{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T00:41:39Z","timestamp":1791160899605,"version":"4.1.0"},"reference-count":42,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2006,1,18]],"date-time":"2006-01-18T00:00:00Z","timestamp":1137542400000},"content-version":"vor","delay-in-days":17,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Eur J of Neuroscience"],"published-print":{"date-parts":[[2006,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The Cl<jats:sup>\u2013<\/jats:sup>\u2010extruding neuron\u2010specific K<jats:sup>+<\/jats:sup>\u2013Cl<jats:sup>\u2013<\/jats:sup> cotransporter KCC2, which establishes hyperpolarizing inhibition, can transport NH<jats:sub>4<\/jats:sub><jats:sup>+<\/jats:sup> instead of K<jats:sup>+<\/jats:sup>. It is, however, not clear whether KCC2 provides the only pathway for neuronal NH<jats:sub>4<\/jats:sub><jats:sup>+<\/jats:sup> uptake. We therefore investigated NH<jats:sub>4<\/jats:sub><jats:sup>+<\/jats:sup> uptake in cultured rat brain neurons. In neurons cultured for &gt;\u200a4\u2003weeks, the response to NH<jats:sub>4<\/jats:sub>Cl applications (5\u2003m<jats:sc>m<\/jats:sc>) consisted of an alkaline shift which reversed to an acid shift within seconds. Rebound acid shifts which followed brief applications of NH<jats:sub>4<\/jats:sub>Cl were blocked by furosemide (100\u2003\u00b5<jats:sc>m<\/jats:sc>). They were rather insensitive to bumetanide (1 and 100\u2003\u00b5<jats:sc>m<\/jats:sc>), in contrast to those induced in cultured glial cells. Rebound acid shifts persisted in the presence of 1\u2003m<jats:sc>m<\/jats:sc> Ba<jats:sup>2+<\/jats:sup> and in Na<jats:sup>+<\/jats:sup>\u2010free solution but were inhibited by extracellular K<jats:sup>+<\/jats:sup>. In neurons with depolarizing GABA responses, indicating the absence of functional KCC2, applications of NH<jats:sub>4<\/jats:sub>Cl barely induced an acidosis. However, large rebound acid shifts occurred in neurons that had changed their GABA response from Ca<jats:sup>2+<\/jats:sup> increases to Ca<jats:sup>2+<\/jats:sup> decreases. Rebound acid shifts continued to increase even after the change in the GABA response had occurred and could be induced earlier in neurons transfected with KCC2 cDNA. We conclude that KCC2 provides the main pathway for fast neuronal NH<jats:sub>4<\/jats:sub><jats:sup>+<\/jats:sup> uptake. Therefore, NH<jats:sub>4<\/jats:sub>Cl\u2010induced rebound acid shifts can be used to indicate the development of KCC2 function. Further, the well known up\u2010regulation of KCC2 function during development has the inevitable consequence of opening a major pathway for NH<jats:sub>4<\/jats:sub><jats:sup>+<\/jats:sup> influx, which can be relevant under pathophysiological conditions.<\/jats:p>","DOI":"10.1111\/j.1460-9568.2005.04583.x","type":"journal-article","created":{"date-parts":[[2006,1,18]],"date-time":"2006-01-18T20:37:05Z","timestamp":1137616625000},"page":"454-464","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Intracellular acidification in neurons induced by ammonium depends on KCC2 function"],"prefix":"10.1111","volume":"23","author":[{"given":"Stefan","family":"Titz","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheriar","family":"Hormuzdi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Lewen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah","family":"Monyer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrich","family":"Misgeld","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2006,1,18]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1982.sp014305"},{"key":"e_1_2_7_3_1","doi-asserted-by":"crossref","first-page":"C1607","DOI":"10.1152\/ajpcell.1994.267.6.C1607","article-title":"Cl\u2013\u2010dependent NH4\n                  + transport mechanisms in medullary thick ascending limb cells","volume":"267","author":"Amlal H.","year":"1994","journal-title":"Am. 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