title: Enhancement of neuronal outward delayed rectifier K+ current by human monocyte-derived macrophages.
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 (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-dependent manner, 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.
authors.affiliation: Neurophysiology Laboratory, Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, Nebraska 68198-5880, USA.
authors.forename: Dehui
authors.initials: D
authors.lastname: Hu
authors.forename: Jianuo
authors.initials: J
authors.lastname: Liu
authors.forename: Huangui
authors.initials: H
authors.lastname: Xiong
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D018920:Coculture Techniques; D051668:Delayed Rectifier Potassium Channels / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D051664:Kv1.3 Potassium Channel / Q000378:metabolism; D051666:Kv1.5 Potassium Channel / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity; D008264:Macrophages / Q000187:drug effects / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009000:Monocytes / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D011188:Potassium / Q000378:metabolism; D026902:Potassium Channel Blockers / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D019789:Tetraethylammonium / Q000494:pharmacology
chemical_list: D051668:Delayed Rectifier Potassium Channels; D051664:Kv1.3 Potassium Channel; D051666:Kv1.5 Potassium Channel; D008070:Lipopolysaccharides; D026902:Potassium Channel Blockers; D019789:Tetraethylammonium; D011188:Potassium