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Involvement of the 4‐aminopyridine‐sensitive transient A‐type K + current in macrophage‐induced neuronal injury
Author(s) -
Hu Dehui,
Liu Jianuo,
Keblesh James,
Xiong Huangui
Publication year - 2010
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.2009.07063.x
Subject(s) - microglia , premovement neuronal activity , dapi , hippocampal formation , lipopolysaccharide , chemistry , microbiology and biotechnology , glutamate receptor , neuroscience , macrophage , immune system , inflammation , biology , immunology , in vitro , biochemistry , apoptosis , receptor
Through their capacity to secrete, upon activation, a variety of bioactive molecules, brain macrophages (and resident microglia) play an important role in brain immune and inflammatory responses. To test our hypothesis that activated macrophages induce neuronal injury by enhancing neuronal outward K + current, we studied the effects of lipopolysaccharide (LPS)‐stimulated human monocyte‐derived macrophage (MDM) on neuronal transient A‐type K + current ( I A ) and resultant neuronal injury in primary rat hippocampal neuronal cultures. Bath application of LPS‐stimulated MDM‐conditioned media (MCM+) enhanced neuronal I A in a concentration‐dependent manner. Non‐stimulated MCM (MCM‐) failed to alter I A . The enhancement of neuronal I A was recapitulated in neurons co‐cultured with macrophages. The link of MCM(+)‐induced enhancement of I A to MCM(+)‐associated neuronal injury, as detected by propidium iodide and 4″,6‐diamidino‐2‐phenylindol staining (DAPI) and 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl tetrazolium bromide (MTT) assay, was demonstrated by experimental results showing that addition of I A blocker 4‐aminopyridine to the cultures protected hippocampal neurons from MCM(+)‐induced neuronal injury. Further investigation revealed that glutamate was involved in MCM(+)‐induced enhancement of neuronal I A . These results suggest that during brain inflammation macrophages (and microglia) might mediate neuronal injury via enhancement of neuronal I A , and that neuronal K v channel might be a potential target for the development of therapeutic strategies for some neurodegenerative disorders by which immune and inflammatory responses are believed to be involved in the pathogenesis.