{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T01:07:59Z","timestamp":1776128879901,"version":"3.50.1"},"reference-count":62,"publisher":"American Physiological Society","issue":"2","funder":[{"DOI":"10.13039\/100000053","name":"HHS | NIH | National Eye Institute","doi-asserted-by":"publisher","award":["R21EY026176"],"award-info":[{"award-number":["R21EY026176"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000053","name":"HHS | NIH | National Eye Institute","doi-asserted-by":"publisher","award":["RO1EY027729"],"award-info":[{"award-number":["RO1EY027729"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000053","name":"HHS | NIH | National Eye Institute","doi-asserted-by":"publisher","award":["P30EY08126"],"award-info":[{"award-number":["P30EY08126"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000053","name":"HHS | NIH | National Eye Institute","doi-asserted-by":"publisher","award":["T32EY007135"],"award-info":[{"award-number":["T32EY007135"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000053","name":"HHS | NIH | National Eye Institute","doi-asserted-by":"publisher","award":["P30EY08126"],"award-info":[{"award-number":["P30EY08126"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Research to Prevent Blindness, Inc.","award":["Unrestricted Departmental Award"],"award-info":[{"award-number":["Unrestricted Departmental Award"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Cell Physiology"],"published-print":{"date-parts":[[2019,8,1]]},"abstract":"<jats:p> Glaucoma is the leading cause of blindness worldwide, resulting from degeneration of retinal ganglion cells (RGCs), which form the optic nerve. Prior to structural degeneration, RGCs exhibit physiological deficits. M\u00fcller glia provide homeostatic regulation of ions that supports RGC physiology through a process called K<jats:sup>+<\/jats:sup> siphoning. Recent studies suggest that several retinal conditions, including glaucoma, involve changes in the expression of K<jats:sup>+<\/jats:sup> channels in M\u00fcller glia. To clarify whether glaucoma-related stressors directly alter expression and function of K<jats:sup>+<\/jats:sup> channels in M\u00fcller glia, we examined changes in the expression of inwardly rectifying K<jats:sup>+<\/jats:sup> (Kir) channels and two-pore domain (K2P) channels in response to elevated intraocular pressure (IOP) in vivo and in vitro in primary cultures of M\u00fcller glia exposed to elevated hydrostatic pressure. We then measured outcomes of cell health, cation homeostasis, and cation flux in M\u00fcller glia cultures. Transcriptome analysis in a murine model of microbead-induced glaucoma revealed pressure-dependent downregulation of Kir and K2P channels in vivo. Changes in the expression and localization of Kir and K2P channels in response to elevated pressure were also found in M\u00fcller glia in vitro. Finally, we found that elevated pressure compromises the plasma membrane of M\u00fcller glia and induces cation dyshomeostasis that involves changes in ion flux through cation channels. Pressure-induced changes in cation flux precede both cation dyshomeostasis and membrane compromise. Our findings have implications for M\u00fcller glia responses to pressure-related conditions, i.e., glaucoma, and identify cation dyshomeostasis as a potential contributor to electrophysiological impairment observed in RGCs of glaucomatous retina. <\/jats:p>","DOI":"10.1152\/ajpcell.00444.2018","type":"journal-article","created":{"date-parts":[[2019,6,5]],"date-time":"2019-06-05T18:42:50Z","timestamp":1559760170000},"page":"C375-C389","source":"Crossref","is-referenced-by-count":13,"title":["Pressure-dependent modulation of inward-rectifying K<sup>+<\/sup> channels: implications for cation homeostasis and K<sup>+<\/sup> dynamics in glaucoma"],"prefix":"10.1152","volume":"317","author":[{"given":"Rachel A.","family":"Fischer","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abigail L.","family":"Roux","sequence":"additional","affiliation":[{"name":"Vanderbilt Eye Institute, Vanderbilt University Medical Center, Nashville, Tennessee"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lauren K.","family":"Wareham","sequence":"additional","affiliation":[{"name":"Vanderbilt Eye Institute, Vanderbilt University Medical Center, Nashville, Tennessee"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3136-9631","authenticated-orcid":false,"given":"Rebecca M.","family":"Sappington","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee"},{"name":"Vanderbilt Eye Institute, Vanderbilt University Medical Center, Nashville, Tennessee"},{"name":"Department of Ophthalmology and Visual Sciences, Vanderbilt University School of Medicine, Nashville, Tennessee"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1007\/s00417-008-0872-x"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-1136(20000101)29:1<35:AID-GLIA4>3.0.CO;2-A"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1111\/j.1582-4934.2006.tb00289.x"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2012.07.001"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1201132109"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.14-15691"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2004.03553.x"},{"key":"B8","first-page":"1","volume":"291","author":"Choi JS","year":"1999","journal-title":"J Pharmacol Exp Ther"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2010.12.036"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0913141107"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/S0028-3908(99)00206-3"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1097\/00001756-200402090-00022"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1002\/glia.21139"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2017.00318"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.4172\/2155-9899.1000439"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1419-14.2015"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00029.2009"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2014.287268"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.73.4.1907-1916.2005"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1002\/adhm.201701290"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.4172\/2155-9899.1000188"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.119.3.493"},{"key":"B23","first-page":"1945","volume":"53","author":"Gorczyca W","year":"1993","journal-title":"Cancer Res"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-2999(98)00955-8"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2010.09.001"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1038\/srep46085"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.18-21-08936.1998"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1291-12.2012"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2003.12.104"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0706068"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1016\/j.vascn.2004.06.003"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1002\/glia.10112"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2004.06.008"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.4172\/2155-9570.1000491"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.398164"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcn.2012.01.002"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-007-0377-1"},{"key":"B38","first-page":"2423","volume":"7","author":"Newman EA","year":"1987","journal-title":"J Neurosci"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1126\/science.6474173"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2007.08.018"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1419921112"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.55.03.06.db05-1349"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcn.2013.08.002"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1152\/physiolgenomics.00006.2005"},{"key":"B45","first-page":"83","volume":"38","author":"Quigley HA","year":"1997","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1097\/00001756-200206120-00012"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1002\/glia.22477"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e13-10-0592"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-007-0313-4"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1714888115"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1962-08.2008"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.07-1355"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.05-1408"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.09-3947"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.05-1407"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.08-2321"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M212243200"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1124\/mol.105.020842"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2018.09.002"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1177\/1087057104268749"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1038\/srep11294"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2011.10.011"}],"container-title":["American Journal of Physiology-Cell Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.physiology.org\/doi\/pdf\/10.1152\/ajpcell.00444.2018","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,17]],"date-time":"2024-06-17T15:39:56Z","timestamp":1718638796000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.physiology.org\/doi\/10.1152\/ajpcell.00444.2018"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,8,1]]},"references-count":62,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2019,8,1]]}},"alternative-id":["10.1152\/ajpcell.00444.2018"],"URL":"https:\/\/doi.org\/10.1152\/ajpcell.00444.2018","relation":{},"ISSN":["0363-6143","1522-1563"],"issn-type":[{"value":"0363-6143","type":"print"},{"value":"1522-1563","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,8,1]]}}}