Mechanisms of ammonia-induced cell death in rat cortical neurons: Roles of NMDA receptors and glutathione

2005 ◽  
Vol 47 (1-2) ◽  
pp. 51-57 ◽  
Author(s):  
A KLEJMAN ◽  
M WEGRZYNOWICZ ◽  
E SZATMARI ◽  
B MIODUSZEWSKA ◽  
M HETMAN ◽  
...  
Keyword(s):  
Cell Death ◽  
Nmda Receptors ◽  
Cortical Neurons ◽  
Rat Cortical Neurons

Trapping Channel Block of NMDA-Activated Responses By Amantadine and Memantine

1997 ◽  
Vol 77 (1) ◽  
pp. 309-323 ◽  
Author(s):  
Thomas A. Blanpied ◽  
Faye A. Boeckman ◽  
Elias Aizenman ◽  
Jon W. Johnson
Keyword(s):  
Nmda Receptor ◽  
Nmda Receptors ◽  
Cortical Neurons ◽  
Chinese Hamster ◽  
Therapeutic Effects ◽  
Channel Block ◽  
Cultured Cortical Neurons ◽  
Simple Kinetic Model ◽  
Rat Cortical Neurons ◽  
Partial Trapping

Blanpied, Thomas A., Faye Boeckman, Elias Aizenman, and Jon W. Johnson. Trapping channel block of NMDA-activated responses by amantadine and memantine. J. Neurophysiol. 77: 309–323, 1997. We investigated the mechanisms by which the antiparkinsonian and neuroprotective agents amantadine and memantine inhibit responses to N-methyl-d-aspartic acid (NMDA). Whole cell recordings were performed using cultured rat cortical neurons or Chinese hamster ovary (CHO) cells expressing NMDA receptors. Both amantadine and memantine blocked NMDA-activated channels by binding to a site at which they could be trapped after channel closure and agonist unbinding. For neuronal receptors, the IC50s of amantadine and memantine at −67 mV were 39 and 1.4 μM, respectively. When memantine and agonists were washed off after steady-state block, one-sixth of the blocked channels released rather than trapped the blocker; memantine exhibited “partial trapping.” Thus memantine appears to have a lesser tendency to be trapped than do phencyclidine or (5R,10S)-(+)-5m e t h y l - 1 0 , 1 1 - d i h y d r o - 5 H - d i b e n z o [ 1 , d ] c y c l i h e p t e n - 5 , 1 0 - i m i n e(MK-801). We next investigated mechanisms that might underlie partial trapping. Memantine blocked and could be trapped by recombinant NMDA receptors composed of NR1 and either NR2A or NR2B subunits. In these receptors, as in the native receptors, the drug was released from one-sixth of blocked channels rather than being trapped in all of them. The partial trapping we observed therefore was not due to variability in the action of memantine on a heterogeneous population of NMDA receptors in cultured cortical neurons. Amantadine and memantine each noncompetitively inhibited NMDA-activated responses by binding at a second site with roughly 100-fold lower affinity, but this form of inhibition had little effect on the extent to which memantine was trapped. A simple kinetic model of blocker action was used to demonstrate that partial trapping can result if the presence of memantine in the channel affects the gating transitions or agonist affinity of the NMDA receptor. Partial trapping guarantees that during synaptic communication in the presence of blocker, some channels will release the blocker between synaptic responses. The extent to which amantadine and memantine become trapped after channel block thus may influence their therapeutic effects and their modulation of NMDA-receptor-mediated excitatory postsynaptic potentials.

scholarly journals Neuroprotection associated with alternative splicing of NMDA receptors in rat cortical neurons

2006 ◽  
Vol 147 (6) ◽  
pp. 622-633 ◽  
Author(s):  
Beate Jaekel ◽  
Katja Mühlberg ◽  
Susana Garcia de Arriba ◽  
Andreas Reichenbach ◽  
Ester Verdaguer ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Nmda Receptors ◽  
Cortical Neurons ◽  
Rat Cortical Neurons

scholarly journals PAC proton-activated chloride channel contributes to acid-induced cell death in primary rat cortical neurons

Channels ◽  
2020 ◽  
Vol 14 (1) ◽  
pp. 53-58 ◽  
Author(s):  
James Osei-Owusu ◽  
Junhua Yang ◽  
Maria Del Carmen Vitery ◽  
Mengnan Tian ◽  
Zhaozhu Qiu
Keyword(s):  
Cell Death ◽  
Chloride Channel ◽  
Cortical Neurons ◽  
Rat Cortical Neurons

α-lipoic acid protects rat cortical neurons against cell death induced by amyloid and hydrogen peroxide through the Akt signalling pathway

2001 ◽  
Vol 312 (3) ◽  
pp. 125-128 ◽  
Author(s):  
Lei Zhang ◽  
Gou qaing Xing ◽  
Jeffery L. Barker ◽  
Yoong Chang ◽  
Dragan Maric ◽  
...  
Keyword(s):  
Hydrogen Peroxide ◽  
Cell Death ◽  
Lipoic Acid ◽  
Cortical Neurons ◽  
Signalling Pathway ◽  
Rat Cortical Neurons
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