Nicotine inhibits activation of microglial proton currents via interactions with α7 acetylcholine receptors

详细信息    查看全文

• 作者：Mami Noda ; AI Kobayashi
• 关键词：Microglia ; Nicotine ; α7 nAChRs ; Lipopolysaccharide ; NADPH oxidase ; Proton currents
• 刊名：The Journal of Physiological Sciences
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：67
• 期：1
• 页码：235-245
• 全文大小：
• 刊物主题：Human Physiology; Neurosciences; Animal Biochemistry; Animal Physiology; Cell Physiology; Neurobiology;
• 出版者：Springer Japan
• ISSN：1880-6562
• 卷排序：67

文摘

Alpha 7 subunits of nicotinic acetylcholine receptors (nAChRs) are expressed in microglia and are involved in the suppression of neuroinflammation. Over the past decade, many reports show beneficial effects of nicotine, though little is known about the mechanism. Here we show that nicotine inhibits lipopolysaccharide (LPS)-induced proton (H+) currents and morphological change by using primary cultured microglia. The H+ channel currents were measured by whole-cell patch clamp method under voltage-clamp condition. Increased H+ current in activated microglia was attenuated by blocking NADPH oxidase. The inhibitory effect of nicotine was due to the activation of α7 nAChR, not a direct action on the H+ channels, because the effects of nicotine was cancelled by α7 nAChR antagonists. Neurotoxic effect of LPS-activated microglia due to inflammatory cytokines was also attenuated by pre-treatment of microglia with nicotine. These results suggest that α7 nAChRs in microglia may be a therapeutic target in neuroinflammatory diseases.