Biomaterial Database

Separating dual effects of zinc at recombinant N-methyl-D-aspartate receptors. 1996

K Williams

Department of Pharmacology, University of Pennsylvania, School of Medicine, Philadelphia 19104-6084, USA.

The effects of Zn2+ on recombinant N-methyl-D-aspartate (NMDA) receptors expressed in Xenopus oocytes were examined. Zn2+ inhibited macroscopic currents induced by NMDA at both NR1/NR2B and NR1/NR2A receptors. At NR1/NR2B receptors the Zn2+ concentration-inhibition curve was monophasic, with an apparent affinity for Zn2/ of 1.6 microM, and inhibition by Zn2+ was not voltage-dependent. In contrast, the Zn2+ concentration-inhibition curve at NR1/NR2A receptors was biphasic, with high (Ki = 0.08 microM) and low (Ki = 30 microM) affinity components. The high affinity component produced a maximal inhibition of 45% of macroscopic NMDA currents and was not voltage-dependent. Thus, Zn2+ is more potent in producing voltage-independent block at NR1/NR2A than at NR1/NR2B receptors, but the maximal effect of Zn2+ is smaller at NR1/NR2A than at NR1/NR2B receptors. The low affinity component of Zn2+ inhibition at NR1/NR2A receptors was voltage-dependent and may represent an open-channel blocking effect of Zn2+. Differential effects of Zn2+ at recombinant NMDA receptors containing different NR2 subunits provide a potential marker for distinguishing subtypes of native NMDA receptors and for dissecting the site and mechanism of action of Zn2+ at these receptors.

UI	MeSH Term	Description	Entries
D009865	Oocytes	Female germ cells derived from OOGONIA and termed OOCYTES when they enter MEIOSIS. The primary oocytes begin meiosis but are arrested at the diplotene state until OVULATION at PUBERTY to give rise to haploid secondary oocytes or ova (OVUM).	Ovocytes,Oocyte,Ovocyte
D004305	Dose-Response Relationship, Drug	The relationship between the dose of an administered drug and the response of the organism to the drug.	Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D014981	Xenopus	An aquatic genus of the family, Pipidae, occurring in Africa and distinguished by having black horny claws on three inner hind toes.
D015032	Zinc	A metallic element of atomic number 30 and atomic weight 65.38. It is a necessary trace element in the diet, forming an essential part of many enzymes, and playing an important role in protein synthesis and in cell division. Zinc deficiency is associated with ANEMIA, short stature, HYPOGONADISM, impaired WOUND HEALING, and geophagia. It is known by the symbol Zn.
D016194	Receptors, N-Methyl-D-Aspartate	A class of ionotropic glutamate receptors characterized by affinity for N-methyl-D-aspartate. NMDA receptors have an allosteric binding site for glycine which must be occupied for the channel to open efficiently and a site within the channel itself to which magnesium ions bind in a voltage-dependent manner. The positive voltage dependence of channel conductance and the high permeability of the conducting channel to calcium ions (as well as to monovalent cations) are important in excitotoxicity and neuronal plasticity.	N-Methyl-D-Aspartate Receptor,N-Methyl-D-Aspartate Receptors,NMDA Receptor,NMDA Receptor-Ionophore Complex,NMDA Receptors,Receptors, NMDA,N-Methylaspartate Receptors,Receptors, N-Methylaspartate,N Methyl D Aspartate Receptor,N Methyl D Aspartate Receptors,N Methylaspartate Receptors,NMDA Receptor Ionophore Complex,Receptor, N-Methyl-D-Aspartate,Receptor, NMDA,Receptors, N Methyl D Aspartate,Receptors, N Methylaspartate