title: Non-essential contribution of LRRC8A to volume regulation.
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.
authors.affiliation: Institut für Physiologie, Universität Regensburg, Universitätsstraße 31, 93053, Regensburg, Germany.
authors.forename: Lalida
authors.initials: L
authors.lastname: Sirianant
authors.affiliation: Institut für Physiologie, Universität Regensburg, Universitätsstraße 31, 93053, Regensburg, Germany.
authors.forename: Podchanart
authors.initials: P
authors.lastname: Wanitchakool
authors.affiliation: Institut für Physiologie, Universität Regensburg, Universitätsstraße 31, 93053, Regensburg, Germany.
authors.forename: Jiraporn
authors.initials: J
authors.lastname: Ousingsawat
authors.affiliation: Institut für Physiologie, Universität Regensburg, Universitätsstraße 31, 93053, Regensburg, Germany.
authors.forename: Roberta
authors.initials: R
authors.lastname: Benedetto
authors.affiliation: Institut für Physiologie, Universität Regensburg, Universitätsstraße 31, 93053, Regensburg, Germany.
authors.forename: Anna
authors.initials: A
authors.lastname: Zormpa
authors.affiliation: Institut für Physiologie, Universität Regensburg, Universitätsstraße 31, 93053, Regensburg, Germany.
authors.forename: Ines
authors.initials: I
authors.lastname: Cabrita
authors.affiliation: Institut für Physiologie, Universität Regensburg, Universitätsstraße 31, 93053, Regensburg, Germany.
authors.forename: Rainer
authors.initials: R
authors.lastname: Schreiber
authors.affiliation: Institut für Physiologie, Universität Regensburg, Universitätsstraße 31, 93053, Regensburg, Germany. karl.kunzelmann@vkl.uni-regensburg.de.
authors.forename: Karl
authors.initials: K
authors.lastname: Kunzelmann
mesh_terms: D017209:Apoptosis; D048429:Cell Size; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D008564:Membrane Potentials; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C485976:LRRC8A protein, human; D008565:Membrane Proteins
keywords: AVD; LRRC8A; RVD, apoptotic volume decrease; VRAC; Volume regulation: regulatory volume decrease; Volume-activated anion channels