{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T08:12:18Z","timestamp":1770883938325,"version":"3.50.1"},"reference-count":56,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2012,3,19]],"date-time":"2012-03-19T00:00:00Z","timestamp":1332115200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Glia"],"published-print":{"date-parts":[[2012,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Increased ammonium (NH<jats:sub>4<\/jats:sub>\n<jats:sup>+<\/jats:sup>) concentration in the brain is the prime candidate responsible for hepatic encephalopathy (HE), a serious neurological disorder caused by liver failure and characterized by disturbed glutamatergic neurotransmission and impaired glial function. We investigated the mechanisms of NH<jats:sub>4<\/jats:sub>\n<jats:sup>+<\/jats:sup>\u2010induced depolarization of astrocytes in mouse hippocampal slices using whole\u2010cell patch\u2010clamp and potassium\u2010selective microelectrodes. At postnatal days (P) 18\u201321, perfusion with 5 mM NH<jats:sub>4<\/jats:sub>\n<jats:sup>+<\/jats:sup> evoked a transient increase in the extracellular potassium concentration ([K<jats:sup>+<\/jats:sup>]<jats:sub>o<\/jats:sub>) by about 1 mM. Astrocytes depolarized by on average 8 mV and then slowly repolarized to a plateau depolarization of 6 mV, which was maintained during NH<jats:sub>4<\/jats:sub>\n<jats:sup>+<\/jats:sup> perfusion. In voltage\u2010clamped astrocytes, NH<jats:sub>4<\/jats:sub>\n<jats:sup>+<\/jats:sup> induced an inward current and a reduction in membrane resistance. Amplitudes of [K<jats:sup>+<\/jats:sup>]<jats:sub>o<\/jats:sub> transients and astrocyte depolarization\/inward currents increased from P3\u20134 to P18\u201321. Perfusion with 100 \u03bcM Ba<jats:sup>2+<\/jats:sup> did not alter [K<jats:sup>+<\/jats:sup>]<jats:sub>o<\/jats:sub> transients but strongly reduced both astrocyte depolarization and inward currents. NH<jats:sub>4<\/jats:sub>\n<jats:sup>+<\/jats:sup>\u2010induced depolarization and inward currents were also virtually absent in slices from Kir4.1 \u2212\/\u2212 mice, while [K<jats:sup>+<\/jats:sup>]<jats:sub>o<\/jats:sub> transients were unaltered. Blocking Na<jats:sup>+<\/jats:sup>\/K<jats:sup>+<\/jats:sup>\u2010ATPase with ouabain caused an immediate and complex increase in [K<jats:sup>+<\/jats:sup>]<jats:sub>o<\/jats:sub>. Taken together, our results are in agreement with the hypothesis that reduced uptake of K<jats:sup>+<\/jats:sup> by the Na<jats:sup>+<\/jats:sup>, K<jats:sup>+<\/jats:sup>\u2010ATPase in the presence of NH<jats:sub>4<\/jats:sub>\n<jats:sup>+<\/jats:sup> disturbs the extracellular K<jats:sup>+<\/jats:sup> homeostasis. Furthermore, astrocytes depolarize in response to the increase in [K<jats:sup>+<\/jats:sup>]<jats:sub>o<\/jats:sub> and by influx of NH<jats:sub>4<\/jats:sub>\n<jats:sup>+<\/jats:sup> through Kir4.1 channels. The depolarization reduces the astrocytes' capacity for channel\u2010mediated flux of K<jats:sup>+<\/jats:sup> and for uptake of glutamate and might hereby contribute to the pathology of HE. \u00a9 2012 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/glia.22328","type":"journal-article","created":{"date-parts":[[2012,3,19]],"date-time":"2012-03-19T18:50:50Z","timestamp":1332183050000},"page":"965-978","source":"Crossref","is-referenced-by-count":40,"title":["Kir4.1 channels mediate a depolarization of hippocampal astrocytes under hyperammonemic conditions <i>in situ<\/i>"],"prefix":"10.1002","volume":"60","author":[{"given":"Jonathan","family":"Stephan","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicole","family":"Haack","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karl W.","family":"Kafitz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simone","family":"Durry","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Koch","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Hochstrate","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gerald","family":"Seifert","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"Steinh\u00e4user","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christine R.","family":"Rose","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2012,3,19]]},"reference":[{"key":"e_1_2_6_2_1","first-page":"103","volume-title":"Encyclopedia of measurement and statistics","author":"Abdi H","year":"2007"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2010.07.024"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.1983.49.6.1381"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(97)01288-2"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/1098-1136(200010)32:1<1::AID-GLIA10>3.0.CO;2-W"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(99)01674-1"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.1978.tb07044.x"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11011-008-9112-7"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/327707a0"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1582-4934.2006.tb00289.x"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2010.03.012"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0197-0186(00)00026-7"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2078-10.2010"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.18-12-04425.1998"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0301-0082(00)00067-8"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0723-07.2007"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/bip.21034"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0301-0082(02)00019-9"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.510310322"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M405985200"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.2001.281.3.C922"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.61.6.669"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11011-010-9180-3"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneumeth.2007.11.022"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-005-1483-6"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.20817"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2010.07009.x"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(79)90470-0"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.20-15-05733.2000"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2004.06.008"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.20455"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2009.182279"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.20624"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.20027"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0301-0082(00)00043-5"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1460-9568.1999.00418.x"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneumeth.2006.01.009"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.2001.86.2.836"},{"issue":"4","key":"e_1_2_6_40_1","doi-asserted-by":"crossref","first-page":"C883","DOI":"10.1152\/ajpcell.1998.274.4.C883","article-title":"Intracellular acidification induced by passive and active transport of ammonium ions in astrocytes","volume":"274","author":"Nagaraja TN","year":"1998","journal-title":"Am J Physiol"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth706"},{"key":"e_1_2_6_42_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2008.05615.x"},{"key":"e_1_2_6_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.jcbfm.9600480"},{"key":"e_1_2_6_44_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.1973.36.5.855"},{"key":"e_1_2_6_45_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.1981.61.2.296"},{"key":"e_1_2_6_46_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M412448200"},{"key":"e_1_2_6_47_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1432-1327.2000.01671.x"},{"key":"e_1_2_6_48_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3790-08.2009"},{"key":"e_1_2_6_49_1","doi-asserted-by":"publisher","DOI":"10.1177\/1073858402008003011"},{"key":"e_1_2_6_50_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.1992.tb00897.x"},{"key":"e_1_2_6_51_1","doi-asserted-by":"publisher","DOI":"10.1097\/00004647-199701000-00006"},{"key":"e_1_2_6_52_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1984.sp015397"},{"key":"e_1_2_6_53_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2005.04583.x"},{"key":"e_1_2_6_54_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0037-06.2006"},{"key":"e_1_2_6_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0197-0186(99)00137-0"},{"key":"e_1_2_6_56_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.1999.00921.x"},{"key":"e_1_2_6_57_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00570.2005"}],"container-title":["Glia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fglia.22328","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/glia.22328","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,14]],"date-time":"2023-10-14T14:31:25Z","timestamp":1697293885000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/glia.22328"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,3,19]]},"references-count":56,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2012,5]]}},"alternative-id":["10.1002\/glia.22328"],"URL":"https:\/\/doi.org\/10.1002\/glia.22328","archive":["Portico"],"relation":{},"ISSN":["0894-1491","1098-1136"],"issn-type":[{"value":"0894-1491","type":"print"},{"value":"1098-1136","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,3,19]]}}}