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Inhibition of voltage‐gated proton channels by local anaesthetics in GMI‐R1 rat microglia
Author(s) -
Matsuura Tadashi,
Mori Takashi,
Hasaka Megumi,
Kuno Miyuki,
Kawawaki Junko,
Nishikawa Kiyonobu,
Narahashi Toshio,
Sawada Makoto,
Asada Akira
Publication year - 2012
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2011.218149
Subject(s) - bupivacaine , lidocaine , microglia , phagocytosis , chemistry , immune system , intracellular , pharmacology , infiltration (hvac) , biophysics , anesthesia , neuroscience , microbiology and biotechnology , medicine , inflammation , biology , immunology , biochemistry , materials science , composite material
Non‐technical summary Lidocaine and bupivacaine are the most commonly used local anaesthetics in clinical practices such as neuraxial anaesthesia and local infiltration. They are known to suppress phagocytosis and the production of reactive oxygen species in immune cells. Voltage‐gated proton channels are abundantly expressed in immune cells, including microglia, and play crucial roles in sustaining phagocytosis. We show that both lidocaine and bupivacaine increase the intracellular pH of microglia by their weak base properties and, consequently, inhibit proton channels. This is a novel mechanism underlying actions of local anaesthetics. Our results also indicate that the proton channel is a useful tool for monitoring the behaviours of lidocaine and bupivacaine across the cellular membrane.