Acid- and Volume-Sensitive Chloride Currents in Microglial Cells. 2019

Michael Kittl, and Katharina Helm, and Marlena Beyreis, and Christian Mayr, and Martin Gaisberger, and Martina Winklmayr, and Markus Ritter, and Martin Jakab
Institute of Physiology and Pathophysiology, Paracelsus Medical University, 5020 Salzburg, Austria.

Many cell types express an acid-sensitive outwardly rectifying (ASOR) anion current of an unknown function. We characterized such a current in BV-2 microglial cells and then studied its interrelation with the volume-sensitive outwardly rectifying (VSOR) Cl- current and the effect of acidosis on cell volume regulation. We used patch clamp, the Coulter method, and the pH-sensitive dye BCECF to measure Cl- currents and cell membrane potentials, mean cell volume, and intracellular pH, respectively. The ASOR current activated at pH ≤ 5.0 and displayed an I- > Cl- > gluconate- permeability sequence. When compared to the VSOR current, it was similarly sensitive to DIDS, but less sensitive to DCPIB, and insensitive to tamoxifen. Under acidic conditions, the ASOR current was the dominating Cl- conductance, while the VSOR current was apparently inactivated. Acidification caused cell swelling under isotonic conditions and prevented the regulatory volume decrease under hypotonicity. We conclude that acidification, associated with activation of the ASOR- and inactivation of the VSOR current, massively impairs cell volume homeostasis. ASOR current activation could affect microglial function under acidotoxic conditions, since acidosis is a hallmark of pathophysiological events like inflammation, stroke or ischemia and migration and phagocytosis in microglial cells are closely related to cell volume regulation.

UI MeSH Term Description Entries
D007455 Iodine A nonmetallic element of the halogen group that is represented by the atomic symbol I, atomic number 53, and atomic weight of 126.90. It is a nutritionally essential element, especially important in thyroid hormone synthesis. In solution, it has anti-infective properties and is used topically. Iodine-127,Iodine 127
D009997 Osmotic Pressure The pressure required to prevent the passage of solvent through a semipermeable membrane that separates a pure solvent from a solution of the solvent and solute or that separates different concentrations of a solution. It is proportional to the osmolality of the solution. Osmotic Shock,Hypertonic Shock,Hypertonic Stress,Hypotonic Shock,Hypotonic Stress,Osmotic Stress,Hypertonic Shocks,Hypertonic Stresses,Hypotonic Shocks,Hypotonic Stresses,Osmotic Pressures,Osmotic Shocks,Osmotic Stresses,Pressure, Osmotic,Pressures, Osmotic,Shock, Hypertonic,Shock, Hypotonic,Shock, Osmotic,Shocks, Hypertonic,Shocks, Hypotonic,Shocks, Osmotic,Stress, Hypertonic,Stress, Hypotonic,Stress, Osmotic,Stresses, Hypertonic,Stresses, Hypotonic,Stresses, Osmotic
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D002712 Chlorides Inorganic compounds derived from hydrochloric acid that contain the Cl- ion. Chloride,Chloride Ion Level,Ion Level, Chloride,Level, Chloride Ion
D006863 Hydrogen-Ion Concentration The normality of a solution with respect to HYDROGEN ions; H+. It is related to acidity measurements in most cases by pH pH,Concentration, Hydrogen-Ion,Concentrations, Hydrogen-Ion,Hydrogen Ion Concentration,Hydrogen-Ion Concentrations
D000200 Action Potentials Abrupt changes in the membrane potential that sweep along the CELL MEMBRANE of excitable cells in response to excitation stimuli. Spike Potentials,Nerve Impulses,Action Potential,Impulse, Nerve,Impulses, Nerve,Nerve Impulse,Potential, Action,Potential, Spike,Potentials, Action,Potentials, Spike,Spike Potential
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D017136 Ion Transport The movement of ions across energy-transducing cell membranes. Transport can be active, passive or facilitated. Ions may travel by themselves (uniport), or as a group of two or more ions in the same (symport) or opposite (antiport) directions. Antiport,Ion Cotransport,Ion Exchange, Intracellular,Symport,Uniport,Active Ion Transport,Facilitated Ion Transport,Passive Ion Transport,Cotransport, Ion,Exchange, Intracellular Ion,Intracellular Ion Exchange,Ion Transport, Active,Ion Transport, Facilitated,Ion Transport, Passive,Transport, Active Ion,Transport, Ion
D017628 Microglia The third type of glial cell, along with astrocytes and oligodendrocytes (which together form the macroglia). Microglia vary in appearance depending on developmental stage, functional state, and anatomical location; subtype terms include ramified, perivascular, ameboid, resting, and activated. Microglia clearly are capable of phagocytosis and play an important role in a wide spectrum of neuropathologies. They have also been suggested to act in several other roles including in secretion (e.g., of cytokines and neural growth factors), in immunological processing (e.g., antigen presentation), and in central nervous system development and remodeling. Microglial Cell,Cell, Microglial,Microglial Cells,Microglias
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus

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