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Physiological mechanisms of lysophosphatidylcholine‐induced de‐ramification of murine microglia
Author(s) -
Schilling Tom,
Lehmann Frank,
Rückert Berit,
Eder Claudia
Publication year - 2004
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.2004.060632
Subject(s) - biophysics , chemistry , lysophosphatidylcholine , divalent , charybdotoxin , membrane potential , dids , depolarization , bumetanide , cotransporter , patch clamp , hyperpolarization (physics) , extracellular , reversal potential , ion transporter , biochemistry , stereochemistry , biology , membrane , sodium , receptor , phospholipid , organic chemistry , phosphatidylcholine , nuclear magnetic resonance spectroscopy
Activation of microglial cells, the resident macrophages of the brain, occurs rapidly following brain injury. De‐ramification, i.e. transformation from ramified into amoeboid morphology is one of the earliest manifestations of microglial activation. In the present study, we identified the physiological mechanisms underlying microglial de‐ramification induced by lysophosphatidylcholine (LPC). Patch‐clamp experiments revealed activation of non‐selective cation currents and Ca 2+ ‐dependent K + currents by extracellular LPC. LPC‐activated non‐selective cation channels were permeable for monovalent and divalent cations. They were inhibited by Gd 3+ , La 3+ , Zn 2+ and Grammostola spatulata venom, but were unaffected by diltiazem, LOE908MS, amiloride and DIDS. Ca 2+ influx through non‐selective cation channels caused sustained increases in intracellular Ca 2+ concentration. These Ca 2+ increases were sufficient to elicit charybdotoxin‐sensitive Ca 2+ ‐dependent K + currents. However, increased [Ca 2+ ] i was not required for LPC‐induced morphological changes. In LPC‐stimulated microglial cells, non‐selective cation currents caused transient membrane depolarization, which was followed by sustained membrane hyperpolarization induced by Ca 2+ ‐dependent K + currents. Furthermore, LPC elicited K + efflux by stimulating electroneutral K + –Cl − cotransporters, which were inhibited by furosemide and DIOA. LPC‐induced microglial de‐ramification was prevented by simultaneous inhibition of non‐selective cation channels and K + –Cl − cotransporters, suggesting their functional importance for microglial activation.