Mg2+ ions reduce microglial and THP-1 cell neurotoxicity by inhibiting Ca2+ entry through purinergic channels. 
Mg(2+) is a known antagonist of some Ca(2+) ion channels.  It may therefore be able to counteract the toxic consequences of excessive Ca(2+) entry into immune-type cells.  Here we examined the effects of Mg(2+) on inflammation induced by Ca(2+) influx into microglia and THP-1 cells following activation of purinergic receptors.  Using tissue culture, an inflammatory response was induced by treatment with either the P2X7 purinergic receptor agonist 2',3'-[benzoyl-4-benzoyl]-ATP (BzATP) or the P2Y2,4 receptor agonist uridine 5'-triphosphate (UTP).  Both microglia and THP-1 cells expressed the mRNAs for these receptors.  Treatment produced a rapid rise in intracellular Ca(2+) which was significantly reduced by Mg(2+) or the calcium chelator BAPTA-AM.  Purinergic receptor stimulation activated the intracellular inflammatory pathway P38 MAP kinase and NFκB. This caused release of TNFα, IL-6, nitrite ions and other materials that are neurotoxic to SH-SY5Y cells.  These effects were all ameliorated by Mg(2+).  They were also partly ameliorated by the P2X7R antagonists, oxATP and KN-62, the P2YR antagonist MRS2179, and the store operated Ca(2+) channel blocker, SK96365.  These results indicate that elevated Mg(2+) is a broad spectrum inhibitor of Ca(2+) entry into microglia or THP-1 cells.  Mg(2+) administration may be a strategy for reducing the damaging consequences Ca(2+) induced neuroinflammation in degenerative neurological disorders such as Alzheimer disease and Parkinson disease.