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Acute actions of tumor necrosis factor-alpha on intracellular Ca(2+) and K(+) currents in human microglia.

Authors
McLarnon, JG; Franciosi, S; Wang, X; Bae, JH; Choi, HB; Kim, SU
Citation
Neuroscience, 104(4):1175-1184, 2001
Journal Title
Neuroscience
ISSN
0306-45221873-7544
Abstract
The effects of acute application of the pro-inflammatory cytokine tumor necrosis factor-alpha (TNFalpha) on levels of intracellular Ca(2+) ([Ca(2+)]i) and on whole-cell outward and inward K(+) currents were studied in cultured human microglia. TNFalpha elicited a linear increase in [Ca(2+)]i to a plateau level in microglia bathed in either standard physiological saline solution or Ca(2+)-free physiological saline solution. The rate of increase of [Ca(2+)]i or the level of [Ca(2+)]i attained was not significantly altered in the absence of external Ca(2+) indicating that Ca(2+) influx did not contribute appreciably to the cytokine-induced rise in [Ca(2+)]i. This point was directly confirmed using Mn(2+) quenching where no change in signal fluorescence was observed with TNFalpha treatment of microglia in Ca(2+)-free physiological saline solution. The rate of increase of [Ca(2+)]i induced by TNFalpha in Ca(2+)-free physiological saline solution was not altered by prior application of ATP to deplete inositol triphosphate stores indicating that these stores did not contribute to the cytokine response. In whole-cell patch clamp recordings, the acute treatment of human microglia with TNFalpha led to the expression of an outward K(+) current in one-third (14 of 41) of cells. This current was activated at potentials positive to -30 mV, showed rapid kinetics of activation with no evident inactivation and had an I-V relation exhibiting outward rectification. Analysis of tail currents showed reversal of the outward K(+) current near -70 mV and tetraethylammonium (10 mM) inhibited the outward K(+) current to 24% of control level. Acute application of TNFalpha had no effect to alter inward rectifier currents generated from voltage ramps. The signaling pathways involving TNFalpha modulation of [Ca(2+)]i and K(+) channels in human microglia may contribute to functional and pathological actions of the cytokine in the brain.
MeSH terms
Adenosine Triphosphate/metabolismAdenosine Triphosphate/pharmacologyBrain/cytologyBrain/metabolismBrain/physiopathologyCalcium/deficiencyCalcium Channels/drug effects*Calcium Channels/metabolismCalcium Signaling/drug effects*Calcium Signaling/physiologyCells, Cultured/drug effectsCells, Cultured/metabolismDose-Response Relationship, DrugEncephalitis/metabolism*Encephalitis/physiopathologyEnzyme Inhibitors/pharmacologyFetusHumansIndoles/pharmacologyIntracellular Fluid/drug effects*Intracellular Fluid/metabolismManganese/pharmacologyMembrane Potentials/drug effectsMembrane Potentials/physiologyMicroglia/drug effects*Microglia/metabolismMicroscopy, FluorescencePatch-Clamp TechniquesPotassium Channels/drug effects*Potassium Channels/metabolismSignal Transduction/drug effectsSignal Transduction/physiologySpectrometry, FluorescenceTetraethylammonium/pharmacologyTumor Necrosis Factor-alpha/pharmacology*
PMID
11457600
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Neurology
AJOU Authors
김, 승업
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