{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T20:01:51Z","timestamp":1791403311209,"version":"4.3.3"},"reference-count":59,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T00:00:00Z","timestamp":1759708800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T00:00:00Z","timestamp":1759708800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"DOI":"10.13039\/100000002","name":"U.S. Department of Health & Human Services | National Institutes of Health","doi-asserted-by":"publisher","award":["R01DK051610"],"award-info":[{"award-number":["R01DK051610"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Commun Biol"],"DOI":"10.1038\/s42003-025-08795-1","type":"journal-article","created":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T16:59:10Z","timestamp":1759769950000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["A conserved mechanism of LRRC8 channel inhibition by two structurally distinct drugs"],"prefix":"10.1038","volume":"8","author":[{"given":"Toshiki","family":"Yamada","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1789-762X","authenticated-orcid":false,"given":"Paola","family":"Bisignano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6552-3185","authenticated-orcid":false,"given":"Erkan","family":"Karakas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0032-8586","authenticated-orcid":false,"given":"Jerod S.","family":"Denton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,10,6]]},"reference":[{"key":"8795_CR1","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1085\/jgp.201812138","volume":"151","author":"K Strange","year":"2019","unstructured":"Strange, K., Yamada, T. & Denton, J. S. A 30-year journey from volume-regulated anion currents to molecular structure of the LRRC8 channel. J. Gen. Physiol. 151, 100\u2013117 (2019).","journal-title":"J. Gen. Physiol."},{"key":"8795_CR2","doi-asserted-by":"publisher","first-page":"1415","DOI":"10.1152\/physrev.2001.81.4.1415","volume":"81","author":"B Nilius","year":"2001","unstructured":"Nilius, B. & Droogmans, G. Ion channels and their functional role in vascular endothelium. Physiol. Rev. 81, 1415\u20131459 (2001).","journal-title":"Physiol. Rev."},{"key":"8795_CR3","doi-asserted-by":"publisher","first-page":"868","DOI":"10.1111\/apha.12450","volume":"213","author":"SF Pedersen","year":"2015","unstructured":"Pedersen, S. F., Klausen, T. K. & Nilius, B. The identification of a volume-regulated anion channel: an amazing Odyssey. Acta Physiol. (Oxf.) 213, 868\u2013881 (2015).","journal-title":"Acta Physiol. (Oxf.)"},{"key":"8795_CR4","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1186\/s12576-023-00897-x","volume":"74","author":"Y Okada","year":"2024","unstructured":"Okada, Y. Physiology of the volume-sensitive\/regulatory anion channel VSOR\/VRAC. Part 1: from its discovery and phenotype characterization to the molecular entity identification. J. Physiol. Sci. 74, 3 (2024).","journal-title":"J. Physiol. Sci."},{"key":"8795_CR5","doi-asserted-by":"publisher","first-page":"634","DOI":"10.1126\/science.1252826","volume":"344","author":"FK Voss","year":"2014","unstructured":"Voss, F. K. et al. Identification of LRRC8 heteromers as an essential component of the volume-regulated anion channel VRAC. Science 344, 634\u2013638 (2014).","journal-title":"Science"},{"key":"8795_CR6","doi-asserted-by":"publisher","first-page":"447","DOI":"10.1016\/j.cell.2014.03.024","volume":"157","author":"Z Qiu","year":"2014","unstructured":"Qiu, Z. et al. SWELL1, a plasma membrane protein, is an essential component of volume-regulated anion channel. Cell 157, 447\u2013458 (2014).","journal-title":"Cell"},{"key":"8795_CR7","doi-asserted-by":"publisher","first-page":"3013","DOI":"10.1113\/JP281577","volume":"599","author":"H Choi","year":"2021","unstructured":"Choi, H., Rohrbough, J. C., Nguyen, H. N., Dikalova, A. & Lamb, F. S. Oxidant-resistant LRRC8A\/C anion channels support superoxide production by NADPH oxidase 1. J. Physiol. 599, 3013\u20133036 (2021).","journal-title":"J. Physiol."},{"key":"8795_CR8","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1038\/s41590-021-01105-x","volume":"23","author":"AR Concepcion","year":"2022","unstructured":"Concepcion, A. R. et al. The volume-regulated anion channel LRRC8C suppresses T cell function by regulating cyclic dinucleotide transport and STING-p53 signaling. Nat. Immunol. 23, 287\u2013302 (2022).","journal-title":"Nat. Immunol."},{"key":"8795_CR9","doi-asserted-by":"publisher","first-page":"767","DOI":"10.1016\/j.immuni.2020.03.016","volume":"52","author":"C Zhou","year":"2020","unstructured":"Zhou, C. et al. Transfer of cGAMP into bystander cells via LRRC8 volume-regulated anion channels augments STING-mediated interferon responses and anti-viral immunity. Immunity 52, 767\u2013781 e766 (2020).","journal-title":"Immunity"},{"key":"8795_CR10","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2023.107016","volume":"198","author":"X Wu","year":"2023","unstructured":"Wu, X. et al. The volume regulated anion channel VRAC regulates NLRP3 inflammasome by modulating itaconate efflux and mitochondria function. Pharm. Res. 198, 107016 (2023).","journal-title":"Pharm. Res."},{"key":"8795_CR11","doi-asserted-by":"publisher","first-page":"347","DOI":"10.4049\/jimmunol.2300812","volume":"213","author":"L Wang","year":"2024","unstructured":"Wang, L. et al. ATP-elicited cation fluxes promote volume-regulated anion channel LRRC8\/VRAC transport cGAMP for antitumor immunity. J. Immunol. 213, 347\u2013361 (2024).","journal-title":"J. Immunol."},{"key":"8795_CR12","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-02664-0","volume":"9","author":"C Kang","year":"2018","unstructured":"Kang, C. et al. SWELL1 is a glucose sensor regulating beta-cell excitability and systemic glycaemia. Nat. Commun. 9, 367 (2018).","journal-title":"Nat. Commun."},{"key":"8795_CR13","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-28435-0","volume":"13","author":"SK Gunasekar","year":"2022","unstructured":"Gunasekar, S. K. et al. Small molecule SWELL1 complex induction improves glycemic control and nonalcoholic fatty liver disease in murine Type 2 diabetes. Nat. Commun. 13, 784 (2022).","journal-title":"Nat. Commun."},{"key":"8795_CR14","doi-asserted-by":"publisher","first-page":"813","DOI":"10.1016\/j.neuron.2019.03.029","volume":"102","author":"J Yang","year":"2019","unstructured":"Yang, J. et al. Glutamate-releasing SWELL1 Channel in astrocytes modulates synaptic transmission and promotes brain damage in stroke. Neuron 102, 813\u2013827.e816 (2019).","journal-title":"Neuron"},{"key":"8795_CR15","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.ade9931","volume":"9","author":"J Chu","year":"2023","unstructured":"Chu, J. et al. ATP-releasing SWELL1 channel in spinal microglia contributes to neuropathic pain. Sci. Adv. 9, eade9931 (2023).","journal-title":"Sci. Adv."},{"key":"8795_CR16","doi-asserted-by":"publisher","DOI":"10.14814\/phy2.14303","volume":"7","author":"A Afzal","year":"2019","unstructured":"Afzal, A. et al. The LRRC8 volume-regulated anion channel inhibitor, DCPIB, inhibits mitochondrial respiration independently of the channel. Physiol. Rep. 7, e14303 (2019).","journal-title":"Physiol. Rep."},{"key":"8795_CR17","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1124\/mol.112.080457","volume":"83","author":"NH Bowens","year":"2013","unstructured":"Bowens, N. H., Dohare, P., Kuo, Y. H. & Mongin, A. A. DCPIB, the proposed selective blocker of volume-regulated anion channels, inhibits several glutamate transport pathways in glial cells. Mol. Pharm. 83, 22\u201332 (2013).","journal-title":"Mol. Pharm."},{"key":"8795_CR18","doi-asserted-by":"publisher","first-page":"817","DOI":"10.1007\/s00424-016-1794-9","volume":"468","author":"W Deng","year":"2016","unstructured":"Deng, W., Mahajan, R., Baumgarten, C. M. & Logothetis, D. E. The ICl,swell inhibitor DCPIB blocks Kir channels that possess weak affinity for PIP2. Pflug. Arch. 468, 817\u2013824 (2016).","journal-title":"Pflug. Arch."},{"key":"8795_CR19","doi-asserted-by":"publisher","first-page":"2786","DOI":"10.1021\/acschemneuro.9b00010","volume":"10","author":"J Lv","year":"2019","unstructured":"Lv, J. et al. DCPIB, an inhibitor of volume-regulated anion channels, distinctly modulates K2P channels. ACS Chem. Neurosci. 10, 2786\u20132793 (2019).","journal-title":"ACS Chem. Neurosci."},{"key":"8795_CR20","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1016\/j.ejphar.2015.08.011","volume":"765","author":"T Fujii","year":"2015","unstructured":"Fujii, T. et al. Inhibition of gastric H+,K+-ATPase by 4-(2-butyl-6,7-dichloro-2-cyclopentylindan-1-on-5-yl)oxybutyric acid (DCPIB), an inhibitor of volume-regulated anion channel. Eur. J. Pharm. 765, 34\u201341 (2015).","journal-title":"Eur. J. Pharm."},{"key":"8795_CR21","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1080\/19336950.2022.2033511","volume":"16","author":"EE Figueroa","year":"2022","unstructured":"Figueroa, E. E. & Denton, J. S. A SWELL time to develop the molecular pharmacology of the volume-regulated anion channel (VRAC). Channels (Austin) 16, 27\u201336 (2022).","journal-title":"Channels (Austin)"},{"key":"8795_CR22","first-page":"e2401085","volume":"11","author":"J Chen","year":"2024","unstructured":"Chen, J. et al. The SWELL1 channel promotes ischemic brain damage by mediating neuronal swelling and glutamate toxicity. Adv. Sci. (Weinh.) 11, e2401085 (2024).","journal-title":"Adv. Sci. (Weinh.)"},{"key":"8795_CR23","doi-asserted-by":"crossref","unstructured":"Jeon, D., Ryu, K., Jo, S., Kim, I. & Namkung, W. VI-116, a novel potent inhibitor of VRAC with minimal effect on ANO1. Int. J. Mol. Sci. 23 (2022).","DOI":"10.3390\/ijms23095168"},{"key":"8795_CR24","doi-asserted-by":"publisher","first-page":"C857","DOI":"10.1152\/ajpcell.00281.2019","volume":"317","author":"EE Figueroa","year":"2019","unstructured":"Figueroa, E. E., Kramer, M., Strange, K. & Denton, J. S. CysLT1 receptor antagonists pranlukast and zafirlukast inhibit LRRC8-mediated volume regulated anion channels independently of the receptor. Am. J. Physiol. Cell Physiol. 317, C857\u2013C866 (2019).","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"8795_CR25","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1007\/164_2016_72","volume":"237","author":"T Tamada","year":"2017","unstructured":"Tamada, T. & Ichinose, M. Leukotriene receptor antagonists and antiallergy drugs. Handb. Exp. Pharm. 237, 153\u2013169 (2017).","journal-title":"Handb. Exp. Pharm."},{"key":"8795_CR26","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aax2518","volume":"5","author":"A Luginina","year":"2019","unstructured":"Luginina, A. et al. Structure-based mechanism of cysteinyl leukotriene receptor inhibition by antiasthmatic drugs. Sci. Adv. 5, eaax2518 (2019).","journal-title":"Sci. Adv."},{"key":"8795_CR27","doi-asserted-by":"crossref","unstructured":"Yanushkevich, S. et al. Recent advances in the structure, function and regulation of the volume-regulated anion channels and their role in immunity. J. Physiol. 603, 4255\u20134291 (2024).","DOI":"10.1113\/JP285200"},{"key":"8795_CR28","doi-asserted-by":"crossref","unstructured":"Takahashi, H., Yamada, T., Denton, J. S., Strange, K. & Karakas, E. Cryo-EM structures of an LRRC8 chimera with native functional properties reveal heptameric assembly. Elife 12 (2023).","DOI":"10.7554\/eLife.82431"},{"key":"8795_CR29","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1038\/s41594-022-00899-0","volume":"30","author":"S Rutz","year":"2023","unstructured":"Rutz, S., Deneka, D., Dittmann, A., Sawicka, M. & Dutzler, R. Structure of a volume-regulated heteromeric LRRC8A\/C channel. Nat. Struct. Mol. Biol. 30, 52\u201361 (2023).","journal-title":"Nat. Struct. Mol. Biol."},{"key":"8795_CR30","doi-asserted-by":"publisher","first-page":"240","DOI":"10.1038\/s42003-020-0951-z","volume":"3","author":"R Nakamura","year":"2020","unstructured":"Nakamura, R. et al. Cryo-EM structure of the volume-regulated anion channel LRRC8D isoform identifies features important for substrate permeation. Commun. Biol. 3, 240 (2020).","journal-title":"Commun. Biol."},{"key":"8795_CR31","doi-asserted-by":"crossref","unstructured":"Kefauver, J. M. et al. Structure of the human volume regulated anion channel. Elife 7 (2018).","DOI":"10.7554\/eLife.38461"},{"key":"8795_CR32","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2023.112926","volume":"42","author":"H Liu","year":"2023","unstructured":"Liu, H. et al. Structural insights into anion selectivity and activation mechanism of LRRC8 volume-regulated anion channels. Cell Rep. 42, 112926 (2023).","journal-title":"Cell Rep."},{"key":"8795_CR33","doi-asserted-by":"publisher","first-page":"841","DOI":"10.1038\/s41594-023-00944-6","volume":"30","author":"DM Kern","year":"2023","unstructured":"Kern, D. M. et al. Structural basis for assembly and lipid-mediated gating of LRRC8A:C volume-regulated anion channels. Nat. Struct. Mol. Biol. 30, 841\u2013852 (2023).","journal-title":"Nat. Struct. Mol. Biol."},{"key":"8795_CR34","doi-asserted-by":"crossref","unstructured":"Karakas, E., Strange, K. & Denton, J. S. Recent advances in structural characterization of volume-regulated anion channels (VRACs). J. Physiol. 603, 4201\u20134211(2025).","DOI":"10.1113\/JP286189"},{"key":"8795_CR35","doi-asserted-by":"crossref","unstructured":"Kern, D. M., Oh, S., Hite, R. K. & Brohawn, S. G. Cryo-EM structures of the DCPIB-inhibited volume-regulated anion channel LRRC8A in lipid nanodiscs. Elife 8 (2019).","DOI":"10.7554\/eLife.42636"},{"key":"8795_CR36","doi-asserted-by":"publisher","first-page":"1003","DOI":"10.1085\/jgp.201812016","volume":"150","author":"T Yamada","year":"2018","unstructured":"Yamada, T. & Strange, K. Intracellular and extracellular loops of LRRC8 are essential for volume-regulated anion channel function. J. Gen. Physiol. 150, 1003\u20131015 (2018).","journal-title":"J. Gen. Physiol."},{"key":"8795_CR37","doi-asserted-by":"publisher","first-page":"C293","DOI":"10.1152\/ajpcell.00454.2020","volume":"320","author":"T Yamada","year":"2021","unstructured":"Yamada, T., Figueroa, E. E., Denton, J. S. & Strange, K. LRRC8A homohexameric channels poorly recapitulate VRAC regulation and pharmacology. Am. J. Physiol. Cell Physiol. 320, C293\u2013C303 (2021).","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"8795_CR38","doi-asserted-by":"publisher","first-page":"1015","DOI":"10.1085\/jgp.94.6.1015","volume":"94","author":"JD McCann","year":"1989","unstructured":"McCann, J. D., Li, M. & Welsh, M. J. Identification and regulation of whole-cell chloride currents in airway epithelium. J. Gen. Physiol. 94, 1015\u20131036 (1989).","journal-title":"J. Gen. Physiol."},{"key":"8795_CR39","doi-asserted-by":"publisher","first-page":"C1111","DOI":"10.1152\/ajpcell.1989.256.6.C1111","volume":"256","author":"RT Worrell","year":"1989","unstructured":"Worrell, R. T., Butt, A. G., Cliff, W. H. & Frizzell, R. A. A volume-sensitive chloride conductance in human colonic cell line T84. Am. J. Physiol. 256, C1111\u2013C1119 (1989).","journal-title":"Am. J. Physiol."},{"key":"8795_CR40","doi-asserted-by":"publisher","first-page":"661","DOI":"10.1085\/jgp.105.5.661","volume":"105","author":"PS Jackson","year":"1995","unstructured":"Jackson, P. S. & Strange, K. Characterization of the voltage-dependent properties of a volume-sensitive anion conductance. J. Gen. Physiol. 105, 661\u2013676 (1995).","journal-title":"J. Gen. Physiol."},{"key":"8795_CR41","doi-asserted-by":"publisher","first-page":"5526","DOI":"10.1021\/acs.jctc.0c00395","volume":"16","author":"Y Miao","year":"2020","unstructured":"Miao, Y., Bhattarai, A. & Wang, J. Ligand Gaussian accelerated molecular dynamics (LiGaMD): characterization of ligand binding thermodynamics and kinetics. J. Chem. Theory Comput. 16, 5526\u20135547 (2020).","journal-title":"J. Chem. Theory Comput"},{"key":"8795_CR42","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1038\/s44318-024-00322-y","volume":"44","author":"M Quinodoz","year":"2025","unstructured":"Quinodoz, M. et al. De novo variants in LRRC8C resulting in constitutive channel activation cause a human multisystem disorder. EMBO J. 44, 413\u2013436 (2025).","journal-title":"EMBO J."},{"key":"8795_CR43","doi-asserted-by":"publisher","first-page":"797","DOI":"10.1038\/s41594-018-0109-6","volume":"25","author":"G Kasuya","year":"2018","unstructured":"Kasuya, G. et al. Cryo-EM structures of the human volume-regulated anion channel LRRC8. Nat. Struct. Mol. Biol. 25, 797\u2013804 (2018).","journal-title":"Nat. Struct. Mol. Biol."},{"key":"8795_CR44","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1038\/s41586-024-07487-w","volume":"630","author":"J Abramson","year":"2024","unstructured":"Abramson, J. et al. Accurate structure prediction of biomolecular interactions with AlphaFold 3. Nature 630, 493\u2013500 (2024).","journal-title":"Nature"},{"key":"8795_CR45","doi-asserted-by":"publisher","first-page":"633","DOI":"10.1007\/s00424-010-0842-0","volume":"460","author":"CY Hernandez-Carballo","year":"2010","unstructured":"Hernandez-Carballo, C. Y., De Santiago-Castillo, J. A., Rosales-Saavedra, T., Perez-Cornejo, P. & Arreola, J. Control of volume-sensitive chloride channel inactivation by the coupled action of intracellular chloride and extracellular protons. Pflug. Arch. 460, 633\u2013644 (2010).","journal-title":"Pflug. Arch."},{"key":"8795_CR46","doi-asserted-by":"publisher","first-page":"1182","DOI":"10.1016\/S0026-895X(24)23228-4","volume":"57","author":"S Ravasi","year":"2000","unstructured":"Ravasi, S., Capra, V., Mezzetti, M., Nicosia, S. & Rovati, G. E. A kinetic binding study to evaluate the pharmacological profile of a specific leukotriene C(4) binding site not coupled to contraction in human lung parenchyma. Mol. Pharm. 57, 1182\u20131189 (2000).","journal-title":"Mol. Pharm."},{"key":"8795_CR47","doi-asserted-by":"publisher","first-page":"17040","DOI":"10.1074\/jbc.M116.739342","volume":"291","author":"F Ullrich","year":"2016","unstructured":"Ullrich, F., Reincke, S. M., Voss, F. K., Stauber, T. & Jentsch, T. J. Inactivation and anion selectivity of volume-regulated anion channels (VRACs) depend on c-terminal residues of the first extracellular loop. J. Biol. Chem. 291, 17040\u201317048 (2016).","journal-title":"J. Biol. Chem."},{"key":"8795_CR48","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1085\/jgp.110.3.313","volume":"110","author":"T Voets","year":"1997","unstructured":"Voets, T., Droogmans, G. & Nilius, B. Modulation of voltage-dependent properties of a swelling-activated Cl - current. J. Gen. Physiol. 110, 313\u2013325 (1997).","journal-title":"J. Gen. Physiol."},{"key":"8795_CR49","doi-asserted-by":"publisher","first-page":"613","DOI":"10.1113\/jphysiol.1996.sp021408","volume":"493","author":"M Gosling","year":"1996","unstructured":"Gosling, M., Poyner, D. R. & Smith, J. W. Effects of arachidonic acid upon the volume-sensitive chloride current in rat osteoblast-like (ROS 17\/2.8) cells. J. Physiol. 493, 613\u2013623 (1996).","journal-title":"J. Physiol."},{"key":"8795_CR50","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1016\/S0162-0134(98)10042-9","volume":"71","author":"L Rulisek","year":"1998","unstructured":"Rulisek, L. & Vondrasek, J. Coordination geometries of selected transition metal ions (Co2+, Ni2+, Cu2+, Zn2+, Cd2+, and Hg2+) in metalloproteins. J. Inorg. Biochem. 71, 115\u2013127 (1998).","journal-title":"J. Inorg. Biochem."},{"key":"8795_CR51","doi-asserted-by":"publisher","first-page":"13440","DOI":"10.1074\/jbc.RA118.002853","volume":"293","author":"P Zhou","year":"2018","unstructured":"Zhou, P., Polovitskaya, M. M. & Jentsch, T. J. LRRC8 N termini influence pore properties and gating of volume-regulated anion channels (VRACs). J. Biol. Chem. 293, 13440\u201313451 (2018).","journal-title":"J. Biol. Chem."},{"key":"8795_CR52","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-25742-w","volume":"12","author":"D Deneka","year":"2021","unstructured":"Deneka, D. et al. Allosteric modulation of LRRC8 channels by targeting their cytoplasmic domains. Nat. Commun. 12, 5435 (2021).","journal-title":"Nat. Commun."},{"key":"8795_CR53","doi-asserted-by":"crossref","unstructured":"Konig, B., Hao, Y., Schwartz, S., Plested, A. J. & Stauber, T. A FRET sensor of C-terminal movement reveals VRAC activation by plasma membrane DAG signaling rather than ionic strength. Elife 8 (2019).","DOI":"10.7554\/eLife.45421"},{"key":"8795_CR54","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1085\/jgp.108.3.177","volume":"108","author":"K Meyer","year":"1996","unstructured":"Meyer, K. & Korbmacher, C. Cell swelling activates ATP-dependent voltage-gated Cl - channels in M-1 mouse cortical collecting duct cells. J. Gen. Physiol. 108, 177\u2013193 (1996).","journal-title":"J. Gen. Physiol."},{"key":"8795_CR55","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1016\/j.cell.2015.12.031","volume":"164","author":"R Syeda","year":"2016","unstructured":"Syeda, R. et al. LRRC8 Proteins Form Volume-Regulated Anion Channels that Sense Ionic Strength. Cell 164, 499\u2013511 (2016).","journal-title":"Cell"},{"key":"8795_CR56","unstructured":"Molecular Operating Environment (MOE), 2024.0601. Chemical Computing Group ULC, 1010 Sherbrooke St. West, Suite 910, Montreal, QC, Canada, H3A 2R7 (2023)."},{"key":"8795_CR57","doi-asserted-by":"crossref","unstructured":"Case, D. A. et al. AmberTools. J Chem. Inf. Model. 63, 6183\u20136191 (2023).","DOI":"10.1021\/acs.jcim.3c01153"},{"key":"8795_CR58","unstructured":"Frisch, M. J. T. et al. Gaussian 16, Revision C.01, Gaussian, (Inc., Wallingford CT, 2016)."},{"key":"8795_CR59","doi-asserted-by":"publisher","first-page":"354","DOI":"10.1016\/S0263-7855(97)00009-X","volume":"14","author":"OS Smart","year":"1996","unstructured":"Smart, O. S., Neduvelil, J. G., Wang, X., Wallace, B. A. & Sansom, M. S. HOLE: a program for the analysis of the pore dimensions of ion channel structural models. J. Mol. Graph 14, 354\u2013360 (1996).","journal-title":"J. Mol. Graph"}],"container-title":["Communications Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s42003-025-08795-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s42003-025-08795-1","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s42003-025-08795-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T18:03:05Z","timestamp":1759773785000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s42003-025-08795-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,6]]},"references-count":59,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["8795"],"URL":"https:\/\/doi.org\/10.1038\/s42003-025-08795-1","relation":{},"ISSN":["2399-3642"],"issn-type":[{"value":"2399-3642","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,6]]},"assertion":[{"value":"25 June 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 August 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 October 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"1432"}}