{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,9,25]],"date-time":"2023-09-25T08:51:05Z","timestamp":1695631865324},"reference-count":12,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2006,1,24]],"date-time":"2006-01-24T00:00:00Z","timestamp":1138060800000},"content-version":"vor","delay-in-days":1180,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of the New York Academy of Sciences"],"published-print":{"date-parts":[[2002,11]]},"abstract":"<jats:p><jats:bold>A<jats:sc>bstract<\/jats:sc>: <\/jats:bold> Intracellular Na<jats:sup>+<\/jats:sup> and H<jats:sup>+<\/jats:sup> synergistically inhibit the squid Na<jats:sup>+<\/jats:sup>\/Ca<jats:sup>2+<\/jats:sup> exchanger by reducing the affinity for Ca<jats:sup>2+<\/jats:sup> of its regulatory site. MgATP antagonizes H<jats:sup>+<\/jats:sup><jats:sub>i<\/jats:sub> and Na<jats:sup>+<\/jats:sup><jats:sub>i<\/jats:sub> inhibition; this effect must occur through a phosphorylation\u2010dephosphorylation process, because exogenous protein phosphatases prevent MgATP activation of the exchanger. Protection by ATP against H<jats:sup>+<\/jats:sup><jats:sub>i<\/jats:sub> and Na<jats:sup>+<\/jats:sup><jats:sub>i<\/jats:sub> inhibition happens by decreasing the apparent affinity for the synergistic binding of these cations to the carrier. In this way ATP modifies the apparent affinity for Ca<jats:sup>2+<\/jats:sup> of its regulatory site. Mg<jats:sup>2+<\/jats:sup> ions play an important role in the process because they are essential for ATP activation of Na<jats:sup>+<\/jats:sup>\/Ca<jats:sup>2+<\/jats:sup> exchange but can also promote deactivation of the ATP upregulated exchanger. At constant [ATP], activation at low [Mg<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub> is followed by deactivation as [Mg<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub> is increased. The most likely explanation for deactivation is stimulation of endogenous phosphatases. We developed a kinetic model that predicts all H<jats:sup>+<\/jats:sup><jats:sub>i<\/jats:sub>, Na<jats:sup>+<\/jats:sup><jats:sub>i<\/jats:sub>, and MgATP described above. This scheme includes the following conditions: (i) The binding of Ca<jats:sup>2+<\/jats:sup> to the regulatory site is essential for the binding of Na<jats:sup>+<\/jats:sup><jats:sub>i<\/jats:sub> or Ca<jats:sup>2+<\/jats:sup><jats:sub>i<\/jats:sub> to the transporting sites. (ii) The binding of a first H<jats:sup>+<\/jats:sup><jats:sub>i<\/jats:sub> to the carrier displaces Ca<jats:sup>2+<\/jats:sup><jats:sub>i<\/jats:sub> from its regulatory site and allows binding of one Na<jats:sup>+<\/jats:sup> forming a H.E<jats:sub>1<\/jats:sub>.Na complex. The H.E<jats:sub>1<\/jats:sub>.Na complex can bind a second H<jats:sup>+<\/jats:sup><jats:sub>i<\/jats:sub> forming a dead\u2010end inhibitory H<jats:sub>2<\/jats:sub>.E<jats:sub>1<\/jats:sub>.Na complex. (iii) MgATP, through an unspecified phosphorylation process, decreases the apparent affinity for the synergistic H<jats:sup>+<\/jats:sup><jats:sub>i<\/jats:sub> and Na<jats:sup>+<\/jats:sup><jats:sub>i<\/jats:sub> binding to the carrier.<\/jats:p>","DOI":"10.1111\/j.1749-6632.2002.tb04745.x","type":"journal-article","created":{"date-parts":[[2010,7,20]],"date-time":"2010-07-20T22:48:05Z","timestamp":1279666085000},"page":"224-236","source":"Crossref","is-referenced-by-count":2,"title":["Intracellular Ionic and Metabolic Regulation of Squid Nerve Na<sup>+<\/sup>\/Ca<sup>2+<\/sup> Exchanger"],"prefix":"10.1111","volume":"976","author":[{"given":"REINALDO","family":"DIPOLO","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"LUIS","family":"BEAUG\u00c9","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2006,1,24]]},"reference":[{"key":"e_1_2_5_2_2","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1152\/physrev.1999.79.3.763","article-title":"Sodium\/calcium exchange: its physiological implications","volume":"79","author":"Blaustein M.P.","year":"1999","journal-title":"Physiol. Rev."},{"key":"e_1_2_5_3_2","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.72.4.443"},{"key":"e_1_2_5_4_2","first-page":"933","article-title":"Steady\u2010state and dynamic properties of cardiac sodium\u2010calcium exchanger","volume":"100","author":"Hilgemann D.W.","year":"1992","journal-title":"Secondary modulation by cytoplasm calcium and ATP. J. Gen. 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Physiol."},{"key":"e_1_2_5_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(96)01416-0"},{"key":"e_1_2_5_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/0005-2736(87)90432-9"},{"key":"e_1_2_5_13_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2001.013377"}],"container-title":["Annals of the New York Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fj.1749-6632.2002.tb04745.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/nyaspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/j.1749-6632.2002.tb04745.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,25]],"date-time":"2023-09-25T08:19:18Z","timestamp":1695629958000},"score":1,"resource":{"primary":{"URL":"https:\/\/nyaspubs.onlinelibrary.wiley.com\/doi\/10.1111\/j.1749-6632.2002.tb04745.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2002,11]]},"references-count":12,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2002,11]]}},"alternative-id":["10.1111\/j.1749-6632.2002.tb04745.x"],"URL":"https:\/\/doi.org\/10.1111\/j.1749-6632.2002.tb04745.x","archive":["Portico"],"relation":{},"ISSN":["0077-8923","1749-6632"],"issn-type":[{"value":"0077-8923","type":"print"},{"value":"1749-6632","type":"electronic"}],"subject":[],"published":{"date-parts":[[2002,11]]}}}