{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T19:32:27Z","timestamp":1771356747458,"version":"3.50.1"},"reference-count":60,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2004,2,23]],"date-time":"2004-02-23T00:00:00Z","timestamp":1077494400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2004,3]]},"abstract":"The effects of changing cytosolic [Mg2+<\/jats:sup>] ([Mg2+<\/jats:sup>]i<\/jats:sub>)<\/jats:styled-content> on l<\/jats:sc>\u2010type Ca2+<\/jats:sup> currents were investigated in rat cardiac ventricular myocytes voltage\u2010clamped with patch pipettes containing salt solutions with defined [Mg2+<\/jats:sup>] and [Ca2+<\/jats:sup>]. To control [Mg2+<\/jats:sup>]i<\/jats:sub> and cytosolic [Ca2+<\/jats:sup>] ([Ca2+<\/jats:sup>]i<\/jats:sub>), the pipette solution included 30 mm<\/jats:sc> citrate and 10 mm<\/jats:sc> ATP along with 5 mm<\/jats:sc> EGTA (slow Ca2+<\/jats:sup> buffer) or 15 mm<\/jats:sc> EGTA plus 5 mm<\/jats:sc> BAPTA (fast Ca2+<\/jats:sup> buffer). With pipette [Ca2+<\/jats:sup>] ([Ca2+<\/jats:sup>]p<\/jats:sub>) set at 100 nm<\/jats:sc> using a slow Ca2+<\/jats:sup> buffer and pipette [Mg2+<\/jats:sup>] ([Mg2+<\/jats:sup>]p<\/jats:sub>) set at 0.2 mm<\/jats:sc>, peak l<\/jats:sc>\u2010type Ca2+<\/jats:sup> current density (I<\/jats:italic>Ca<\/jats:sub>) was 17.0 \u00b1 2.2 pA pF\u22121<\/jats:sup>. Under the same conditions, but with [Mg2+<\/jats:sup>]p<\/jats:sub> set to 1.8 mm<\/jats:sc>, I<\/jats:italic>Ca<\/jats:sub> was 5.6 \u00b1 1.0 pA pF\u22121<\/jats:sup>, a 64 \u00b1 2.8% decrease in amplitude. This decrease in I<\/jats:italic>Ca<\/jats:sub> was accompanied by an acceleration and a \u20138 mV shift in the voltage dependence of current inactivation. The [Mg2+<\/jats:sup>]p<\/jats:sub>\u2010dependent decrease in I<\/jats:italic>Ca<\/jats:sub> was not significantly different when myocytes were preincubated with 10 \u03bcm<\/jats:sc> forskolin and 300 \u03bcm<\/jats:sc> 3\u2010isobutyl\u20101\u2010methylxanthine and voltage\u2010clamped with pipettes containing 50 \u03bcm<\/jats:sc> okadaic acid, to maximize Ca2+<\/jats:sup> channel phosphorylation. However, when myocytes were voltage\u2010clamped with pipettes containing protein phosphatase 2A, to promote channel dephosphorylation, I<\/jats:italic>Ca<\/jats:sub> decreased only 25 \u00b1 3.4% on changing [Mg2+<\/jats:sup>]p<\/jats:sub> from 0.2 to 1.8 mm<\/jats:sc>. In the presence of 0.2 mm<\/jats:sc>[Mg2+<\/jats:sup>]p<\/jats:sub>, changing channel phosphorylation conditions altered I<\/jats:italic>Ca<\/jats:sub> over a 4\u2010fold range; however, with 1.8 mm<\/jats:sc>[Mg2+<\/jats:sup>]p<\/jats:sub><\/jats:styled-content>, these same manoeuvres had a much smaller effect on I<\/jats:italic>Ca<\/jats:sub>. These data suggest that [Mg2+<\/jats:sup>]i<\/jats:sub> can antagonize the effects of phosphorylation on channel gating kinetics. Setting [Ca2+<\/jats:sup>]p<\/jats:sub> to 1, 100 or 300 nm<\/jats:sc> also showed that the [Mg2+<\/jats:sup>]p<\/jats:sub>\u2010induced reduction of I<\/jats:italic>Ca<\/jats:sub> was smaller at the lowest [Ca2+<\/jats:sup>]p<\/jats:sub>, irrespective of channel phosphorylation conditions. This interaction between [Ca2+<\/jats:sup>]i<\/jats:sub> and [Mg2+<\/jats:sup>]i<\/jats:sub> to modulate I<\/jats:italic>Ca<\/jats:sub> was not significantly affected by ryanodine, fast Ca2+<\/jats:sup> buffers or inhibitors of calmodulin, calmodulin\u2010dependent kinase and calcineurin. Thus, physiologically relevant [Mg2+<\/jats:sup>]i<\/jats:sub> modulates I<\/jats:italic>Ca<\/jats:sub> by counteracting the effects of Ca2+<\/jats:sup> channel phosphorylation and by an unknown [Ca2+<\/jats:sup>]i<\/jats:sub>\u2010dependent mechanism. The magnitude of these effects suggests that changes in [Mg2+<\/jats:sup>]i<\/jats:sub> could be critical in regulating l<\/jats:sc>\u2010type channel gating.<\/jats:p>","DOI":"10.1113\/jphysiol.2003.048538","type":"journal-article","created":{"date-parts":[[2003,11,18]],"date-time":"2003-11-18T01:23:14Z","timestamp":1069118594000},"page":"383-396","source":"Crossref","is-referenced-by-count":44,"title":["Regulation of L\u2010type calcium current by intracellular magnesium in rat cardiac myocytes"],"prefix":"10.1113","volume":"555","author":[{"given":"Min","family":"Wang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michiko","family":"Tashiro","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joshua 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