TY - JOUR T1 - 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 JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 1104 LP - 1110 VL - 292 IS - 3 AU - Yingying Li-Smerin AU - Elias Aizenman AU - Jon W. Johnson Y1 - 2000/03/01 UR - http://jpet.aspetjournals.org/content/292/3/1104.abstract N2 - 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 ER -