biostudies-literatureKostritskaia YBundesministerium für Bildung und Forschung (BMBF)4329-4344https://www.ebi.ac.uk/biostudies/studies/S-EPMC12333907biostudies-literatureUnknown603(15)Volume-regulated anion channels (VRACs) formed by leucin-rich repeat containing 8 (LRRC8) proteins play a pivotal role in regulatory volume decrease by mediating the release of chloride and organic osmolytes. Apart from the regulation of cell volume, LRRC8/VRAC function underlies numerous physiological processes in vertebrate cells including membrane potential regulation, glutamate release and apoptosis. LRRC8/VRACs are also permeable to antibiotics and anti-cancer drugs, representing therefore important therapeutic targets. The activation mechanisms for LRRC8/VRACs are still unclear. Besides through osmotic cell swelling, LRRC8/VRACs can be activated by various stimuli under isovolumetric conditions. Sphingosine-1-phosphate (S1P), an important signalling lipid, which signals through a famThe Journal of physiologySphingosine-1-phosphate activates LRRC8 volume-regulated anion channels through Gβγ signalling.PMC12333907031A314Klemmer AKostritskaia YPervaiz SKlussendorf MStauber TfalseSphingosine-1-phosphate activates LRRC8 volume-regulated anion channels through Gβγ signalling.Volume-regulated anion channels (VRACs) formed by leucin-rich repeat containing 8 (LRRC8) proteins play a pivotal role in regulatory volume decrease by mediating the release of chloride and organic osmolytes. Apart from the regulation of cell volume, LRRC8/VRAC function underlies numerous physiological processes in vertebrate cells including membrane potential regulation, glutamate release and apoptosis. LRRC8/VRACs are also permeable to antibiotics and anti-cancer drugs, representing therefore important therapeutic targets. The activation mechanisms for LRRC8/VRACs are still unclear. Besides through osmotic cell swelling, LRRC8/VRACs can be activated by various stimuli under isovolumetric conditions. Sphingosine-1-phosphate (S1P), an important signalling lipid, which signals through a fam2025-01-01T00:00:00Z2025 Aug2026-05-01T08:40:22Z2026-04-19T03:08:09.523ZS-EPMC123339073949649310.1113/JP286665