NDLI: NMDA receptors as targets of heavy metal interaction and toxicity

Content Provider	Springer Nature Link
Author	Marchetti, Carla Gavazzo, Paola
Copyright Year	2005
Abstract	TheN-methyl-D-aspartate (NMDA) receptor (NR) is a ligand-gated channel that carries the slow component of the glutamate-activated postsynaptic current. Divalent metal ions can affect the NR channel activity in a voltage-dependent (Mg$^{2+}$-like) or voltage-independent (Zn$^{2+}$-like) manner. We have studied the effect of two toxic metals, lead (Pb$^{2+}$) and nickel (Ni$^{2+}$) on recombinant NR1a-NR2A and NR1a-NR2B channels expressed in RNA-injectedXenopus laevis oocytes or in transiently transfected mammalian HEK293 cells. Pb$^{2+}$ caused a dose-dependent, but voltage-independent reversible inhibition of NMDA-activated channel activity similar for NR2A- and NR2B-containing receptors; it did not modify the single channel conductance, indicating that its binding site is located out of the ionic pathway of permeation. On the contrary, Ni$^{2+}$ had multiple and complex effects on NR channels. It determined a voltage-dependent, Mg$^{2+}$-like block by which the single channel amplitude and the mean open time were reduced in both NR2A- and NR2B-containing channels. While high (>100 µM) concentrations caused a dose-dependent reduction of the activity in both channel types, 30 µM determined a voltage-independent decrease in the frequency of NR1a-NR2A channel openings, but an increase in the frequency of NR1a-NR2B channel openings, confirming previous observations of a subunit-dependent effect of this metal. These results were interpreted under the hypothesis that Pb$^{2+}$mediates a Zn$^{2+}$-like voltage-independent allosteric modulation that, different from Zn$^{2+}$, is subunit-independent. In contrast, Ni$^{2+}$ has different modes of action, which are dependent on the NR2 subunit type present in the receptor and are likely to be related to different interaction sites. The NR2B-dependent facilitation bears close similarities with the polyamine-mediated potentiation.
Starting Page	245
Ending Page	258
Page Count	14
File Format	PDF
ISSN	10298428
Journal	Neurotoxicity Research
Volume Number	8
Issue Number	3-4
e-ISSN	14763524
Language	English
Publisher	Springer-Verlag
Publisher Date	2005-01-01
Publisher Place	New York
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Neurosciences Pharmaceutical Sciences/Technology Neurology Neurochemistry Pharmacology/Toxicology Neurobiology
Content Type	Text
Resource Type	Article
Subject	Neuroscience Toxicology

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Neurosteroids and glutamate toxicity in fibroblasts expressing human NMDA receptors

Molecular Determinants of Multiple Effects of Nickel on NMDA Receptor Channels

Nicotine and nicotinic system in hypoglutamatergic models of schizophrenia

Molecular targets of lead in brain neurotoxicity

NMDA antagonist and antipsychotic actions in cortico-subcortical circuits

Professional biographical sketch

The neurobiology of opiate tolerance, dependence and sensitization: Mechanisms of NMDA receptor-dependent synaptic plasticity

Neurotoxicity of methamphetamine and methylenedioxymethamphetamine

Neuroprotection against Aβ and glutamate toxicity by melatonin: Are GABA receptors involved?

NMDA receptors as targets of heavy metal interaction and toxicity

Similar Documents

Neurosteroids and glutamate toxicity in fibroblasts expressing human NMDA receptors

Molecular Determinants of Multiple Effects of Nickel on NMDA Receptor Channels

Nicotine and nicotinic system in hypoglutamatergic models of schizophrenia

Molecular targets of lead in brain neurotoxicity

NMDA antagonist and antipsychotic actions in cortico-subcortical circuits

Professional biographical sketch

The neurobiology of opiate tolerance, dependence and sensitization: Mechanisms of NMDA receptor-dependent synaptic plasticity

Neurotoxicity of methamphetamine and methylenedioxymethamphetamine

Neuroprotection against Aβ and glutamate toxicity by melatonin: Are GABA receptors involved?

NMDA receptors as targets of heavy metal interaction and toxicity