen 4012, Hungary.
authors.forename: Emese
authors.initials: E
authors.lastname: Zsiros
authors.forename: Katalin
authors.initials: K
authors.lastname: Kis-Toth
authors.forename: Peter
authors.initials: P
authors.lastname: Hajdu
authors.forename: Rezso
authors.initials: R
authors.lastname: Gaspar
authors.forename: Joanna
authors.initials: J
authors.lastname: Bielanska
authors.forename: Antonio
authors.initials: A
authors.lastname: Felipe
authors.forename: Eva
authors.initials: E
authors.lastname: Rajnavolgyi
authors.forename: Gyorgy
authors.initials: G
authors.lastname: Panyi
mesh_terms: D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D002460:Cell Line; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology; D018507:Gene Expression Regulation, Developmental / Q000276:immunology*; D006801:Humans; D016130:Immunophenotyping; D015640:Ion Channel Gating / Q000235:genetics / Q000276:immunology; D051664:Kv1.3 Potassium Channel / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D009000:Monocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D062556:NAV1.7 Voltage-Gated Sodium Channel; D018408:Patch-Clamp Techniques; D026941:Sodium Channel Blockers / Q000494:pharmacology; D015222:Sodium Channels / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D013779:Tetrodotoxin / Q000494:pharmacology; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology
chemical_list: D051664:Kv1.3 Potassium Channel; D062556:NAV1.7 Voltage-Gated Sodium Channel; C486866:SCN9A protein, human; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D013779:Tetrodotoxin