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Effects of general anesthetics on P2X4 receptors in a mouse microglial cell line

Hasaka, Megumia; Mori, Takashia; Matsuura, Tadashia; Narahashi, Toshioc; Kuno, Miyukib; Asada, Akiraa; Nishikawa, Kiyonobua

doi: 10.1097/WNR.0b013e32835509db
Glial Cells

The purinergic P2X4 receptors (P2X4Rs) of spinal microglia are upregulated after a peripheral nerve injury and play important roles in the pathogenesis of chronic pain. The effects of general anesthetics on chronic pain and the mechanisms are still unclear. The aim of this study is to examine the effects of general anesthetics on microglial P2X4Rs. Currents induced by ATP were recorded by the whole-cell clamp technique using a mouse microglial cell line (MG5). Isoflurane and sevoflurane, ketamine, thiopental, midazolam, and propofol were coapplied with ATP using the U-tube system or added to the external perfusate. ATP-induced two distinct types of current: P2X4R-mediated and P2X7R-mediated currents. P2X4R-mediated currents were identified pharmacologically and isolated. Volatile anesthetics including sevoflurane and isoflurane and intravenous anesthetics including thiopental, ketamine, and midazolam had no effect at clinically relevant concentrations (n=5–8). Propofol showed a dual effect, potentiating at lower concentrations (0.3–3 µM) and inhibiting at higher concentrations (IC50 57 µM). The maximum enhancement was observed at 1 µM propofol (143±5% of control, n=5). Propofol (1 µM) shifted the dose–response curve for the P2X4R currents to lower concentrations of ATP and increased the maximum amplitude. Propofol exerted dual actions on P2X4R-mediated currents at clinically relevant concentrations. This may suggest that the administration of propofol could affect the development of chronic pain through the modulation of microglial P2X4R responses.

Departments of aAnesthesiology

bPhysiology, Osaka City University Graduate School of Medicine, Osaka, Japan

cDepartment of Molecular Pharmacology and Biological Chemistry, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA

Correspondence to Takashi Mori, MD, PhD, Department of Anesthesiology, Osaka City University Graduate School of Medicine, 1-5-7 Asahi-machi, Abeno-ku, Osaka 545-8586, Japan Tel: +81 666 452 186; fax: +81 666 452 489; e-mail: m1377033@med.osaka-cu.ac.jp

Received March 13, 2012

Accepted April 19, 2012

© 2012 Lippincott Williams & Wilkins, Inc.