{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,12]],"date-time":"2026-07-12T03:12:42Z","timestamp":1783825962084,"version":"3.55.0"},"reference-count":56,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2022,6,9]],"date-time":"2022-06-09T00:00:00Z","timestamp":1654732800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["P30\u2010EY\u2010011374"],"award-info":[{"award-number":["P30\u2010EY\u2010011374"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["R01\u2010EY\u2010026514"],"award-info":[{"award-number":["R01\u2010EY\u2010026514"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["R01\u2010EY\u2010026882"],"award-info":[{"award-number":["R01\u2010EY\u2010026882"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Glia"],"published-print":{"date-parts":[[2022,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Volume transmission plays an essential role in CNS function, with neurotransmitters released from synapses diffusing through the extracellular space (ECS) to distant sites. Changes in the ECS volume fraction (<jats:italic>\u03b1<\/jats:italic>) will influence the diffusion and the concentration of transmitters within the ECS. We have recently shown that neuronal activity evoked by physiological photic stimuli results in rapid decreases in ECS<jats:italic>\u03b1<\/jats:italic>as large as 10% in the retina. We now characterize the cellular mechanisms responsible for this ECS shrinkage. We find that block of inwardly rectifying K<jats:sup>+<\/jats:sup>channels with Ba<jats:sup>2+<\/jats:sup>, inhibition of the Na<jats:sup>+<\/jats:sup>\/K<jats:sup>+<\/jats:sup>\/2Cl<jats:sup>\u2212<\/jats:sup>cotransporter with bumetanide, or block of AQP4 water channels with TGN\u2010020 do not diminish the light\u2010evoked ECS decrease. Inhibition of the Na<jats:sup>+<\/jats:sup>\/HCO<jats:sub>3<\/jats:sub><jats:sup>\u2212<\/jats:sup>cotransporter by removing HCO<jats:sub>3<\/jats:sub><jats:sup>\u2212<\/jats:sup>from the superfusate, in contrast, reduces the light\u2010evoked ECS decrease by 95.6%. Inhibition of the monocarboxylate transporter with alpha\u2010cyano\u20104\u2010hydroxycinnamate (4\u2010CIN) also reduces the ECS shrinkage, but only by 32.5%. We tested whether the swelling of M\u00fcller cells, the principal glial cells of the retina, is responsible for the light\u2010evoked ECS shrinkage. Light stimulation evoked a 6.3% increase in the volume of the fine processes of M\u00fcller cells. This volume increase was reduced by 97.1% when HCO<jats:sub>3<\/jats:sub><jats:sup>\u2212<\/jats:sup>was removed from the superfusate. We conclude that a large fraction of the activity\u2010dependent decrease in ECS<jats:italic>\u03b1<\/jats:italic>is generated by the activation of the Na<jats:sup>+<\/jats:sup>\/HCO<jats:sub>3<\/jats:sub><jats:sup>\u2212<\/jats:sup>cotransporter in M\u00fcller cells. The monocarboxylate transporter may also contribute to the response.<\/jats:p>","DOI":"10.1002\/glia.24228","type":"journal-article","created":{"date-parts":[[2022,6,9]],"date-time":"2022-06-09T13:13:37Z","timestamp":1654780417000},"page":"1927-1937","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Cellular mechanisms mediating activity\u2010dependent extracellular space shrinkage in the retina"],"prefix":"10.1002","volume":"70","author":[{"given":"Pei\u2010Pei","family":"Chiang","sequence":"first","affiliation":[{"name":"Department of Neuroscience University of Minnesota Minneapolis Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sidney P.","family":"Kuo","sequence":"additional","affiliation":[{"name":"Department of Neuroscience University of Minnesota Minneapolis Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9296-6237","authenticated-orcid":false,"given":"Eric A.","family":"Newman","sequence":"additional","affiliation":[{"name":"Department of Neuroscience University of Minnesota Minneapolis Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,6,9]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(98)00427-8"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn2759"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2009.03.015"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.2001.281.5.F920"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0707667"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.22-06-02165.2002"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP281544"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.272.5265.1182"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(98)00699-X"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)61561-3"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.22319"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.21205"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2020.08.030"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2007.12.040"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.17-20-07725.1997"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0024892"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.20-15-05733.2000"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/0042-6989(93)90098-H"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1717-20.2020"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.22629"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.23187"},{"key":"e_1_2_9_23_1","first-page":"619","article-title":"Ionic changes and alterations in the size of the extracellular space during epileptic activity","volume":"44","author":"Lux H. D.","year":"1986","journal-title":"Advances in Neurology"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.23824"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41583-021-00454-8"},{"issue":"1","key":"e_1_2_9_26_1","doi-asserted-by":"crossref","first-page":"S85","DOI":"10.33549\/physiolres.930000.51.S85","article-title":"Changes in extracellular space volume and geometry induced by cortical spreading depression in immature and adult rats","volume":"51","author":"Mazel T.","year":"2002","journal-title":"Physiological Research"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1098\/rstb.2014.0047"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2006.09.014"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2186-10.2010"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2004.08.053"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.18-07-02506.1998"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/0166-2236(96)10040-0"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.05-08-02225.1985"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(89)91109-8"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.11-12-03972.1991"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.16-01-00159.1996"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-1136(199906)26:4<302::AID-GLIA4>3.0.CO;2-A"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.23-05-01659.2003"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.440040411"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpj.2017.06.052"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.17-01-00171.1997"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1002\/1097-4547(20001115)62:4<530::AID-JNR7>3.0.CO;2-7"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.05-02-00532.1985"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5320(72)90095-0"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.physiol.61.1.699"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2006.05.015"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2007.09.008"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(91)91235-S"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2004.06.077"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00027.2007"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2377-13.2014"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.23851"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2005.09.002"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0952523809990137"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.20-20-07657.2000"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1023\/B:DOOP.0000019487.88486.0a"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00288.2007"}],"container-title":["Glia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/glia.24228","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/glia.24228","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/glia.24228","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,9,26]],"date-time":"2024-09-26T18:18:45Z","timestamp":1727374725000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/glia.24228"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,9]]},"references-count":56,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2022,10]]}},"alternative-id":["10.1002\/glia.24228"],"URL":"https:\/\/doi.org\/10.1002\/glia.24228","archive":["Portico"],"relation":{},"ISSN":["0894-1491","1098-1136"],"issn-type":[{"value":"0894-1491","type":"print"},{"value":"1098-1136","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,9]]},"assertion":[{"value":"2022-02-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-05-26","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-06-09","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}