1. Glycine Induces Migration of Microglial BV-2 Cells via SNAT-Mediated Cell Swelling.
- Author
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Kittl M, Dobias H, Beyreis M, Kiesslich T, Mayr C, Gaisberger M, Ritter M, Kerschbaum HH, and Jakab M
- Subjects
- Amino Acid Transport System A antagonists & inhibitors, Animals, Cell Line, Cell Movement drug effects, Chlorides metabolism, Cyclopentanes pharmacology, Hypotonic Solutions pharmacology, Indans pharmacology, Membrane Potentials drug effects, Mice, Microglia cytology, Microglia metabolism, Nitrobenzoates pharmacology, Patch-Clamp Techniques, Amino Acid Transport System A metabolism, Cell Size drug effects, Glycine pharmacology
- Abstract
Background/aims: The neutral, non-essential amino acid glycine has manifold functions and effects under physiological and pathophysiological conditions. Besides its function as a neurotransmitter in the central nervous system, glycine also exerts immunomodulatory effects and as an osmolyte it participates in cell volume regulation. During phagocytosis, glycine contributes to (local) cell volume-dependent processes like lamellipodium formation. Similar to the expansion of the lamellipodium we assume that glycine also affects the migration of microglial cells in a cell volume-dependent manner., Methods: Mean cell volume (MCV) and cell migration were determined using flow cytometry and trans-well migration assays, respectively. Electrophysiological recordings of the cell membrane potential (Vmem) and swelling-dependent chloride (Cl-) currents (IClswell, VSOR, VRAC) were performed using the whole-cell patch clamp technique., Results: In the murine microglial cell line BV-2, flow cytometry analysis revealed that glycine (5 mM) increases the MCV by ∼9%. The glycine-dependent increase in MCV was suppressed by the partial sodium-dependent neutral amino acid transporter (SNAT) antagonist MeAIB and augmented by the Cl- current blocker DCPIB. Electrophysiological recordings showed that addition of glycine activates a Cl- current under isotonic conditions resembling features of the swelling-activated Cl- current (IClswell). The cell membrane potential (Vmem) displayed a distinctive time course after glycine application; initially, glycine evoked a rapid depolarization mediated by Na+-coupled glycine uptake via SNAT, followed by a further gradual depolarization, which was fully suppressed by DCPIB. Interestingly, glycine significantly increased migration of BV-2 cells, which was suppressed by MeAIB, suggesting that SNAT is involved in the migration process of microglial cells., Conclusion: We conclude that glycine acts as a chemoattractant for microglial cells presumably by a cell volume-dependent mechanism involving SNAT-mediated cell swelling., (© 2018 The Author(s). Published by S. Karger AG, Basel.)
- Published
- 2018
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