{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T05:24:34Z","timestamp":1792128274466,"version":"4.4.0"},"reference-count":51,"publisher":"Society for Neuroscience","issue":"11","license":[{"start":{"date-parts":[[2013,9,13]],"date-time":"2013-09-13T00:00:00Z","timestamp":1379030400000},"content-version":"vor","delay-in-days":184,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Neurosci."],"published-print":{"date-parts":[[2013,3,13]]},"abstract":"<jats:p>Gap junction (GJ) channels composed of Connexin36 (Cx36) are widely expressed in the mammalian CNS and form electrical synapses between neurons. Here we describe a novel modulatory mechanism of Cx36 GJ channels dependent on intracellular free magnesium ([Mg<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>). We examined junctional conductance (<jats:italic>g<\/jats:italic><jats:sub>j<\/jats:sub>) and its dependence on transjunctional voltage (<jats:italic>V<\/jats:italic><jats:sub>j<\/jats:sub>) at different [Mg<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>in cultures of HeLa or N2A cells expressing Cx36. We found that Cx36 GJs are partially inhibited at resting [Mg<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>. Thus,<jats:italic>g<\/jats:italic><jats:sub>j<\/jats:sub>can be augmented or reduced by lowering or increasing [Mg<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>, respectively. Similar changes in<jats:italic>g<\/jats:italic><jats:sub>j<\/jats:sub>and<jats:italic>V<\/jats:italic><jats:sub>j<\/jats:sub>-gating were observed using MgATP or K<jats:sub>2<\/jats:sub>ATP in pipette solutions, which increases or decreases [Mg<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>, respectively. Changes in phosphorylation of Cx36 or in intracellular free calcium concentration were not involved in the observed Mg<jats:sup>2+<\/jats:sup>-dependent modulation of<jats:italic>g<\/jats:italic><jats:sub>j<\/jats:sub>. Magnesium ions permeate the channel and transjunctional asymmetry in [Mg<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>resulted in asymmetric<jats:italic>V<\/jats:italic><jats:sub>j<\/jats:sub>-gating. The<jats:italic>g<\/jats:italic><jats:sub>j<\/jats:sub>of GJs formed of Cx26, Cx32, Cx43, Cx45, and Cx47 was also reduced by increasing [Mg<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>, but was not increased by lowering [Mg<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>; single-channel conductance did not change. We showed that [Mg<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>affects both open probability and the number of functional channels, likely through binding in the channel lumen. Finally, we showed that Cx36-containing electrical synapses between neurons of the trigeminal mesencephalic nucleus in rat brain slices are similarly affected by changes in [Mg<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>. Thus, this novel modulatory mechanism could underlie changes in neuronal synchronization under conditions in which ATP levels, and consequently [Mg<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>, are modified.<\/jats:p>","DOI":"10.1523\/jneurosci.2825-12.2013","type":"journal-article","created":{"date-parts":[[2013,3,13]],"date-time":"2013-03-13T16:54:54Z","timestamp":1363193694000},"page":"4741-4753","source":"Crossref","is-referenced-by-count":60,"title":["Intracellular Magnesium-Dependent Modulation of Gap Junction Channels Formed by Neuronal Connexin36"],"prefix":"10.1523","volume":"33","author":[{"given":"Nicol\u00e1s","family":"Palacios-Prado","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory","family":"Hoge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alina","family":"Marandykina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lina","family":"Rimkute","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandrine","family":"Chapuis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nerijus","family":"Paulauskas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vytenis A.","family":"Skeberdis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"O'Brien","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto E.","family":"Pereda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael V. 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