{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T07:37:27Z","timestamp":1773301047297,"version":"3.50.1"},"reference-count":44,"publisher":"American Physiological Society","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Cell Physiology"],"published-print":{"date-parts":[[1998,4,1]]},"abstract":"<jats:p> We describe an unconventional response of intracellular pH to NH<jats:sub>4<\/jats:sub>Cl in mouse cerebral astrocytes. Rapid alkalinization reversed abruptly to be replaced by an intense sustained acidification in the continued presence of NH<jats:sub>4<\/jats:sub>Cl. We hypothesize that high-velocity [Formula: see text] influx persisted after the distribution of ammonia attained steady state. From the initial rate of acidification elicited by 1 mM NH<jats:sub>4<\/jats:sub>Cl in bicarbonate-buffered solution, we estimate that [Formula: see text] entered at a velocity of at least 31.5 nmol \u22c5 min<jats:sup>\u22121<\/jats:sup> \u22c5 mg protein<jats:sup>\u22121<\/jats:sup>. This rate increased with NH<jats:sub>4<\/jats:sub>Cl concentration, not saturating at up to 20 mM NH<jats:sub>4<\/jats:sub>Cl. Acidification was attenuated by raising or lowering extracellular K<jats:sup>+<\/jats:sup> concentration. Ba<jats:sup>2+<\/jats:sup> (50 \u03bcM) inhibited the acidification rate by 80.6%, suggesting inwardly rectifying K<jats:sup>+<\/jats:sup> channels as the primary[Formula: see text] entry pathway. Acidification was 10-fold slower in rat hippocampal astrocytes, consistent with the difference reported for K<jats:sup>+<\/jats:sup> flux in vitro. The combination of Ba<jats:sup>2+<\/jats:sup> and bumetanide prevented net acidification by 1 mM NH<jats:sub>4<\/jats:sub>Cl, identifying the Na<jats:sup>+<\/jats:sup>-K<jats:sup>+<\/jats:sup>-2Cl<jats:sup>\u2212<\/jats:sup>cotransporter as a second [Formula: see text] entry route.[Formula: see text] entry via K<jats:sup>+<\/jats:sup> transport pathways could impact \u201cbuffering\u201d of ammonia by astrocytes and could initiate the elevation of extracellular K<jats:sup>+<\/jats:sup>concentration and astrocyte swelling observed in acute hyperammonemia. <\/jats:p>","DOI":"10.1152\/ajpcell.1998.274.4.c883","type":"journal-article","created":{"date-parts":[[2017,12,24]],"date-time":"2017-12-24T17:29:43Z","timestamp":1514136583000},"page":"C883-C891","source":"Crossref","is-referenced-by-count":148,"title":["Intracellular acidification induced by passive  and active transport of ammonium ions in astrocytes"],"prefix":"10.1152","volume":"274","author":[{"given":"Tavarekere N.","family":"Nagaraja","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Experimental Therapeutics, University of Maryland School of Medicine, Baltimore, Maryland 21202"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Neville","family":"Brookes","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Experimental Therapeutics, University of Maryland School of Medicine, Baltimore, Maryland 21202"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(17)31742-8"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.ne.13.030190.002301"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.67.1.91"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1152\/ajplegacy.1976.231.3.799"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1996.271.4.C1146"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1996.271.4.C1131"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1002\/glia.440080404"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-1136(199709)21:1<64::AID-GLIA7>3.0.CO;2-1"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(93)9002-7"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1994.267.6.C1633"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(89)90320-5"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/0301-0082(90)90034-E"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/0166-2236(96)10042-4"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.1987.67.2.440"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(95)00588-Z"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.1988.255.1.F57"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.ph.56.030194.003203"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1007\/BF01869680"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.ph.51.030189.002303"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.1996.66010169.x"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.1997.68031209.x"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1994.sp020048"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.99.3.435"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(85)91282-X"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1139\/y92-275"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.ne.07.030184.001353"},{"key":"B28","first-page":"1497","volume":"22","author":"Nagaraja T. 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