PMID- 18046732 OWN - NLM STAT- MEDLINE DCOM- 20080314 LR - 20071206 IS - 0894-1491 (Print) IS - 0894-1491 (Linking) VI - 56 IP - 2 DP - 2008 Jan 15 TI - Macrophage attenuation of neuronal excitability: implications for pathogenesis of neurodegenerative disorders. PG - 241-6 AB - Brain macrophages (and microglia) play a crucial role in central nervous system immune and inflammatory responses. They are also critical cells in the pathogenesis of neurodegenerative disorders. To understand how macrophages cause neural cell dysfunction, we investigated the effects of mouse bone marrow-derived macrophages (BMDMs) on rat cortical neuronal physiology in a BMDM-neuronal co-culture system using whole-cell patch clamp techniques. When co-cultured with neuronal cells, BMDMs hyperpolarized the neuronal membrane and attenuated both spontaneous and electrically evoked firings through a decrease in membrane input resistance. The average duration of evoked action potentials (APs) and the latency to fire the APs, in response to a constant depolarizing current injection, were significantly increased by BMDMs. These results indicate that BMDMs attenuate neuronal excitability. Further investigation revealed that BMDMs hyperpolarize neuronal membranes by enhancing neuronal delayed rectifier potassium current (IK), which was blocked by tetraethylammonium. This BMDM-induced attenuation on neuronal excitability may contribute to the pathogenesis of neuronal dysfunction and damage as seen in neurodegenerative disorders. CI - Copyright (c) 2007 Wiley-Liss, Inc. FAU - Wang, Wenwei AU - Wang W AD - Neurophysiology Laboratory, The Center for Neurovirology and Neurodegenerative Disorders, University of Nebraska Medical Center, Omaha, Nebraska 68198-5880, USA. FAU - Hu, Dehui AU - Hu D FAU - Xiong, Huangui AU - Xiong H LA - eng GR - 2 R01 NS041862/NS/NINDS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PL - United States TA - Glia JT - Glia JID - 8806785 SB - IM MH - Animals MH - Bone Marrow Cells/physiology MH - Brain/cytology MH - Cells, Cultured MH - Coculture Techniques/methods MH - Dose-Response Relationship, Radiation MH - Electric Stimulation/methods MH - Embryo, Mammalian MH - Macrophages/chemistry/*physiology MH - Male MH - Membrane Potentials/*physiology MH - Mice MH - Mice, Inbred C57BL MH - Neurons/*physiology MH - Patch-Clamp Techniques/methods MH - Rats MH - Rats, Sprague-Dawley EDAT- 2007/11/30 09:00 MHDA- 2008/03/15 09:00 CRDT- 2007/11/30 09:00 PHST- 2007/11/30 09:00 [pubmed] PHST- 2008/03/15 09:00 [medline] PHST- 2007/11/30 09:00 [entrez] AID - 10.1002/glia.20609 [doi] PST - ppublish SO - Glia. 2008 Jan 15;56(2):241-6. doi: 10.1002/glia.20609.