Nicotine inhibits activation of microglial proton currents via interactions with alpha 7 acetylcholine receptors

作者：Noda Mami^*; Kobayashi A I

来源：Journal of Physiological Sciences, 2017, 67(1): 235-245.

DOI：10.1007/s12576-016-0460-5

• Microglia
• Nicotine
• alpha 7 nAChRs
• Lipopolysaccharide
• NADPH oxidase
• Proton currents

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 alpha 7 nAChR, not a direct action on the H+ channels, because the effects of nicotine was cancelled by alpha 7 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 alpha 7 nAChRs in microglia may be a therapeutic target in neuroinflammatory diseases.

• 出版日期2017-1