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Enhancement of neuronal outward delayed rectifier K+ current by human monocyte‐derived macrophages
Author(s) -
Hu Dehui,
Liu Jianuo,
Xiong Huangui
Publication year - 2009
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.20865
Subject(s) - neuroprotection , premovement neuronal activity , dapi , biology , hippocampal formation , tetraethylammonium , propidium iodide , microbiology and biotechnology , neuroscience , potassium channel blocker , potassium channel , apoptosis , programmed cell death , chemistry , endocrinology , biochemistry , potassium , organic chemistry
Macrophages are critical cells in mediating the pathology of neurodegenerative disorders and enhancement of neuronal outward potassium (K + ) current has implicated in neuronal apoptosis. To understand how activated macrophages induce neuronal dysfunction and injury, we studied the effects of lipopolysaccharide (LPS)‐stimulated human monocytes‐derived macrophage (MDM) on neuronal outward delayed rectifier K + current ( I K ) and resultant change on neuronal viability in primary rat hippocampal neuronal culture. Bath application of LPS‐stimulated MDM‐conditioned media (MCM) enhanced neuronal I K in a concentration‐dependentmanner, whereas non‐stimulated MCM failed to alter neuronal I K . The enhancement of neuronal I K was repeated in a macrophage‐neuronal co‐culture system. The link of stimulated MCM (MCM(+))‐associated enhancement of I K to MCM(+)‐induced neuronal injury, as detected by PI/DAPI (propidium iodide/4′,6‐diamidino‐2‐phenylindol) staining and MTT assay, was demonstrated by experimental results showing that addition of I K blocker tetraethylammonium to the culture protected hippocampal neurons from MCM(+)‐associated challenge. Further investigation revealed elevated levels of K v 1.3 and K v 1.5 channel expression in hippocampal neurons after addition of MCM(+) to the culture. These results suggest that during brain inflammation macrophages, through their capacity of releasing bioactive molecules, induce neuronal injury by enhancing neuronal I K and that modulation of K v channels is a new approach to neuroprotection. © 2009 Wiley‐Liss, Inc.