{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T03:47:31Z","timestamp":1773287251798,"version":"3.50.1"},"reference-count":47,"publisher":"American Physiological Society","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Cell Physiology"],"published-print":{"date-parts":[[2006,7]]},"abstract":"<jats:p> Previous studies have shown that inhibition of L-type Ca<jats:sup>2+<\/jats:sup> current ( I<jats:sub>Ca<\/jats:sub>) by cytosolic free Mg<jats:sup>2+<\/jats:sup> concentration ([Mg<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>) is profoundly affected by activation of cAMP-dependent protein kinase pathways. To investigate the mechanism underlying this counterregulation of I<jats:sub>Ca<\/jats:sub>, rat cardiac myocytes and tsA201 cells expressing L-type Ca<jats:sup>2+<\/jats:sup> channels were whole cell voltage-clamped with patch pipettes in which [Mg<jats:sup>2+<\/jats:sup>] ([Mg<jats:sup>2+<\/jats:sup>]<jats:sub>p<\/jats:sub>) was buffered by citrate and ATP. In tsA201 cells expressing wild-type Ca<jats:sup>2+<\/jats:sup> channels (\u03b1<jats:sub>1C<\/jats:sub>\/\u03b2<jats:sub>2A<\/jats:sub>\/\u03b1<jats:sub>2<\/jats:sub>\u03b4), increasing [Mg<jats:sup>2+<\/jats:sup>]<jats:sub>p<\/jats:sub> from 0.2 mM to 1.8 mM decreased peak I<jats:sub>Ca<\/jats:sub> by 76 \u00b1 4.5% ( n = 7). Mg<jats:sup>2+<\/jats:sup>-dependent modulation of I<jats:sub>Ca<\/jats:sub> was also observed in cells loaded with ATP-\u03b3-S. With 0.2 mM [Mg<jats:sup>2+<\/jats:sup>]<jats:sub>p<\/jats:sub>, manipulating phosphorylation conditions by pipette application of protein kinase A (PKA) or phosphatase 2A (PP<jats:sub>2A<\/jats:sub>) produced large changes in I<jats:sub>Ca<\/jats:sub> amplitude; however, with 1.8 mM [Mg<jats:sup>2+<\/jats:sup>]<jats:sub>p<\/jats:sub>, these same manipulations had no significant effect on I<jats:sub>Ca<\/jats:sub>. With mutant channels lacking principal PKA phosphorylation sites (\u03b1<jats:sub>1C\/S1928A<\/jats:sub>\/\u03b2<jats:sub>2A\/S478A\/S479A<\/jats:sub>\/\u03b1<jats:sub>2<\/jats:sub>\u03b4), increasing [Mg<jats:sup>2+<\/jats:sup>]<jats:sub>p<\/jats:sub> had only small effects on I<jats:sub>Ca<\/jats:sub>. However, when channel open probability was increased by \u03b1<jats:sub>1C<\/jats:sub>-subunit truncation (\u03b1<jats:sub>1C\u03941905<\/jats:sub>\/\u03b2<jats:sub>2A\/S478A\/S479A<\/jats:sub>\/\u03b1<jats:sub>2<\/jats:sub>\u03b4), increasing [Mg<jats:sup>2+<\/jats:sup>]<jats:sub>p<\/jats:sub> greatly reduced peak I<jats:sub>Ca<\/jats:sub>. Correspondingly, in myocytes voltage-clamped with pipette PP<jats:sub>2A<\/jats:sub> to minimize channel phosphorylation, increasing [Mg<jats:sup>2+<\/jats:sup>]<jats:sub>p<\/jats:sub> produced a much larger reduction in I<jats:sub>Ca<\/jats:sub> when channel opening was promoted with BAY K8644. These data suggest that, around its physiological concentration range, cytosolic Mg<jats:sup>2+<\/jats:sup> modulates the extent to which channel phosphorylation regulates I<jats:sub>Ca<\/jats:sub>. This modulation does not necessarily involve changes in channel phosphorylation per se, but more generally appears to depend on the kinetics of gating induced by channel phosphorylation. <\/jats:p>","DOI":"10.1152\/ajpcell.00579.2005","type":"journal-article","created":{"date-parts":[[2006,2,16]],"date-time":"2006-02-16T01:25:23Z","timestamp":1140053123000},"page":"C83-C92","source":"Crossref","is-referenced-by-count":22,"title":["Channel phosphorylation and modulation of L-type Ca<sup>2+<\/sup> currents by cytosolic Mg<sup>2+<\/sup> concentration"],"prefix":"10.1152","volume":"291","author":[{"given":"Min","family":"Wang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joshua R.","family":"Berlin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"24","reference":[{"key":"R1","doi-asserted-by":"crossref","unstructured":"Agus ZS, Kelepouris E, Dukes I, and Morad M. 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