1. Whole-cell current through heteromeric NR1-NR2A and NR1-NR2B subunit combinations of NMDA channels transiently expressed in human embryonic kidney cells (HEK 293) were studied using the patch-clamp technique. 2. With 4 mM Mg-ATP in the internal pipette solution, the responses of cells expressing NR1-NR2A channels to glutamate application gradually decreased, reaching 50% of control during the first 20 min of recording. This process was accompanied by acceleration of desensitization. 3. Conditioning (5-15 s) applications of glutamate (100 microM) induced a transient inactivation of NR1-NR2A and NR1-NR2B channels (20-40%) with a slow time course of recovery (tau r = 10-60 s). Both the degree of inactivation and the time constant of recovery increased with the duration of conditioning applications of glutamate, and with an elevation of Ca2+ in the external solution. 4. These results show that both NR1-NR2A and NR1-NR2B recombinant NMDA receptor-channels expressed in HEK 293 cells can be transiently inhibited by Ca2+ ions in a similar way to that described for hippocampal neurones.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1157782PMC
http://dx.doi.org/10.1113/jphysiol.1995.sp020540DOI Listing

Publication Analysis

Top Keywords

nr1-nr2a nr1-nr2b
12
nmda receptor-channels
8
receptor-channels expressed
8
expressed human
8
human embryonic
8
embryonic kidney
8
kidney cells
8
hek 293
8
applications glutamate
8
calcium-dependent inactivation
4

Similar Publications

Amyloid Beta Oligomers-Induced Ca Entry Pathways: Role of Neuronal Networks, NMDA Receptors and Amyloid Channel Formation.

Biomedicines

May 2022

Unidad de Excelencia Instituto de Biología y Genética Molecular (IBGM), Universidad de Valladolid and Consejo Superior de Investigaciones Científicas (CSIC), 47003 Valladolid, Spain.

The molecular basis of amyloid toxicity in Alzheimer's disease (AD) remains controversial. Amyloid β (Aβ) oligomers promote Ca influx, mitochondrial Ca overload and apoptosis in hippocampal neurons in vivo and in vitro, but the primary Ca entry pathways are unclear. We studied Ca entry pathways induced by Aβ oligomers in rat hippocampal and cerebellar neurons.

View Article and Find Full Text PDF

We had previously reported that neuroinflammation and memory impairment associated with intracerebroventricular streptozotocin (ICV STZ) injection in rats was due to glial activation and modulation of the N-methyl-D-aspartate (NMDA) receptor function. However, the exact role of the NMDA receptor and the molecules associated with downstream calcium ion signaling in STZ-induced astroglial activation is not known. Thus, in the present study, Memantine (an NMDA receptor antagonist) and Ibuprofen (an anti-inflammatory drug) were used as the pharmacological tool to investigate the molecular mechanisms involved in STZ-induced astroglial inflammation.

View Article and Find Full Text PDF

The neuroprotective effects of resveratrol against excitatory neurotoxicity have been associated with N-methyl-D-aspartate receptor (NMDAR) inhibition. This study examined the differential inhibitory effects of resveratrol on NMDAR-mediated responses in neuronal cells with different NMDAR subtype composition. The effects of resveratrol on NMDA-induced cell death and calcium influx in immature and mature rat primary cortical neurons were determined and compared.

View Article and Find Full Text PDF

Glycine transporter inhibitors: A new avenue for managing neuropathic pain.

Brain Res Bull

October 2019

Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, Semmelweis University, Nagyvarad ter 4, P.O. Box 370, H-1445 Budapest, Hungary.

Interneurons operating with glycine neurotransmitter are involved in the regulation of pain transmission in the dorsal horn of the spinal cord. In addition to interneurons, glycine release also occurs from glial cells neighboring glutamatergic synapses in the spinal cord. Neuronal and glial release of glycine is controlled by glycine transporters (GlyTs).

View Article and Find Full Text PDF

Extracellular mild acidosis decreases the Ca permeability of the human NMDA receptors.

Cell Calcium

June 2019

Dipartimento di Fisiologia e Farmacologia "V. Erspamer", Sapienza Università di Roma, Rome, Italy; IRCCS Neuromed, Pozzilli, Italy. Electronic address:

NMDA receptors (NMDARs) are glutamate-gated ion channels involved in excitatory synaptic transmission and in others physiological processes such as synaptic plasticity and development. The overload of Ca ions through NMDARs, caused by an excessive activation of receptors, leads to excitotoxic neuronal cell death. For this reason, the reduction of Ca flux through NMDARs has been a central focus in finding therapeutic strategies to prevent neuronal cell damage.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!