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Article

Acid- and Volume-Sensitive Chloride Currents in Microglial Cells

by
Michael Kittl
1,2,
Katharina Helm
1,
Marlena Beyreis
1,
Christian Mayr
1,
Martin Gaisberger
1,3,4,
Martina Winklmayr
1,3,
Markus Ritter
1,3,† and
Martin Jakab
1,*,†
1
Institute of Physiology and Pathophysiology, Paracelsus Medical University, 5020 Salzburg, Austria
2
Department of Biosciences, University of Salzburg, 5020 Salzburg, Austria
3
Ludwig Boltzmann Institute for Arthritis and Rehabilitation, Paracelsus Medical University, 5020 Salzburg, Austria
4
Gastein Research Institute, Paracelsus Medical University, 5020 Salzburg, Austria
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Int. J. Mol. Sci. 2019, 20(14), 3475; https://doi.org/10.3390/ijms20143475
Submission received: 19 June 2019 / Revised: 11 July 2019 / Accepted: 12 July 2019 / Published: 15 July 2019
(This article belongs to the Special Issue Ion Transporters and Channels in Physiology and Pathophysiology 2.0: from Molecules to Whole Bodies)
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Abstract

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.
Keywords: acidic; anion; chloride; Cl− current; microglia; pH; RVD; swelling-activated; volume regulation acidic; anion; chloride; Cl− current; microglia; pH; RVD; swelling-activated; volume regulation

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MDPI and ACS Style

Kittl, M.; Helm, K.; Beyreis, M.; Mayr, C.; Gaisberger, M.; Winklmayr, M.; Ritter, M.; Jakab, M. Acid- and Volume-Sensitive Chloride Currents in Microglial Cells. Int. J. Mol. Sci. 2019, 20, 3475. https://doi.org/10.3390/ijms20143475

AMA Style

Kittl M, Helm K, Beyreis M, Mayr C, Gaisberger M, Winklmayr M, Ritter M, Jakab M. Acid- and Volume-Sensitive Chloride Currents in Microglial Cells. International Journal of Molecular Sciences. 2019; 20(14):3475. https://doi.org/10.3390/ijms20143475

Chicago/Turabian Style

Kittl, Michael, Katharina Helm, Marlena Beyreis, Christian Mayr, Martin Gaisberger, Martina Winklmayr, Markus Ritter, and Martin Jakab. 2019. "Acid- and Volume-Sensitive Chloride Currents in Microglial Cells" International Journal of Molecular Sciences 20, no. 14: 3475. https://doi.org/10.3390/ijms20143475

APA Style

Kittl, M., Helm, K., Beyreis, M., Mayr, C., Gaisberger, M., Winklmayr, M., Ritter, M., & Jakab, M. (2019). Acid- and Volume-Sensitive Chloride Currents in Microglial Cells. International Journal of Molecular Sciences, 20(14), 3475. https://doi.org/10.3390/ijms20143475

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