PT - JOURNAL ARTICLE AU - Li-Smerin, Yingying AU - Aizenman, Elias AU - Johnson, Jon W. TI - Inhibition by Intracellular Mg<sup>2+</sup> of Recombinant<em>N</em>-Methyl-<span class="sc">d</span>-aspartate Receptors Expressed in Chinese Hamster Ovary Cells DP - 2000 Mar 01 TA - Journal of Pharmacology and Experimental Therapeutics PG - 1104--1110 VI - 292 IP - 3 4099 - http://jpet.aspetjournals.org/content/292/3/1104.short 4100 - http://jpet.aspetjournals.org/content/292/3/1104.full SO - J Pharmacol Exp Ther2000 Mar 01; 292 AB - Intracellular Mg2+ (Mgi2+) inhibits theN-methyl-d-aspartate (NMDA) subtype of glutamate receptors in cultured cortical neurons. To examine the effects of Mgi2+ on recombinant NMDA receptors composed of subunit combinations found in cortical neurons, we expressed heteromeric receptors composed of NR1/NR2A and of NR1/NR2B subunits in Chinese hamster ovary (CHO) cells. We recorded whole-cell currents from the recombinant receptors in the absence and presence of Mgi2+. The voltage dependence of control (0 Mgi2+) NMDA-activated currents obtained from CHO cells transfected with NR1/NR2A and with NR1/NR2B receptors showed outward rectification, a property that has been observed previously in native cortical NMDA receptors. The magnitude and voltage dependence of inhibition by Mgi2+ of NMDA-activated currents were similar in CHO cells transfected with NR1/NR2A receptors, CHO cells transfected with NR1/NR2B receptors, and in cultured neurons expressing native NMDA receptors. These observations suggest that Mgi2+ has uniform effects on the native NMDA receptors expressed in cortical neurons. Furthermore, inhibition by Mgi2+ must not depend on intracellular factors or post-translational receptor modifications that are specific to neurons. Finally, the results indicate that the previously observed differences between whole-cell and outside-out patch measurements of Mgi2+ inhibition could not result from poor control of voltage or Mgi2+ concentration in the dendrites of neurons. The most likely alternative explanation is that patch excision causes an alteration in NMDA receptors that results in more effective inhibition by Mgi2+. The American Society for Pharmacology and Experimental Therapeutics