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Non-essential contribution of LRRC8A to volume regulation

  • Ion channels, receptors and transporters
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Abstract

Volume regulation is an essential property of any living cell and needs to be tightly controlled. While different types of K+ channels have been found to participate in the regulation of cell volume, the newly identified volume-regulated anion channel (VRAC) LRRC8 has been claimed to be essential for volume regulation. In unbiased genome-wide small interfering RNA (siRNA) screens, two independent studies identified LRRC8A/Swell1 as an essential component of VRAC, thus being indispensable for cellular volume regulation. We reanalyzed the role of LRRC8A for VRAC and regulatory volume decrease (RVD) in several cell types and under various conditions. While the role of LRRC8A for VRAC and its contribution to RVD is confirmed, we find that it is not essential for swelling-activated anion currents or cellular volume regulation, or apoptotic cell shrinkage. The contribution of LRRC8A is variable and largely depending on the cell type.

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Acknowledgments

This study was supported by DFG SFB699-A7/A12, DFG KU756/12-1, and Volkswagenstiftung AZ 87 499. HeLa cells stably expressing halide-sensitive YFP-H148Q/I152L were generously provided by Prof. Dr. M. Amaral, University of Lisbon, Portugal. HCT-wt (LRRC8A+/+) and HCT-LRRC8A−/− cells were from Dr. Voss/Prof. Dr. Jentsch (FMP, Berlin). pIRES2 LRRC8A-T44C was a generous gift from Dr. Zhaozhu Qiu (The Scripps Research Institute, La Jolla, USA). The excellent technical assistance by Mss. B. Wild, P. Seeberger, and E. Tartler is gratefully acknowledged.

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Authors and Affiliations

  1. Institut für Physiologie, Universität Regensburg, Universitätsstraße 31, 93053, Regensburg, Germany

    Lalida Sirianant, Podchanart Wanitchakool, Jiraporn Ousingsawat, Roberta Benedetto, Anna Zormpa, Ines Cabrita, Rainer Schreiber & Karl Kunzelmann

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  1. Lalida Sirianant
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  2. Podchanart Wanitchakool
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  3. Jiraporn Ousingsawat
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  8. Karl Kunzelmann
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Correspondence to Karl Kunzelmann.

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Sirianant, L., Wanitchakool, P., Ousingsawat, J. et al. Non-essential contribution of LRRC8A to volume regulation. Pflugers Arch - Eur J Physiol 468, 805–816 (2016). https://doi.org/10.1007/s00424-016-1789-6

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  • DOI: https://doi.org/10.1007/s00424-016-1789-6

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