Subunit-specific Redox Modulation of NMDA Receptors Expressed in Xenopus Oocytes

We have examined the effects of oxidizing and reducing agents on a number of subtypes of N-methyl-D-aspartate (NMDA) receptors expressed in Xenopus oocytes. Oocytes were injected with cRNA for the zeta 1 subunit from mouse to express homomeric receptors or with zeta 1 in combination with either epsilon 1, epsilon 2, epsilon 3 or epsilon 4 subunits to express heteromeric receptors. All heteromeric combinations resulted in receptors that were affected by the redox reagents, dithiothreitol (DTT) and 5-5-dithio-bis-2-nitrobenzoic acid (DTNB). However, the effects on the small currents from homomeric receptors were quite variable. The zeta 1/epsilon 3 combination showed a greater enhancement by DTT than any of the other combinations. All four receptors expressed showed both a component of persistent potentiation and a slowly reversible component. The reversible component was largest for zeta 1/epsilon 3. Additional experiments were done with S-nitrosocysteine (SNOC), a nitric oxide donor that may affect NMDA receptors by oxidation. SNOC had transient effects on the four heteromeric subunit combinations. The different sensitivities of particular subunit combinations may have pharmacological and clinical significance.