Biomaterial Database

The inhibition of single N-methyl-D-aspartate-activated channels by zinc ions on cultured rat neurones. 1990

P Legendre, and G L Westbrook

Vollum Institute, Oregon Health Sciences University, Portland 97201.

1. Single channels activated by N-methyl-D-aspartate (NMDA) were studied in outside-out patches of cultured hippocampal neurones in the presence of glycine and absence of magnesium. The effects of the transition metal ions zinc and cadmium on NMDA channels were tested by placing the membrane patch at the mouth of one of an array of large barrelled flow pipes. 2. Amplitude histograms revealed several conductance levels between 5 and 45 pS with the majority of NMDA-activated openings greater than 25 pS. Zinc (5-100 microM) and cadmium (30-100 microM) reduced the number of large conductance events in a voltage-independent manner. Zinc (30 microM) reduced the large conductance openings by approximately 70-80%. The small number of events under 20 pS precluded quantitative assessment of the effects of zinc and cadmium on these conductance levels. Zinc inhibition of the calculated macroscopic current due to NMDA-activated channels could be fitted with a single binding site isotherm with an IC50 of 12 microM. 3. Zinc and cadmium also reduced the mean open time of the two largest conductance events of 38 and 43 pS; this reduction was voltage independent. Open-time histograms were fitted with the sum of two exponentials. In the presence of 5 microM-NMDA at -60 mV, tau o2 = 10.49 ms and tau o1 = 1.47 ms; in 30 microM-zinc, tau o2 = 3.49 and tau o1 = 0.8 ms. The 'blocking' rate constant calculated at a membrane potential of +40 mV from the slope of 1/tau o2 vs. [zinc]o was 4 x 10(6) M-1 S-1. 4. Closed-time analysis revealed brief (tau c = 0.4-1.0 ms) zinc-insensitive gaps; longer closed-time intervals were not analysed since all patches contained more than one channel. Both burst duration and the number of bursts were reduced in the presence of zinc. 5. At holding potentials negative to -40 mV in magnesium-free solutions, zinc also induced high-frequency flickering of the open channel which included complete channel closures at 4 kHz filtering. No zinc-induced flickering was seen at positive membrane potentials. The flickering was dose dependent, becoming prominent at zinc concentrations above 30 microM. Cadmium did not induce flickering at concentrations up to 100 microM.(ABSTRACT TRUNCATED AT 400 WORDS)

UI	MeSH Term	Description	Entries
D007473	Ion Channels	Gated, ion-selective glycoproteins that traverse membranes. The stimulus for ION CHANNEL GATING can be due to a variety of stimuli such as LIGANDS, a TRANSMEMBRANE POTENTIAL DIFFERENCE, mechanical deformation or through INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS.	Membrane Channels,Ion Channel,Ionic Channel,Ionic Channels,Membrane Channel,Channel, Ion,Channel, Ionic,Channel, Membrane,Channels, Ion,Channels, Ionic,Channels, Membrane
D011919	Rats, Inbred Strains	Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding.	August Rats,Inbred Rat Strains,Inbred Strain of Rat,Inbred Strain of Rats,Inbred Strains of Rats,Rat, Inbred Strain,August Rat,Inbred Rat Strain,Inbred Strain Rat,Inbred Strain Rats,Inbred Strains Rat,Inbred Strains Rats,Rat Inbred Strain,Rat Inbred Strains,Rat Strain, Inbred,Rat Strains, Inbred,Rat, August,Rat, Inbred Strains,Rats Inbred Strain,Rats Inbred Strains,Rats, August,Rats, Inbred Strain,Strain Rat, Inbred,Strain Rats, Inbred,Strain, Inbred Rat,Strains, Inbred Rat
D002104	Cadmium	An element with atomic symbol Cd, atomic number 48, and atomic weight 112.41. It is a metal and ingestion will lead to CADMIUM POISONING.
D002478	Cells, Cultured	Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.	Cultured Cells,Cell, Cultured,Cultured Cell
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
D006624	Hippocampus	A curved elevation of GRAY MATTER extending the entire length of the floor of the TEMPORAL HORN of the LATERAL VENTRICLE (see also TEMPORAL LOBE). The hippocampus proper, subiculum, and DENTATE GYRUS constitute the hippocampal formation. Sometimes authors include the ENTORHINAL CORTEX in the hippocampal formation.	Ammon Horn,Cornu Ammonis,Hippocampal Formation,Subiculum,Ammon's Horn,Hippocampus Proper,Ammons Horn,Formation, Hippocampal,Formations, Hippocampal,Hippocampal Formations,Hippocampus Propers,Horn, Ammon,Horn, Ammon's,Proper, Hippocampus,Propers, Hippocampus,Subiculums
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
D001665	Binding Sites	The parts of a macromolecule that directly participate in its specific combination with another molecule.	Combining Site,Binding Site,Combining Sites,Site, Binding,Site, Combining,Sites, Binding,Sites, Combining
D001693	Biological Transport, Active	The movement of materials across cell membranes and epithelial layers against an electrochemical gradient, requiring the expenditure of metabolic energy.	Active Transport,Uphill Transport,Active Biological Transport,Biologic Transport, Active,Transport, Active Biological,Active Biologic Transport,Transport, Active,Transport, Active Biologic,Transport, Uphill
D013997	Time Factors	Elements of limited time intervals, contributing to particular results or situations.	Time Series,Factor, Time,Time Factor