PMID- 22572846 OWN - NLM STAT- MEDLINE DCOM- 20121001 LR - 20200930 IS - 1522-1563 (Electronic) IS - 0363-6143 (Linking) VI - 303 IP - 2 DP - 2012 Jul 15 TI - Lipopolysaccharide-sensitive H+ current in dendritic cells. PG - C204-12 LID - 10.1152/ajpcell.00059.2012 [doi] AB - Dendritic cells (DCs) are the most potent antigen-presenting cells equipped to transport antigens from the periphery to lymphoid tissues and to present them to T cells. Ligation of Toll-like receptor 4 (TLR4), expressed on the DC surface, by lipopolysaccharides (LPS), elements of the Gram-negative bacteria outer wall, induces DC maturation. Initial steps of maturation include stimulation of antigen endocytosis and enhanced reactive oxygen species (ROS) production with eventual downregulation of endocytic capacity in fully matured DCs. ROS production depends on NADPH oxidase (NOX2), the activity of which requires continuous pH and charge compensation. The present study demonstrates, for the first time, the functional expression of voltage-gated proton (Hv1) channels in mouse bone marrow-derived DCs. In whole cell patch-clamp experiments, we recorded Zn(2+) (50 muM)-sensitive outwardly rectifying currents activated upon depolarization, which were highly selective for H(+), with the reversal potential shift of 38 mV per pH unit. The threshold voltage of activation (V(threshold)) was dependent on the pH gradient and was close to the empirically predicted V(threshold) for the Hv1 currents. LPS (1 mug/ml) had bimodal effects on Hv1 channels: acute LPS treatment increased Hv1 channel activity, whereas 24 h of LPS incubation significantly inhibited Hv1 currents and decreased ROS production. Activation of H(+) currents by acute application of LPS was abolished by PKC inhibitor GFX (10 nM). According to electron current measurements, acute LPS application was associated with increased NOX2 activity. FAU - Szteyn, Kalina AU - Szteyn K AD - Department of Physiology, University of Tubingen, Germany. FAU - Yang, Wenting AU - Yang W FAU - Schmid, Evi AU - Schmid E FAU - Lang, Florian AU - Lang F FAU - Shumilina, Ekaterina AU - Shumilina E LA - eng PT - Journal Article DEP - 20120509 PL - United States TA - Am J Physiol Cell Physiol JT - American journal of physiology. Cell physiology JID - 100901225 RN - 0 (Hv1 proton channel, mouse) RN - 0 (Ion Channels) RN - 0 (Lipopolysaccharides) RN - 0 (Reactive Oxygen Species) SB - IM MH - Animals MH - Cells, Cultured MH - Dendritic Cells/drug effects/*metabolism MH - Hydrogen-Ion Concentration MH - Ion Channels/*biosynthesis MH - Lipopolysaccharides/*pharmacology MH - Mice MH - Mice, 129 Strain MH - Mice, Inbred C57BL MH - Reactive Oxygen Species/metabolism EDAT- 2012/05/11 06:00 MHDA- 2012/10/02 06:00 CRDT- 2012/05/11 06:00 PHST- 2012/05/11 06:00 [entrez] PHST- 2012/05/11 06:00 [pubmed] PHST- 2012/10/02 06:00 [medline] AID - ajpcell.00059.2012 [pii] AID - 10.1152/ajpcell.00059.2012 [doi] PST - ppublish SO - Am J Physiol Cell Physiol. 2012 Jul 15;303(2):C204-12. doi: 10.1152/ajpcell.00059.2012. Epub 2012 May 9.