{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T07:08:31Z","timestamp":1790233711498,"version":"4.1.0"},"reference-count":29,"publisher":"American Physiological Society","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Neurophysiology"],"published-print":{"date-parts":[[2000,8,1]]},"abstract":"<jats:p>Calcium chelators have been widely used in electrophysiological recordings of N-methyl-d-aspartate (NMDA) receptor\u2013mediated currents, as well as in studies of excitotoxicity. Intracellularly applied calcium chelators are known to inhibit, at least in part, such calcium-dependent processes as calmodulin-dependent inactivation, calcineurin-dependent desensitization, and rundown of NMDA receptors. On the other hand, the functional consequences and potential nonspecific effects of extracellularly applied chelators have not been extensively investigated. In whole-cell patch-clamp recordings from human embryonic kidney (HEK) 293 cells transiently transfected with recombinant NMDA receptors, we found that addition of calcium chelators such as EGTA shifted the glutamate dose-response curve to the right, from an EC<jats:sub>50<\/jats:sub>for NR1A\/NR2A of 8 \u03bcM in 1.8 mM Ca<jats:sup>2+<\/jats:sup>to \u223c24 \u03bcM in a solution containing nominal 0 Ca<jats:sup>2+<\/jats:sup>\/5 mM EGTA and further to \u223c80 \u03bcM in 20 mM EGTA. A similar shift in glutamate dose-response was observed for NR1A\/NR2B currents. This dose-response shift was not due to a decrease in extracellular Ca<jats:sup>2+<\/jats:sup>concentration because there was no change in the glutamate EC<jats:sub>50<\/jats:sub>at Ca<jats:sup>2+<\/jats:sup>concentrations ranging from 10 mM to nominal 0\/200 \u03bcM EGTA. Moreover, addition of 5 mM EGTA fully chelated with 6.8 mM Ca<jats:sup>2+<\/jats:sup>did not produce any shift in the glutamate dose-response curve. We propose that calcium chelators, containing four free carboxyl moieties, competitively inhibit glutamate binding to NMDA receptors.<\/jats:p>","DOI":"10.1152\/jn.2000.84.2.693","type":"journal-article","created":{"date-parts":[[2017,12,21]],"date-time":"2017-12-21T13:22:37Z","timestamp":1513862557000},"page":"693-697","source":"Crossref","is-referenced-by-count":14,"title":["Competitive Inhibition of NMDA Receptor\u2013Mediated Currents by Extracellular Calcium Chelators"],"prefix":"10.1152","volume":"84","author":[{"given":"Nansheng","family":"Chen","sequence":"first","affiliation":[{"name":"Kinsmen Laboratory of Neurological Research, Department of Psychiatry,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy H.","family":"Murphy","sequence":"additional","affiliation":[{"name":"Kinsmen Laboratory of Neurological Research, Department of Psychiatry,"},{"name":"Department of Physiology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lynn A.","family":"Raymond","sequence":"additional","affiliation":[{"name":"Kinsmen Laboratory of Neurological Research, Department of Psychiatry,"},{"name":"Department of Physiology, and"},{"name":"Department of Medicine, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1988.sp017078"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.7.8.2745"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1124\/mol.51.6.1015"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.19-16-06844.1999"},{"key":"B5","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/S0031-6997(24)01394-2","volume":"51","author":"Dingledine R","year":"1999","journal-title":"Pharmacol Rev"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81052-1"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1126\/science.7716515"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1992.sp019331"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.14-07-04561.1994"},{"key":"B10","first-page":"237","volume":"27","author":"Heinemann U","year":"1977","journal-title":"Exp Brain Res"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.33.20805"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(93)90209-A"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1007\/BF00373905"},{"key":"B14","doi-asserted-by":"crossref","first-page":"1680","DOI":"10.1016\/S0026-895X(25)09630-0","volume":"50","author":"Krupp JJ","year":"1996","journal-title":"Mol Pharmacol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.19-04-01165.1999"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.13-02-00674.1993"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199403033300907"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.1994.74.3.723"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(88)90941-9"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.17-15-05711.1997"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1006\/mcne.1996.0008"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(93)90197-Y"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1993.sp019884"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3940(96)12924-4"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1098\/rspb.1996.0159"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1038\/385439a0"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.13.7012"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.19-21-j0003.1999"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)80553-X"}],"container-title":["Journal of Neurophysiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.physiology.org\/doi\/pdf\/10.1152\/jn.2000.84.2.693","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,29]],"date-time":"2025-06-29T03:36:32Z","timestamp":1751168192000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/jn.2000.84.2.693"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2000,8,1]]},"references-count":29,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2000,8,1]]}},"alternative-id":["10.1152\/jn.2000.84.2.693"],"URL":"https:\/\/doi.org\/10.1152\/jn.2000.84.2.693","relation":{},"ISSN":["0022-3077","1522-1598"],"issn-type":[{"value":"0022-3077","type":"print"},{"value":"1522-1598","type":"electronic"}],"subject":[],"published":{"date-parts":[[2000,8,1]]}}}