Present address: Department of Physiology, School of Basic Medical Sciences, The Southern Medical University, Guangzhou, 510515, China.
Involvement of the 4-aminopyridine-sensitive transient A-type K+ current in macrophage-induced neuronal injury
Article first published online: 13 JAN 2010
© The Authors (2010). Journal Compilation © Federation of European Neuroscience Societies and Blackwell Publishing Ltd
European Journal of Neuroscience
Volume 31, Issue 2, pages 214–222, January 2010
How to Cite
Hu, D., Liu, J., Keblesh, J. and Xiong, H. (2010), Involvement of the 4-aminopyridine-sensitive transient A-type K+ current in macrophage-induced neuronal injury. European Journal of Neuroscience, 31: 214–222. doi: 10.1111/j.1460-9568.2009.07063.x
- Issue published online: 18 JAN 2010
- Article first published online: 13 JAN 2010
- Received 30 July 2009, accepted 13 November 2009
- potassium channels
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 (IA) and resultant neuronal injury in primary rat hippocampal neuronal cultures. Bath application of LPS-stimulated MDM-conditioned media (MCM+) enhanced neuronal IA in a concentration-dependent manner. Non-stimulated MCM (MCM-) failed to alter IA. The enhancement of neuronal IA was recapitulated in neurons co-cultured with macrophages. The link of MCM(+)-induced enhancement of IA 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 IA 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 IA. These results suggest that during brain inflammation macrophages (and microglia) might mediate neuronal injury via enhancement of neuronal IA, and that neuronal Kv 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.