Skip to content
Licensed Unlicensed Requires Authentication Published by De Gruyter August 24, 2019

More than just a pressure relief valve: physiological roles of volume-regulated LRRC8 anion channels

  • Lingye Chen , Benjamin König , Tianbao Liu , Sumaira Pervaiz , Yasmin S. Razzaque and Tobias Stauber ORCID logo EMAIL logo
From the journal Biological Chemistry

Abstract

The volume-regulated anion channel (VRAC) is a key player in the volume regulation of vertebrate cells. This ubiquitously expressed channel opens upon osmotic cell swelling and potentially other cues and releases chloride and organic osmolytes, which contributes to regulatory volume decrease (RVD). A plethora of studies have proposed a wide range of physiological roles for VRAC beyond volume regulation including cell proliferation, differentiation and migration, apoptosis, intercellular communication by direct release of signaling molecules and by supporting the exocytosis of insulin. VRAC was additionally implicated in pathological states such as cancer therapy resistance and excitotoxicity under ischemic conditions. Following extensive investigations, 5 years ago leucine-rich repeat-containing family 8 (LRRC8) heteromers containing LRRC8A were identified as the pore-forming components of VRAC. Since then, molecular biological approaches have allowed further insight into the biophysical properties and structure of VRAC. Heterologous expression, siRNA-mediated downregulation and genome editing in cells, as well as the use of animal models have enabled the assessment of the proposed physiological roles, together with the identification of new functions including spermatogenesis and the uptake of antibiotics and platinum-based cancer drugs. This review discusses the recent molecular biological insights into the physiology of VRAC in relation to its previously proposed roles.

Acknowledgments

The research group is supported by the German Federal Ministry of Education and Research (BMBF, e:Bio grant no. 031A314 to T.S.) and PhD fellowships from the Oversea Study Program of Guangzhou Elite Project (L.C.), the China Scholarship Council (T.L.) and the University of Punjab (S.P.).

References

Abascal, F. and Zardoya, R. (2012). LRRC8 proteins share a common ancestor with pannexins, and may form hexameric channels involved in cell-cell communication. Bioessays 34, 551–560.10.1002/bies.201100173Search in Google Scholar PubMed

Akita, T. and Okada, Y. (2014). Characteristics and roles of the volume-sensitive outwardly rectifying (VSOR) anion channel in the central nervous system. Neuroscience 275C, 211–231.10.1016/j.neuroscience.2014.06.015Search in Google Scholar PubMed

Akita, T., Fedorovich, S.V., and Okada, Y. (2011). Ca2+ nanodomain-mediated component of swelling-induced volume-sensitive outwardly rectifying anion current triggered by autocrine action of ATP in mouse astrocytes. Cell. Physiol. Biochem. 28, 1181–1190.10.1159/000335867Search in Google Scholar PubMed

Ashcroft, F.M. and Rorsman, P. (2013). K(ATP) channels and islet hormone secretion: new insights and controversies. Nat. Rev. Endocrinol. 9, 660–669.10.1038/nrendo.2013.166Search in Google Scholar PubMed PubMed Central

Bach, M.D., Sørensen, B.H., and Lambert, I.H. (2018). Stress-induced modulation of volume-regulated anions channels in human alveolar carcinoma cells. Physiol. Rep. 6, e13869.10.14814/phy2.13869Search in Google Scholar PubMed PubMed Central

Bao, J., Perez, C.J., Kim, J., Zhang, H., Murphy, C.J., Hamidi, T., Jaubert, J., Platt, C.D., Chou, J., Deng, M., et al. (2018). Deficient LRRC8A-dependent volume-regulated anion channel activity is associated with male infertility in mice. JCI Insight 3, e99767.10.1172/jci.insight.99767Search in Google Scholar PubMed PubMed Central

Behe, P., Foote, J.R., Levine, A.P., Platt, C.D., Chou, J., Benavides, F., Geha, R.S., and Segal, A.W. (2017). The LRRC8A mediated “swell activated” chloride conductance is dispensable for vacuolar homeostasis in neutrophils. Front. Pharmacol. 8, 262.10.3389/fphar.2017.00262Search in Google Scholar PubMed PubMed Central

Benfenati, V., Caprini, M., Nicchia, G.P., Rossi, A., Dovizio, M., Cervetto, C., Nobile, M., and Ferroni, S. (2009). Carbenoxolone inhibits volume-regulated anion conductance in cultured rat cortical astroglia. Channels 3, 323–336.10.4161/chan.3.5.9568Search in Google Scholar PubMed

Best, L. and Brown, P.D. (2009). Studies of the mechanism of activation of the volume-regulated anion channel in rat pancreatic β-cells. J. Membr. Biol. 230, 83–91.10.1007/s00232-009-9189-xSearch in Google Scholar PubMed

Best, L., Yates, A.P., Decher, N., Steinmeyer, K., and Nilius, B. (2004). Inhibition of glucose-induced electrical activity in rat pancreatic beta-cells by DCPIB, a selective inhibitor of volume-sensitive anion currents. Eur. J. Pharmacol. 489, 13–19.10.1016/j.ejphar.2004.02.030Search in Google Scholar PubMed

Best, L., Brown, P.D., Sener, A., and Malaisse, W.J. (2010). Electrical activity in pancreatic islet cells: the VRAC hypothesis. Islets 2, 59–64.10.4161/isl.2.2.11171Search in Google Scholar

Bortner, C.D. and Cidlowski, J.A. (1998). A necessary role for cell shrinkage in apoptosis. Biochem. Pharmacol. 56, 1549–1559.10.1016/S0006-2952(98)00225-1Search in Google Scholar

Browe, D.M. and Baumgarten, C.M. (2006). EGFR kinase regulates volume-sensitive chloride current elicited by integrin stretch via PI-3K and NADPH oxidase in ventricular myocytes. J. Gen. Physiol. 127, 237–251.10.1085/jgp.200509366Search in Google Scholar PubMed PubMed Central

Bugiani, M., Dubey, M., Breur, M., Postma, N.L., Dekker, M.P., Ter Braak, T., Boschert, U., Abbink, T.E.M., Mansvelder, H.D., Min, R., et al. (2017). Megalencephalic leukoencephalopathy with cysts: the Glialcam-null mouse model. Ann. Clin. Transl. Neurol. 4, 450–465.10.1002/acn3.405Search in Google Scholar PubMed PubMed Central

Burow, P., Klapperstück, M., and Markwardt, F. (2015). Activation of ATP secretion via volume-regulated anion channels by sphingosine-1-phosphate in RAW macrophages. Pflüger’s Arch. 467, 1215–1226.10.1007/s00424-014-1561-8Search in Google Scholar PubMed

Cahalan, M.D. and Lewis, R.S. (1988). Role of potassium and chloride channels in volume regulation by T lymphocytes. Soc. Gen. Physiol. Ser. 43, 281–301.Search in Google Scholar

Cai, S., Zhang, T., Zhang, D., Qiu, G., and Liu, Y. (2015). Volume-sensitive chloride channels are involved in cisplatin treatment of osteosarcoma. Mol. Med. Rep. 11, 2465–2470.10.3892/mmr.2014.3068Search in Google Scholar PubMed PubMed Central

Cannon, C.L., Basavappa, S., and Strange, K. (1998). Intracellular ionic strength regulates the volume sensitivity of a swelling-activated anion channel. Am. J. Physiol. 275, C416–C422.10.1152/ajpcell.1998.275.2.C416Search in Google Scholar PubMed

Catacuzzeno, L., Michelucci, A., Sforna, L., Aiello, F., Sciaccaluga, M., Fioretti, B., Castigli, E., and Franciolini, F. (2014). Identification of key signaling molecules involved in the activation of the swelling-activated chloride current in human glioblastoma cells. J. Membr. Biol. 247, 45–55.10.1007/s00232-013-9609-9Search in Google Scholar PubMed

Catalán, M.A., Kondo, Y., Peña-Münzenmayer, G., Jaramillo, Y., Liu, F., Choi, S., Crandall, E., Borok, Z., Flodby, P., Shull, G.E., et al. (2015). A fluid secretion pathway unmasked by acinar-specific Tmem16A gene ablation in the adult mouse salivary gland. Proc. Natl. Acad. Sci. U.S.A. 112, 2263–2268.10.1073/pnas.1415739112Search in Google Scholar PubMed PubMed Central

Chang, C.C., Chang, Y.S., Huang, H.Y., Yeh, K.T., Liu, T.C., and Chang, J.G. (2018). Determination of the mutational landscape in Taiwanese patients with papillary thyroid cancer by whole-exome sequencing. Hum. Pathol. 78, 151–158.10.1016/j.humpath.2018.04.023Search in Google Scholar PubMed

Choi, H., Ettinger, N., Rohrbough, J., Dikalova, A., Nguyen, H.N., and Lamb, F.S. (2016). LRRC8A channels support TNFalpha-induced superoxide production by Nox1 which is required for receptor endocytosis. Free Radic. Biol. Med. 101, 413–423.10.1016/j.freeradbiomed.2016.11.003Search in Google Scholar PubMed PubMed Central

Compan, V., Baroja-Mazo, A., López-Castejón, G., Gomez, A.I., Martínez, C.M., Angosto, D., Montero, M.T., Herranz, A.S., Bazán, E., Reimers, D., et al. (2012). Cell volume regulation modulates NLRP3 inflammasome activation. Immunity 37, 487–500.10.1016/j.immuni.2012.06.013Search in Google Scholar PubMed

Deneka, D., Sawicka, M., Lam, A.K.M., Paulino, C., and Dutzler, R. (2018). Structure of a volume-regulated anion channel of the LRRC8 family. Nature 558, 254–259.10.1038/s41586-018-0134-ySearch in Google Scholar PubMed

Elorza-Vidal, X., Sirisi, S., Gaitán-Peñas, H., Pérez-Rius, C., Alonso-Gardón, M., Armand-Ugón, M., Lanciotti, A., Brignone, M.S., Prat, E., Nunes, V., et al. (2018). GlialCAM/MLC1 modulates LRRC8/VRAC currents in an indirect manner: implications for megalencephalic leukoencephalopathy. Neurobiol. Dis. 119, 88–99.10.1016/j.nbd.2018.07.031Search in Google Scholar PubMed

Elorza-Vidal, X., Gaitán-Peñas, H., and Estévez, R. (2019). Chloride channels in astrocytes: structure, roles in brain homeostasis and implications in disease. Int. J. Mol. Sci. 20, 1034.10.3390/ijms20051034Search in Google Scholar PubMed PubMed Central

Emma, F., McManus, M., and Strange, K. (1997). Intracellular electrolytes regulate the volume set point of the organic osmolyte/anion channel VSOAC. Am. J. Physiol. 272, C1766–C1775.10.1152/ajpcell.1997.272.6.C1766Search in Google Scholar PubMed

Estevez, A.Y., Bond, T., and Strange, K. (2001). Regulation of ICl,swell in neuroblastoma cells by G protein signaling pathways. Am. J. Physiol. 281, C89–C98.10.1152/ajpcell.2001.281.1.C89Search in Google Scholar PubMed

Feustel, P.J., Jin, Y., and Kimelberg, H.K. (2004). Volume-regulated anion channels are the predominant contributors to release of excitatory amino acids in the ischemic cortical penumbra. Stroke 35, 1164–1168.10.1161/01.STR.0000124127.57946.a1Search in Google Scholar PubMed

Formaggio, F., Saracino, E., Mola, M.G., Rao, S.B., Amiry-Moghaddam, M., Muccini, M., Zamboni, R., Nicchia, G.P., Caprini, M., and Benfenati, V. (2019). LRRC8A is essential for swelling-activated chloride current and for regulatory volume decrease in astrocytes. FASEB J. 33, 101–113.10.1096/fj.201701397RRSearch in Google Scholar PubMed

Friard, J., Tauc, M., Cougnon, M., Compan, V., Duranton, C., and Rubera, I. (2017). Comparative effects of chloride channel inhibitors on LRRC8/VRAC-mediated chloride conductance. Front. Pharmacol. 8, 328.10.3389/fphar.2017.00328Search in Google Scholar PubMed PubMed Central

Fujii, Y., Maekawa, S., and Morita, M. (2017). Astrocyte calcium waves propagate proximally by gap junction and distally by extracellular diffusion of ATP released from volume-regulated anion channels. Sci. Rep. 7, 13115.10.1038/s41598-017-13243-0Search in Google Scholar PubMed PubMed Central

Fujii, T., Shimizu, T., Yamamoto, S., Funayama, K., Fujita, K., Tabuchi, Y., Ikari, A., Takeshima, H., and Sakai, H. (2018). Crosstalk between Na+,K+-ATPase and a volume-regulated anion channel in membrane microdomains of human cancer cells. Biochim. Biophys. Acta Mol. Basis Dis. 1864, 3792–3804.10.1016/j.bbadis.2018.09.014Search in Google Scholar PubMed

Gaitán-Peñas, H., Gradogna, A., Laparra-Cuervo, L., Solsona, C., Fernández-Dueñas, V., Barrallo-Gimeno, A., Ciruela, F., Lakadamyali, M., Pusch, M., and Estévez, R. (2016). Investigation of LRRC8-mediated volume-regulated anion currents in Xenopus oocytes. Biophys. J. 111, 1429–1443.10.1016/j.bpj.2016.08.030Search in Google Scholar PubMed PubMed Central

Gasull, X., Castany, M., Castellanos, A., Rezola, M., Andrés-Bilbé, A., Canut, M.I., Estévez, R., Borrás, T., and Comes, N. (2019). The LRRC8-mediated volume-regulated anion channel is altered in glaucoma. Sci. Rep. 9, 5392.10.1038/s41598-019-41524-3Search in Google Scholar PubMed PubMed Central

Ghosh, A., Khandelwal, N., Kumar, A., and Bera, A.K. (2017). Leucine-rich repeat-containing 8B protein is associated with the endoplasmic reticulum Ca2+ leak in HEK293 cells. J. Cell Sci. 130, 3818–3828.Search in Google Scholar

Gradogna, A., Gaitán-Peñas, H., Boccaccio, A., Estévez, R., and Pusch, M. (2017a). Cisplatin activates volume sensitive LRRC8 channel mediated currents in Xenopus oocytes. Channels 11, 254–260.10.1080/19336950.2017.1284717Search in Google Scholar PubMed PubMed Central

Gradogna, A., Gavazzo, P., Boccaccio, A., and Pusch, M. (2017b). Subunit-dependent oxidative stress sensitivity of LRRC8 volume-regulated anion channels. J. Physiol. 595, 6719–6733.10.1113/JP274795Search in Google Scholar PubMed PubMed Central

Harrigan, T.J., Abdullaev, I.F., Jourd’heuil, D., and Mongin, A.A. (2008). Activation of microglia with zymosan promotes excitatory amino acid release via volume-regulated anion channels: the role of NADPH oxidases. J. Neurochem. 106, 2449–2462.10.1111/j.1471-4159.2008.05553.xSearch in Google Scholar PubMed PubMed Central

Hasegawa, Y., Shimizu, T., Takahashi, N., and Okada, Y. (2012). The apoptotic volume decrease is an upstream event of MAP kinase activation during staurosporine-induced apoptosis in HeLa cells. Int. J. Mol. Sci. 13, 9363–9379.10.3390/ijms13079363Search in Google Scholar PubMed PubMed Central

Hayashi, T., Nozaki, Y., Nishizuka, M., Ikawa, M., Osada, S., and Imagawa, M. (2011). Factor for adipocyte differentiation 158 gene disruption prevents the body weight gain and insulin resistance induced by a high-fat diet. Biol. Pharm. Bull. 34, 1257–1263.10.1248/bpb.34.1257Search in Google Scholar PubMed

Hazama, A., and Okada, Y. (1988). Ca2+ sensitivity of volume-regulatory K+ and Cl channels in cultured human epithelial cells. J. Physiol. 402, 687–702.10.1113/jphysiol.1988.sp017229Search in Google Scholar PubMed PubMed Central

Hermoso, M., Olivero, P., Torres, R., Riveros, A., Quest, A.F., and Stutzin, A. (2004). Cell volume regulation in response to hypotonicity is impaired in HeLa cells expressing a protein kinase Cα mutant lacking kinase activity. J. Biol. Chem. 279, 17681–17689.10.1074/jbc.M304506200Search in Google Scholar PubMed

Hisadome, K., Koyama, T., Kimura, C., Droogmans, G., Ito, Y., and Oike, M. (2002). Volume-regulated anion channels serve as an auto/paracrine nucleotide release pathway in aortic endothelial cells. J. Gen. Physiol. 119, 511–520.10.1085/jgp.20028540Search in Google Scholar PubMed PubMed Central

Hoffmann, E.K., Schettino, T., and Marshall, W.S. (2007). The role of volume-sensitive ion transport systems in regulation of epithelial transport. Comp. Biochem. Physiol. 148, 29–43.10.1016/j.cbpa.2006.11.023Search in Google Scholar PubMed

Hoffmann, E.K., Lambert, I.H., and Pedersen, S.F. (2009). Physiology of cell volume regulation in vertebrates. Physiol. Rev. 89, 193–277.10.1152/physrev.00037.2007Search in Google Scholar PubMed

Hyzinski-García, M.C., Rudkouskaya, A., and Mongin, A.A. (2014). LRRC8A protein is indispensable for swelling-activated and ATP-induced release of excitatory amino acids in rat astrocytes. J. Physiol. 592, 4855–4862.10.1113/jphysiol.2014.278887Search in Google Scholar PubMed PubMed Central

Inoue, H., Ohtaki, H., Nakamachi, T., Shioda, S., and Okada, Y. (2007). Anion channel blockers attenuate delayed neuronal cell death induced by transient forebrain ischemia. J. Neurosci. Res. 85, 1427–1435.10.1002/jnr.21279Search in Google Scholar PubMed

Ise, T., Shimizu, T., Lee, E.L., Inoue, H., Kohno, K., and Okada, Y. (2005). Roles of volume-sensitive Cl channel in cisplatin-induced apoptosis in human epidermoid cancer cells. J. Membr. Biol. 205, 139–145.10.1007/s00232-005-0779-ySearch in Google Scholar PubMed

Jackson, P.S. and Strange, K. (1993). Volume-sensitive anion channels mediate swelling-activated inositol and taurine efflux. Am. J. Physiol. 265, C1489–C1500.10.1152/ajpcell.1993.265.6.C1489Search in Google Scholar PubMed

Jackson, P.S., Morrison, R., and Strange, K. (1994). The volume-sensitive organic osmolyte-anion channel VSOAC is regulated by nonhydrolytic ATP binding. Am. J. Physiol. 267, C1203–C1209.10.1152/ajpcell.1994.267.5.C1203Search in Google Scholar PubMed

Jackson, P.S., Churchwell, K., Ballatori, N., Boyer, J.L., and Strange, K. (1996). Swelling-activated anion conductance in skate hepatocytes: regulation by cell Cl and ATP. Am. J. Physiol. 270, C57–C66.10.1152/ajpcell.1996.270.1.C57Search in Google Scholar PubMed

Jentsch, T.J. (2016). VRACs and other ion channels and transporters in the regulation of cell volume and beyond. Nat. Rev. Mol. Cell. Biol. 17, 293–307.10.1038/nrm.2016.29Search in Google Scholar PubMed

Kalogeris, T., Baines, C.P., Krenz, M., and Korthuis, R.J. (2012). Cell biology of ischemia/reperfusion injury. Int. Rev. Cell. Mol. Biol. 298, 229–317.10.1016/B978-0-12-394309-5.00006-7Search in Google Scholar PubMed PubMed Central

Kang, C., Xie, L., Gunasekar, S.K., Mishra, A., Zhang, Y., Pai, S., Gao, Y., Kumar, A., Norris, A.W., Stephens, S.B., et al. (2018). SWELL1 is a glucose sensor regulating β-cell excitability and systemic glycaemia. Nat. Commun. 9, 367.10.1038/s41467-017-02664-0Search in Google Scholar PubMed PubMed Central

Kasuya, G., Nakane, T., Yokoyama, T., Jia, Y., Inoue, M., Watanabe, K., Nakamura, R., Nishizawa, T., Kusakizako, T., Tsutsumi, A., et al. (2018). Cryo-EM structures of the human volume-regulated anion channel LRRC8. Nat. Struct. Mol. Biol. 25, 797–804.10.1038/s41594-018-0109-6Search in Google Scholar PubMed

Kefauver, J.M., Saotome, K., Dubin, A.E., Pallesen, J., Cottrell, C.A., Cahalan, S.M., Qiu, Z., Hong, G., Crowley, C.S., Whitwam, T., et al. (2018). Structure of the human volume regulated anion channel. eLife 7, e38461.10.7554/eLife.38461Search in Google Scholar PubMed PubMed Central

Kenagy, R.D., Min, S.K., Mulvihill, E., and Clowes, A.W. (2011). A link between smooth muscle cell death and extracellular matrix degradation during vascular atrophy. J. Vasc. Surg. 54, 182–191.e124.10.1016/j.jvs.2010.12.070Search in Google Scholar PubMed PubMed Central

Kern, D.M., Oh, S., Hite, R.K., and Brohawn, S.G. (2019). Cryo-EM structures of the DCPIB-inhibited volume-regulated anion channel LRRC8A in lipid nanodiscs. eLife 8, e42636.10.7554/eLife.42636Search in Google Scholar PubMed PubMed Central

Kimelberg, H.K. (2005). Astrocytic swelling in cerebral ischemia as a possible cause of injury and target for therapy. Glia 50, 389–397.10.1002/glia.20174Search in Google Scholar PubMed

Kimelberg, H.K., Goderie, S.K., Higman, S., Pang, S., and Waniewski, R.A. (1990). Swelling-induced release of glutamate, aspartate, and taurine from astrocyte cultures. J. Neurosci. 10, 1583–1591.10.1523/JNEUROSCI.10-05-01583.1990Search in Google Scholar

Kimelberg, H.K., Feustel, P.J., Jin, Y., Paquette, J., Boulos, A., Keller Jr., R.W., and Tranmer, B.I. (2000). Acute treatment with tamoxifen reduces ischemic damage following middle cerebral artery occlusion. Neuroreport 11, 2675–2679.10.1097/00001756-200008210-00014Search in Google Scholar PubMed

Kirk, K., Ellory, J.C., and Young, J.D. (1992). Transport of organic substrates via a volume-activated channel. J. Biol. Chem. 267, 23475–23478.10.1016/S0021-9258(18)35862-9Search in Google Scholar

Kittl, M., Dobias, H., Beyreis, M., Kiesslich, T., Mayr, C., Gaisberger, M., Ritter, M., Kerschbaum, H.H., and Jakab, M. (2018). Glycine induces migration of microglial BV-2 cells via SNAT-mediated cell swelling. Cell. Physiol. Biochem. 50, 1460–1473.10.1159/000494646Search in Google Scholar PubMed

Klausen, T.K., Bergdahl, A., Hougaard, C., Christophersen, P., Pedersen, S.F., and Hoffmann, E.K. (2007). Cell cycle-dependent activity of the volume- and Ca2+-activated anion currents in Ehrlich lettre ascites cells. J. Cell. Physiol. 210, 831–842.10.1002/jcp.20918Search in Google Scholar PubMed

König, B. and Stauber, T. (2019). Biophysics and structure-function relationships of LRRC8-formed volume-regulated anion channels. Biophys. J. 116, 1185–1193.10.1016/j.bpj.2019.02.014Search in Google Scholar PubMed PubMed Central

Kumagai, K., Toyoda, F., Staunton, C.A., Maeda, T., Okumura, N., Matsuura, H., Matsusue, Y., Imai, S., and Barrett-Jolley, R. (2016). Activation of a chondrocyte volume-sensitive Cl conductance prior to macroscopic cartilage lesion formation in the rabbit knee anterior cruciate ligament transection osteoarthritis model. Osteoarthr. Cartil. 24, 1786–1794.10.1016/j.joca.2016.05.019Search in Google Scholar PubMed PubMed Central

Kumar, L., Chou, J., Yee, C.S., Borzutzky, A., Vollmann, E.H., von Andrian, U.H., Park, S.Y., Hollander, G., Manis, J.P., Poliani, P.L., et al. (2014). Leucine-rich repeat containing 8A (LRRC8A) is essential for T lymphocyte development and function. J. Exp. Med. 211, 929–942.10.1084/jem.20131379Search in Google Scholar PubMed PubMed Central

Kunzelmann, K. (2016). Ion channels in regulated cell death. Cell. Mol. Life Sci. 73, 2387–2403.10.1007/s00018-016-2208-zSearch in Google Scholar PubMed

Lalouette, A., Lablack, A., Guenet, J.L., Montagutelli, X., and Segretain, D. (1996). Male sterility caused by sperm cell-specific structural abnormalities in ebouriffe, a new mutation of the house mouse. Biol. Reprod. 55, 355–363.10.1095/biolreprod55.2.355Search in Google Scholar PubMed

Lang, F. and Hoffmann, E.K. (2012). Role of ion transport in control of apoptotic cell death. Compr. Physiol. 2, 2037–2061.10.1002/cphy.c110046Search in Google Scholar PubMed

Lang, F., Busch, G.L., Ritter, M., Volkl, H., Waldegger, S., Gulbins, E., and Haussinger, D. (1998). Functional significance of cell volume regulatory mechanisms. Physiol. Rev. 78, 247–306.10.1152/physrev.1998.78.1.247Search in Google Scholar PubMed

Lang, F., Shumilina, E., Ritter, M., Gulbins, E., Vereninov, A., and Huber, S.M. (2006). Ion channels and cell volume in regulation of cell proliferation and apoptotic cell death. Contrib. Nephrol. 152, 142–160.10.1159/000096321Search in Google Scholar PubMed

Lee, E.L., Shimizu, T., Ise, T., Numata, T., Kohno, K., and Okada, Y. (2007). Impaired activity of volume-sensitive Cl channel is involved in cisplatin resistance of cancer cells. J. Cell. Physiol. 211, 513–521.10.1002/jcp.20961Search in Google Scholar PubMed

Lee, C.C., Freinkman, E., Sabatini, D.M., and Ploegh, H.L. (2014). The protein synthesis inhibitor blasticidin s enters mammalian cells via leucine-rich repeat-containing protein 8D. J. Biol. Chem. 289, 17124–17131.10.1074/jbc.M114.571257Search in Google Scholar PubMed PubMed Central

Levitan, I., Christian, A.E., Tulenko, T.N., and Rothblat, G.H. (2000). Membrane cholesterol content modulates activation of volume-regulated anion current in bovine endothelial cells. J. Gen. Physiol. 115, 405–416.10.1085/jgp.115.4.405Search in Google Scholar PubMed PubMed Central

Liang, W., Huang, L., Zhao, D., He, J.Z., Sharma, P., Liu, J., Gramolini, A.O., Ward, M.E., Cho, H.C., and Backx, P.H. (2014). Swelling-activated Cl- currents and intracellular CLC-3 are involved in proliferation of human pulmonary artery smooth muscle cells. J. Hypertens. 32, 318–330.10.1097/HJH.0000000000000013Search in Google Scholar PubMed

Liu, H.T., Tashmukhamedov, B.A., Inoue, H., Okada, Y., and Sabirov, R.Z. (2006). Roles of two types of anion channels in glutamate release from mouse astrocytes under ischemic or osmotic stress. Glia 54, 343–357.10.1002/glia.20400Search in Google Scholar PubMed

Liu, H.T., Akita, T., Shimizu, T., Sabirov, R.Z., and Okada, Y. (2009). Bradykinin-induced astrocyte-neuron signalling: glutamate release is mediated by ROS-activated volume-sensitive outwardly rectifying anion channels. J. Physiol. 587, 2197–2209.10.1113/jphysiol.2008.165084Search in Google Scholar PubMed PubMed Central

Lück, J.C., Puchkov, D., Ullrich, F., and Jentsch, T.J. (2018). LRRC8/VRAC anion channels are required for late stages of spermatid development in mice. J. Biol. Chem. 293, 11796–11808.10.1074/jbc.RA118.003853Search in Google Scholar PubMed PubMed Central

Lutter, D., Ullrich, F., Lueck, J.C., Kempa, S., and Jentsch, T.J. (2017). Selective transport of neurotransmitters and modulators by distinct volume-regulated LRRC8 anion channels. J. Cell Sci. 130, 1122–1133.10.1242/jcs.196253Search in Google Scholar PubMed

Maeno, E., Ishizaki, Y., Kanaseki, T., Hazama, A., and Okada, Y. (2000). Normotonic cell shrinkage because of disordered volume regulation is an early prerequisite to apoptosis. Proc. Natl. Acad. Sci. U.S.A. 97, 9487–9492.10.1073/pnas.140216197Search in Google Scholar PubMed PubMed Central

Manolopoulos, V.G., Liekens, S., Koolwijk, P., Voets, T., Peters, E., Droogmans, G., Lelkes, P.I., De Clercq, E., and Nilius, B. (2000). Inhibition of angiogenesis by blockers of volume-regulated anion channels. Gen. Pharmacol. 34, 107–116.10.1016/S0306-3623(00)00052-5Search in Google Scholar

Mao, J., Wang, L., Fan, A., Wang, J., Xu, B., Jacob, T.J., and Chen, L. (2007). Blockage of volume-activated chloride channels inhibits migration of nasopharyngeal carcinoma cells. Cell. Physiol. Biochem. 19, 249–258.10.1159/000100644Search in Google Scholar

Miley, H.E., Sheader, E.A., Brown, P.D., and Best, L. (1997). Glucose-induced swelling in rat pancreatic beta-cells. J. Physiol. 504, 191–198.10.1111/j.1469-7793.1997.00191.xSearch in Google Scholar

Miley, H.E., Brown, P.D., and Best, L. (1999). Regulation of a volume-sensitive anion channel in rat pancreatic beta-cells by intracellular adenine nucleotides. J. Physiol. 515, 413–417.10.1111/j.1469-7793.1999.413ac.xSearch in Google Scholar

Min, X.J., Li, H., Hou, S.C., He, W., Liu, J., Hu, B., and Wang, J. (2011). Dysfunction of volume-sensitive chloride channels contributes to cisplatin resistance in human lung adenocarcinoma cells. Exp. Biol. Med. 236, 483–491.10.1258/ebm.2011.010297Search in Google Scholar

Mongin, A.A. (2016). Volume-regulated anion channel – a frenemy within the brain. Pflüger’s Arch. 468, 421–441.10.1007/s00424-015-1765-6Search in Google Scholar

Mongin, A.A. and Kimelberg, H.K. (2002). ATP potently modulates anion channel-mediated excitatory amino acid release from cultured astrocytes. Am. J. Physiol. 283, C569–C578.10.1152/ajpcell.00438.2001Search in Google Scholar

Mongin, A.A. and Orlov, S.N. (2001). Mechanisms of cell volume regulation and possible nature of the cell volume sensor. Pathophysiology 8, 77–88.10.1016/S0928-4680(01)00074-8Search in Google Scholar

Netti, V., Pizzoni, A., Perez-Dominguez, M., Ford, P., Pasantes-Morales, H., Ramos-Mandujano, G., and Capurro, C. (2018). Release of taurine and glutamate contributes to cell volume regulation in human retinal Muller cells: differences in modulation by calcium. J. Neurophysiol. 120, 973–984.10.1152/jn.00725.2017Search in Google Scholar PubMed

Nilius, B. and Droogmans, G. (2001). Ion channels and their functional role in vascular endothelium. Physiol. Rev. 81, 1415–1459.10.1152/physrev.2001.81.4.1415Search in Google Scholar PubMed

Nilius, B., Sehrer, J., Viana, F., De Greef, C., Raeymaekers, L., Eggermont, J., and Droogmans, G. (1994). Volume-activated Cl currents in different mammalian non-excitable cell types. Pflüger’s Arch. 428, 364–371.10.1007/BF00724520Search in Google Scholar

Nilius, B., Eggermont, J., Voets, T., Buyse, G., Manolopoulos, V., and Droogmans, G. (1997a). Properties of volume-regulated anion channels in mammalian cells. Prog. Biophys. Mol. Biol. 68, 69–119.10.1016/S0079-6107(97)00021-7Search in Google Scholar

Nilius, B., Prenen, J., Kamouchi, M., Viana, F., Voets, T., and Droogmans, G. (1997b). Inhibition by mibefradil, a novel calcium channel antagonist, of Ca2+- and volume-activated Cl channels in macrovascular endothelial cells. Br. J. Pharmacol. 121, 547–555.10.1038/sj.bjp.0701140Search in Google Scholar PubMed PubMed Central

Nilius, B., Prenen, J., Voets, T., Eggermont, J., and Droogmans, G. (1998). Activation of volume-regulated chloride currents by reduction of intracellular ionic strength in bovine endothelial cells. J. Physiol. 506, 353–361.10.1111/j.1469-7793.1998.353bw.xSearch in Google Scholar PubMed PubMed Central

Oiki, S., Kubo, M., and Okada, Y. (1994). Mg2+ and ATP-dependence of volume-sensitive Cl channels in human epithelial cells. Jpn. J. Physiol. 44 (Suppl. 2), S77–S79.Search in Google Scholar

Okada, Y., Shimizu, T., Maeno, E., Tanabe, S., Wang, X., and Takahashi, N. (2006). Volume-sensitive chloride channels involved in apoptotic volume decrease and cell death. J. Membr. Biol. 209, 21–29.10.1007/s00232-005-0836-6Search in Google Scholar PubMed

Okada, Y., Sato, K., and Numata, T. (2009). Pathophysiology and puzzles of the volume-sensitive outwardly rectifying anion channel. J. Physiol. 587, 2141–2149.Search in Google Scholar

Okada, T., Islam, M.R., Tsiferova, N.A., Okada, Y., and Sabirov, R.Z. (2017). Specific and essential but not sufficient roles of LRRC8A in the activity of volume-sensitive outwardly rectifying anion channel (VSOR). Channels 11, 109–120.10.1080/19336950.2016.1247133Search in Google Scholar PubMed PubMed Central

Okada, Y., Okada, T., Sato-Numata, K., Islam, M.R., Ando-Akatsuka, Y., Numata, T., Kubo, M., Shimizu, T., Kurbannazarova, R.S., Marunaka, Y., et al. (2019). Cell volume-activated and volume-correlated anion channels in mammalian cells: their biophysical, molecular, and pharmacological properties. Pharmacol. Rev. 71, 49–88.10.1124/pr.118.015917Search in Google Scholar PubMed

Orlov, S.N., Platonova, A.A., Hamet, P., and Grygorczyk, R. (2013). Cell volume and monovalent ion transporters: their role in cell death machinery triggering and progression. Am. J. Physiol. 305, C361–C372.10.1152/ajpcell.00040.2013Search in Google Scholar PubMed

Orre, L.M., Vesterlund, M., Pan, Y., Arslan, T., Zhu, Y., Fernandez Woodbridge, A., Frings, O., Fredlund, E., and Lehtio, J. (2019). SubCellBarCode: proteome-wide mapping of protein localization and relocalization. Mol. Cell. 73, 166–182 e167.10.1016/j.molcel.2018.11.035Search in Google Scholar PubMed

Osei-Owusu, J., Yang, J., Vitery, M.D.C., and Qiu, Z. (2018). Molecular biology and physiology of volume-regulated anion channel (VRAC). Curr. Top. Membr. 81, 177–203.10.1016/bs.ctm.2018.07.005Search in Google Scholar PubMed PubMed Central

Patel, A.J., Lauritzen, I., Lazdunski, M., and Honore, E. (1998). Disruption of mitochondrial respiration inhibits volume-regulated anion channels and provokes neuronal cell swelling. J. Neurosci. 18, 3117–3123.10.1523/JNEUROSCI.18-09-03117.1998Search in Google Scholar

Pedersen, S.F., Hoffmann, E.K., and Mills, J.W. (2001). The cytoskeleton and cell volume regulation. Comp. Biochem. Physiol. A Mol. Integr. Physiol. 130, 385–399.10.1016/S1095-6433(01)00429-9Search in Google Scholar

Pedersen, S.F., Klausen, T.K., and Nilius, B. (2015). The identification of a volume-regulated anion channel: an amazing Odyssey. Acta Physiol. 213, 868–881.10.1111/apha.12450Search in Google Scholar PubMed

Pedersen, S.F., Okada, Y., and Nilius, B. (2016). Biophysics and physiology of the volume-regulated anion channel (VRAC)/volume-sensitive outwardly rectifying anion channel (VSOR). Pflüger’s Arch. 468, 371–383.10.1007/s00424-015-1781-6Search in Google Scholar PubMed

Piepoli, A., Palmieri, O., Maglietta, R., Panza, A., Cattaneo, E., Latiano, A., Laczko, E., Gentile, A., Carella, M., Mazzoccoli, G., et al. (2012). The expression of leucine-rich repeat gene family members in colorectal cancer. Exp. Biol. Med. 237, 1123–1128.10.1258/ebm.2012.012042Search in Google Scholar PubMed

Planells-Cases, R., Lutter, D., Guyader, C., Gerhards, N.M., Ullrich, F., Elger, D.A., Kucukosmanoglu, A., Xu, G., Voss, F.K., Reincke, S.M., et al. (2015). Subunit composition of VRAC channels determines substrate specificity and cellular resistance to Pt-based anti-cancer drugs. EMBO J. 34, 2993–3008.10.15252/embj.201592409Search in Google Scholar PubMed PubMed Central

Platt, C.D., Chou, J., Houlihan, P., Badran, Y.R., Kumar, L., Bainter, W., Poliani, P.L., Perez, C.J., Dent, S.Y.R., Clapham, D.E., et al. (2017). Leucine-rich repeat containing 8A (LRRC8A)-dependent volume-regulated anion channel activity is dispensable for T-cell development and function. J. Allergy Clin. Immunol. 140, 1651–1659 e1651.10.1016/j.jaci.2016.12.974Search in Google Scholar PubMed PubMed Central

Poletto Chaves, L.A. and Varanda, W.A. (2008). Volume-activated chloride channels in mice Leydig cells. Pflüger’s Arch. 457, 493–504.10.1007/s00424-008-0525-2Search in Google Scholar PubMed

Poulsen, K.A., Andersen, E.C., Hansen, C.F., Klausen, T.K., Hougaard, C., Lambert, I.H., and Hoffmann, E.K. (2010). Deregulation of apoptotic volume decrease and ionic movements in multidrug-resistant tumor cells: role of chloride channels. Am. J. Physiol. 298, C14–C25.10.1152/ajpcell.00654.2008Search in Google Scholar PubMed

Prager-Khoutorsky, M. and Bourque, C.W. (2015). Mechanical basis of osmosensory transduction in magnocellular neurosecretory neurones of the rat supraoptic nucleus. J. Neuroendocrinol. 27, 507–515.10.1111/jne.12270Search in Google Scholar PubMed

Qiu, Z., Dubin, A.E., Mathur, J., Tu, B., Reddy, K., Miraglia, L.J., Reinhardt, J., Orth, A.P., and Patapoutian, A. (2014). SWELL1, a plasma membrane protein, is an essential component of volume-regulated anion channel. Cell 157, 447–458.10.1016/j.cell.2014.03.024Search in Google Scholar

Roman, R.M., Bodily, K.O., Wang, Y., Raymond, J.R., and Fitz, J.G. (1998). Activation of protein kinase Calpha couples cell volume to membrane Cl permeability in HTC hepatoma and Mz-ChA-1 cholangiocarcinoma cells. Hepatology 28, 1073–1080.10.1002/hep.510280423Search in Google Scholar

Rorsman, P. and Braun, M. (2013). Regulation of insulin secretion in human pancreatic islets. Annu. Rev. Physiol. 75, 155–179.10.1146/annurev-physiol-030212-183754Search in Google Scholar

Roy, G. (1995). Amino acid current through anion channels in cultured human glial cells. J. Membr. Biol. 147, 35–44.10.1007/BF00235396Search in Google Scholar

Rubino, S., Bach, M.D., Schober, A.L., Lambert, I.H., and Mongin, A.A. (2018). Downregulation of leucine-rich repeat-containing 8A limits proliferation and increases sensitivity of glioblastoma to temozolomide and carmustine. Front. Oncol. 8, 142.10.3389/fonc.2018.00142Search in Google Scholar

Rudkouskaya, A., Chernoguz, A., Haskew-Layton, R.E., and Mongin, A.A. (2008). Two conventional protein kinase C isoforms, alpha and beta I, are involved in the ATP-induced activation of volume-regulated anion channel and glutamate release in cultured astrocytes. J. Neurochem. 105, 2260–2270.10.1111/j.1471-4159.2008.05312.xSearch in Google Scholar

Sabirov, R.Z., Prenen, J., Tomita, T., Droogmans, G., and Nilius, B. (2000). Reduction of ionic strength activates single volume-regulated anion channels (VRAC) in endothelial cells. Pflüger’s Arch. 439, 315–320.10.1007/s004249900186Search in Google Scholar

Sato-Numata, K., Numata, T., Inoue, R., Sabirov, R.Z., and Okada, Y. (2017). Distinct contributions of LRRC8A and its paralogs to the VSOR anion channel from those of the ASOR anion channel. Channels 11, 167–172.10.1080/19336950.2016.1230574Search in Google Scholar

Sawada, A., Takihara, Y., Kim, J.Y., Matsuda-Hashii, Y., Tokimasa, S., Fujisaki, H., Kubota, K., Endo, H., Onodera, T., Ohta, H., et al. (2003). A congenital mutation of the novel gene LRRC8 causes agammaglobulinemia in humans. J. Clin. Invest. 112, 1707–1713.10.1172/JCI18937Search in Google Scholar

Schlichter, L.C., Sakellaropoulos, G., Ballyk, B., Pennefather, P.S., and Phipps, D.J. (1996). Properties of K+ and Cl channels and their involvement in proliferation of rat microglial cells. Glia 17, 225–236.10.1002/(SICI)1098-1136(199607)17:3<225::AID-GLIA5>3.0.CO;2-#Search in Google Scholar

Schober, A.L., Wilson, C.S., and Mongin, A.A. (2017). Molecular composition and heterogeneity of the LRRC8-containing swelling-activated osmolyte channels in primary rat astrocytes. J. Physiol. 595, 6939–6951.10.1113/JP275053Search in Google Scholar PubMed PubMed Central

Schumacher, P.A., Sakellaropoulos, G., Phipps, D.J., and Schlichter, L.C. (1995). Small-conductance chloride channels in human peripheral T lymphocytes. J. Membr. Biol. 145, 217–232.10.1007/BF00232714Search in Google Scholar PubMed

Schwab, A., Fabian, A., Hanley, P.J., and Stock, C. (2012). Role of ion channels and transporters in cell migration. Physiol. Rev. 92, 1865–1913.10.1152/physrev.00018.2011Search in Google Scholar PubMed

Shimizu, T., Numata, T., and Okada, Y. (2004). A role of reactive oxygen species in apoptotic activation of volume-sensitive Cl channel. Proc. Natl. Acad. Sci. USA. 101, 6770–6773.10.1073/pnas.0401604101Search in Google Scholar PubMed PubMed Central

Shimizu, T., Ohtake, H., Fujii, T., Tabuchi, Y., and Sakai, H. (2015). Volume-sensitive outwardly rectifying Cl channels contribute to butyrate-triggered apoptosis of murine colonic epithelial MCE301 cells. J. Physiol. Sci. 65, 151–157.10.1007/s12576-014-0352-5Search in Google Scholar PubMed

Sirianant, L., Wanitchakool, P., Ousingsawat, J., Benedetto, R., Zormpa, A., Cabrita, I., Schreiber, R., and Kunzelmann, K. (2016). Non-essential contribution of LRRC8A to volume regulation. Pflüger’s Arch. 468, 805–816.10.1007/s00424-016-1789-6Search in Google Scholar PubMed

Sørensen, B.H., Thorsteinsdottir, U.A., and Lambert, I.H. (2014). Acquired cisplatin resistance in human ovarian A2780 cancer cells correlates with shift in taurine homeostasis and ability to volume regulate. Am. J. Physiol. 307, C1071–C1080.10.1152/ajpcell.00274.2014Search in Google Scholar PubMed

Sørensen, B.H., Dam, C.S., Sturup, S., and Lambert, I.H. (2016a). Dual role of LRRC8A-containing transporters on cisplatin resistance in human ovarian cancer cells. J. Inorg. Biochem. 160, 287–295.10.1016/j.jinorgbio.2016.04.004Search in Google Scholar PubMed

Sørensen, B.H., Nielsen, D., Thorsteinsdottir, U.A., Hoffmann, E.K., and Lambert, I.H. (2016b). Downregulation of LRRC8A protects human ovarian and alveolar carcinoma cells against Cisplatin-induced expression of p53, MDM2, p21Waf1/Cip1, and caspase-9/-3 activation. Am. J. Physiol. 310, C857–C873.10.1152/ajpcell.00256.2015Search in Google Scholar PubMed PubMed Central

Soroceanu, L., Manning, T.J., Jr., and Sontheimer, H. (1999). Modulation of glioma cell migration and invasion using Cl and K+ ion channel blockers. J. Neurosci. 19, 5942–5954.10.1523/JNEUROSCI.19-14-05942.1999Search in Google Scholar

Stauber, T. (2015). The volume-regulated anion channel is formed by LRRC8 heteromers – molecular identification and roles in membrane transport and physiology. Biol. Chem. 396, 975–990.10.1515/hsz-2015-0127Search in Google Scholar PubMed

Strange, K., Emma, F., and Jackson, P.S. (1996). Cellular and molecular physiology of volume-sensitive anion channels. Am. J. Physiol. 270, C711–C730.10.1152/ajpcell.1996.270.3.C711Search in Google Scholar PubMed

Strange, K., Yamada, T., and Denton, J.S. (2019). A 30-year journey from volume-regulated anion currents to molecular structure of the LRRC8 channel. J. Gen. Physiol. 151, 100–117.10.1085/jgp.201812138Search in Google Scholar PubMed PubMed Central

Stroka, K.M., Jiang, H., Chen, S.H., Tong, Z., Wirtz, D., Sun, S.X., and Konstantopoulos, K. (2014). Water permeation drives tumor cell migration in confined microenvironments. Cell 157, 611–623.10.1016/j.cell.2014.02.052Search in Google Scholar PubMed PubMed Central

Stuhlmann, T., Planells-Cases, R., and Jentsch, T.J. (2018). LRRC8/VRAC anion channels enhance beta-cell glucose sensing and insulin secretion. Nat. Commun. 9, 1974.10.1038/s41467-018-04353-ySearch in Google Scholar PubMed PubMed Central

Syeda, R., Qiu, Z., Dubin, A.E., Murthy, S.E., Florendo, M.N., Mason, D.E., Mathur, J., Cahalan, S.M., Peters, E.C., Montal, M., et al. (2016). LRRC8 proteins form volume-regulated anion channels that sense ionic strength. Cell 164, 499–511.10.1016/j.cell.2015.12.031Search in Google Scholar PubMed PubMed Central

Thorsteinsdottir, U.A., Thorsteinsdottir, M., and Lambert, I.H. (2016). Protolichesterinic acid, isolated from the lichen Cetraria islandica, reduces LRRC8A Expression and volume-sensitive release of organic osmolytes in human lung epithelial cancer cells. Phytother. Res. 30, 97–104.10.1002/ptr.5507Search in Google Scholar PubMed

Tilly, B.C., Edixhoven, M.J., Tertoolen, L.G., Morii, N., Saitoh, Y., Narumiya, S., and de Jonge, H.R. (1996). Activation of the osmo-sensitive chloride conductance involves P21rho and is accompanied by a transient reorganization of the F-actin cytoskeleton. Mol. Biol. Cell. 7, 1419–1427.10.1091/mbc.7.9.1419Search in Google Scholar PubMed PubMed Central

Tominaga, K., Kondo, C., Kagata, T., Hishida, T., Nishizuka, M., and Imagawa, M. (2004). The novel gene fad158, having a transmembrane domain and leucine-rich repeat, stimulates adipocyte differentiation. J. Biol. Chem. 279, 34840–34848.10.1074/jbc.M312927200Search in Google Scholar PubMed

Trothe, J., Ritzmann, D., Lang, V., Scholz, P., Pul, U., Kaufmann, R., Buerger, C., and Ertongur-Fauth, T. (2018). Hypotonic stress response of human keratinocytes involves LRRC8A as component of volume-regulated anion channels. Exp. Dermatol. 27, 1352–1360.10.1111/exd.13789Search in Google Scholar PubMed

Trouet, D., Nilius, B., Jacobs, A., Remacle, C., Droogmans, G., and Eggermont, J. (1999). Caveolin-1 modulates the activity of the volume-regulated chloride channel. J. Physiol. 520, 113–119.10.1111/j.1469-7793.1999.t01-1-00113.xSearch in Google Scholar PubMed PubMed Central

Ullrich, F., Reincke, S.M., Voss, F.K., Stauber, T., and Jentsch, T.J. (2016). Inactivation and anion selectivity of volume-regulated anion channels (VRACs) depend on C-terminal residues of the first extracellular loop. J. Biol. Chem. 291, 17040–17048.10.1074/jbc.M116.739342Search in Google Scholar PubMed PubMed Central

Vakili, A., Hosseinzadeh, S.A., and Khorasani, M.Z. (2009). Peripheral administration of carbenoxolone reduces ischemic reperfusion injury in transient model of cerebral ischemia. J. Stroke Cerebrovasc. Dis. 18, 81–85.10.1016/j.jstrokecerebrovasdis.2008.09.018Search in Google Scholar PubMed

Varela, D., Simon, F., Riveros, A., Jorgensen, F., and Stutzin, A. (2004). NAD(P)H oxidase-derived H2O2 signals chloride channel activation in cell volume regulation and cell proliferation. J. Biol. Chem. 279, 13301–13304.10.1074/jbc.C400020200Search in Google Scholar PubMed

Voets, T., Szucs, G., Droogmans, G., and Nilius, B. (1995). Blockers of volume-activated Cl currents inhibit endothelial cell proliferation. Pflüger’s Arch. 431, 132–134.10.1007/BF00374387Search in Google Scholar PubMed

Voets, T., Manolopoulos, V., Eggermont, J., Ellory, C., Droogmans, G., and Nilius, B. (1998). Regulation of a swelling-activated chloride current in bovine endothelium by protein tyrosine phosphorylation and G proteins. J. Physiol. 506, 341–352.10.1111/j.1469-7793.1998.341bw.xSearch in Google Scholar PubMed PubMed Central

Voets, T., Droogmans, G., Raskin, G., Eggermont, J., and Nilius, B. (1999). Reduced intracellular ionic strength as the initial trigger for activation of endothelial volume-regulated anion channels. Proc. Natl. Acad. Sci. USA. 96, 5298–5303.10.1073/pnas.96.9.5298Search in Google Scholar PubMed PubMed Central

Voss, F.K., Ullrich, F., Münch, J., Lazarow, K., Lutter, D., Mah, N., Andrade-Navarro, M.A., von Kries, J.P., Stauber, T., and Jentsch, T.J. (2014). Identification of LRRC8 heteromers as an essential component of the volume-regulated anion channel VRAC. Science 344, 634–638.10.1126/science.1252826Search in Google Scholar PubMed

Wang, R., Lu, Y., Gunasekar, S., Zhang, Y., Benson, C.J., Chapleau, M.W., Sah, R., and Abboud, F.M. (2017). The volume-regulated anion channel (LRRC8) in nodose neurons is sensitive to acidic pH. JCI Insight 2, e90632.10.1172/jci.insight.90632Search in Google Scholar PubMed PubMed Central

Wang, Y., Ren, F., Chen, P., Liu, S., Song, Z., and Ma, X. (2018). Identification of a six-gene signature with prognostic value for patients with endometrial carcinoma. Cancer Med. 7, 5632–5642.10.1002/cam4.1806Search in Google Scholar PubMed PubMed Central

Wong, R., Chen, W., Zhong, X., Rutka, J.T., Feng, Z.P., and Sun, H.S. (2018). Swelling-induced chloride current in glioblastoma proliferation, migration, and invasion. J. Cell. Physiol. 233, 363–370.10.1002/jcp.25891Search in Google Scholar PubMed

Xia, Y., Liu, Y., Xia, T., Li, X., Huo, C., Jia, X., Wang, L., Xu, R., Wang, N., Zhang, M., et al. (2016). Activation of volume-sensitive Cl channel mediates autophagy-related cell death in myocardial ischaemia/reperfusion injury. Oncotarget 7, 39345–39362.10.18632/oncotarget.10050Search in Google Scholar PubMed PubMed Central

Xiao, G.S., Zhang, Y.H., Wang, Y., Sun, H.Y., Baumgarten, C.M., and Li, G.R. (2018). Noradrenaline up-regulates volume-regulated chloride current by PKA-independent cAMP/exchange protein activated by cAMP pathway in human atrial myocytes. Br. J. Pharmacol. 175, 3422–3432.10.1111/bph.14392Search in Google Scholar PubMed PubMed Central

Xie, L., Zhang, Y., Gunasekar, S.K., Mishra, A., Cao, L., and Sah, R. (2017). Induction of adipose and hepatic SWELL1 expression is required for maintaining systemic insulin-sensitivity in obesity. Channels 11, 673–677.10.1080/19336950.2017.1373225Search in Google Scholar PubMed PubMed Central

Xue, Y., Li, H., Zhang, Y., Han, X., Zhang, G., Li, W., Zhang, H., Lin, Y., Chen, P., Sun, X., et al. (2018). Natural and synthetic flavonoids, novel blockers of the volume-regulated anion channels, inhibit endothelial cell proliferation. Pflüger’s Arch. 470, 1473–1483.10.1007/s00424-018-2170-8Search in Google Scholar PubMed

Yamada, T. and Strange, K. (2018). Intracellular and extracellular loops of LRRC8 are essential for volume-regulated anion channel function. J. Gen. Physiol. 150, 1003–1015.10.1085/jgp.201812016Search in Google Scholar PubMed PubMed Central

Yamada, T., Wondergem, R., Morrison, R., Yin, V.P., and Strange, K. (2016). Leucine-rich repeat containing protein LRRC8A is essential for swelling-activated Cl currents and embryonic development in zebrafish. Physiol. Rep. 4, e12940.10.14814/phy2.12940Search in Google Scholar PubMed PubMed Central

Yamamoto, S., Ichishima, K., and Ehara, T. (2008). Regulation of volume-regulated outwardly rectifying anion channels by phosphatidylinositol 3,4,5-trisphosphate in mouse ventricular cells. Biomed. Res. 29, 307–315.10.2220/biomedres.29.307Search in Google Scholar PubMed

Yang, C., He, L., Chen, G., Ning, Z., and Xia, Z. (2019a). LRRC8A potentiates temozolomide sensitivity in glioma cells via activating mitochondria-dependent apoptotic pathway. Hum. Cell 32, 41–50.10.1007/s13577-018-0221-2Search in Google Scholar PubMed

Yang, J., Vitery, M.D.C., Chen, J., Osei-Owusu, J., Chu, J., and Qiu, Z. (2019b). Glutamate-releasing SWELL1 channel in astrocytes modulates synaptic transmission and promotes brain damage in stroke. Neuron. 102, 813–827.10.1016/j.neuron.2019.03.029Search in Google Scholar PubMed PubMed Central

Yeung, C.H., Barfield, J.P., and Cooper, T.G. (2006). Physiological volume regulation by spermatozoa. Mol. Cell. Endocrinol. 250, 98–105.10.1016/j.mce.2005.12.030Search in Google Scholar PubMed

Zhang, Y., Zhang, H., Feustel, P.J., and Kimelberg, H.K. (2008). DCPIB, a specific inhibitor of volume regulated anion channels (VRACs), reduces infarct size in MCAo and the release of glutamate in the ischemic cortical penumbra. Exp. Neurol. 210, 514–520.10.1016/j.expneurol.2007.11.027Search in Google Scholar PubMed PubMed Central

Zhang, Y., Xie, L., Gunasekar, S.K., Tong, D., Mishra, A., Gibson, W.J., Wang, C., Fidler, T., Marthaler, B., Klingelhutz, A., et al. (2017). SWELL1 is a regulator of adipocyte size, insulin signalling and glucose homeostasis. Nat. Cell Biol. 19, 504–517.10.1038/ncb3514Search in Google Scholar PubMed PubMed Central

Zhang, H., Deng, Z., Zhang, D., Li, H., Zhang, L., Niu, J., Zuo, W., Fu, R., Fan, L., Ye, J.H., et al. (2018). High expression of leucinerich repeat containing 8A is indicative of a worse outcome of colon cancer patients by enhancing cancer cell growth and metastasis. Oncol. Rep. 40, 1275–1286.Search in Google Scholar

Zholos, A., Beck, B., Sydorenko, V., Lemonnier, L., Bordat, P., Prevarskaya, N., and Skryma, R. (2005). Ca2+- and volume-sensitive chloride currents are differentially regulated by agonists and store-operated Ca2+ entry. J. Gen. Physiol. 125, 197–211.10.1085/jgp.200409161Search in Google Scholar PubMed PubMed Central

Received: 2019-03-12
Accepted: 2019-04-27
Published Online: 2019-08-24
Published in Print: 2019-11-26

©2019 Walter de Gruyter GmbH, Berlin/Boston

Downloaded on 9.12.2023 from https://www.degruyter.com/document/doi/10.1515/hsz-2019-0189/html
Scroll to top button