Enhancement of neuronal outward delayed rectifier K+ current by human monocyte-derived macrophages

Dehui Hu, Liu Jianuo, Xiong Huangui

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

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 (IK) and resultant change on neuronal viability in primary rat hippocampal neuronal culture. Bath application of LPS-stimulated MDM-conditioned media (MCM) enhanced neuronal IK in a concentration-dependent manner, whereas non-stimulated MCM failed to alter neuronal IK. The enhancement of neuronal IK was repeated in a macrophage-neuronal co-culture system. The link of stimulated MCM (MCM(+))-associated enhancement of IK 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 IK blocker tetraethylammonium to the culture protected hippocampal neurons from MCM(+)-associated challenge. Further investigation revealed elevated levels of Kv 1.3 and Kv 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 IK and that modulation of Kv channels is a new approach to neuroprotection.

Original languageEnglish (US)
Pages (from-to)1492-1500
Number of pages9
JournalGlia
Volume57
Issue number14
DOIs
StatePublished - 2009

Keywords

  • Hippocampus
  • Neurodegeneration
  • Neuronal culture
  • Voltage-gated K+ channels

ASJC Scopus subject areas

  • Neurology
  • Cellular and Molecular Neuroscience

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