N-methyl-d-aspartate-evoked adenosine and inosine release from neurons requires extracellular calciumThis article is one of a selection of papers published in a special issue celebrating the 125th anniversary of the Faculty of Medicine at the University of Manitoba.

2009 ◽  
Vol 87 (10) ◽  
pp. 850-858 ◽  
Author(s):  
Christina R. Zamzow ◽  
Ratna Bose ◽  
Fiona E. Parkinson
Keyword(s):  
Nmda Receptors ◽  
Cortical Neurons ◽  
Nucleoside Transporter ◽  
Stroke Models ◽  
Intracellular Ca ◽  
125Th Anniversary ◽  
Rat Cortical Neurons ◽  
Dependent Protein ◽  
Potent Antagonist ◽  
The University

The nucleoside adenosine (ADO) is a neuromodulator in brain. ADO and its metabolite inosine (INO) have been shown to increase cell viability in stroke models. During ischemia, extracellular levels of both ADO and INO are increased. In this study, we treated rat cortical neurons with N-methyl-d-aspartate (NMDA) to initiate excitotoxicity and then investigated the mechanisms of ADO and INO release. NMDA induced a significant increase in ADO and INO production. The effect of NMDA receptor antagonists on NMDA-evoked ADO and INO release was examined. MK-801 (1 µmol/L), a potent antagonist that lacks receptor subunit selectivity, completely blocked evoked release of both ADO and INO. Memantine (10 µmol/L), a lower affinity antagonist that also lacks subunit selectivity, blocked INO, but not ADO, release. Ifenprodil (10 µmol/L), an inhibitor selective for NMDA receptors containing the NR2B subunit, completely blocked evoked ADO and INO release. NVP-AAM077 (NVP, 0.4 µmol/L), an inhibitor selective for NMDA receptors containing the NR2A subunit, did not significantly block evoked release of either ADO or INO. Removal of extracellular Ca2+ abolished NMDA-evoked release of both ADO and INO. BAPTA (25 µmol/L), which chelates intracellular Ca2+, had no significant effect on either ADO or INO release unless extracellular Ca2+ was also removed. Inhibitors of Ca2+/calmodulin-dependent protein kinase II (CaMKII) prevented NMDA-evoked ADO and INO release and decreased nucleoside transporter function. These data indicate that NMDA-evoked ADO and INO release is dependent on subunit composition of NMDA receptors. As well, NMDA-evoked ADO and INO release requires nucleoside transporters and extracellular Ca2+ and is enhanced by activation of CaMKII.

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

Effects of Antidepressants on γ-Aminobutyric Acid- and N-Methyl-D-Aspartate-Induced Intracellular Ca2+ Concentration Increases in Primary Cultured Rat Cortical Neurons

2000 ◽  
Vol 42 (3) ◽  
pp. 120-126 ◽  
Author(s):  
Minoru Takebayashi ◽  
Ariyuki Kagaya ◽  
Masatoshi Inagaki ◽  
Tosiro Kozuru ◽  
Hiroaki Jitsuiki ◽  
...  
Keyword(s):  
Cortical Neurons ◽  
Aminobutyric Acid ◽  
Intracellular Ca ◽  
Rat Cortical Neurons

scholarly journals Nicotinic modulation of Ca2+ oscillations in rat cortical neurons in vitro

2016 ◽  
Vol 310 (9) ◽  
pp. C748-C754 ◽  
Author(s):  
JianGang Wang ◽  
YaLi Wang ◽  
FangLi Guo ◽  
ZhiBo Feng ◽  
XiangFang Wang ◽  
...  
Keyword(s):  
Nicotinic Acetylcholine Receptors ◽  
Cortical Neurons ◽  
Oscillation Frequency ◽  
Acetylcholine Receptors ◽  
Nicotinic Acetylcholine ◽  
Cultured Cortical Neurons ◽  
Intracellular Ca ◽  
Rat Cortical Neurons ◽  
20 Nm

The roles of nicotine on Ca2+ oscillations [intracellular Ca2+ ([Ca2+]i) oscillation] in rat primary cultured cortical neurons were studied. The spontaneous [Ca2+]i oscillations (SCO) were recorded in a portion of the neurons (65%) cultured for 7–10 days in vitro. Application of nicotine enhanced [Ca2+]i oscillation frequency and amplitude, which were reduced by the selective α4β2-nicotinic acetylcholine receptors (nAChRs) antagonist dihydro-β-erythroidine (DHβE) hydrobromide, and the selective α7-nAChRs antagonist methyllycaconitine citrate (MLA, 20 nM). DHβE reduced SCO frequency and prevented the nicotinic increase in the frequency. DHβE somewhat enhanced SCO amplitude and prevented nicotinic increase in the amplitude. MLA (20 nM) itself reduced SCO frequency without affecting the amplitude but blocked nicotinic increase in [Ca2+]i oscillation frequency and amplitude. Furthermore, coadministration of both α4β2- and α7-nAChRs antagonists completely prevented nicotinic increment in [Ca2+]i oscillation frequency and amplitude. Thus, our results indicate that both α4β2- and α7-nAChRs mediated nicotine-induced [Ca2+]i oscillations, and two nAChR subtypes differentially regulated SCO.

Mitochondrial transport in processes of cortical neurons is independent of intracellular calcium

2006 ◽  
Vol 291 (6) ◽  
pp. C1193-C1197 ◽  
Author(s):  
Luis Beltran-Parrazal ◽  
Héctor E. López-Valdés ◽  
K. C. Brennan ◽  
Mauricio Díaz-Muñoz ◽  
Jean de Vellis ◽  
...  
Keyword(s):  
Cortical Neurons ◽  
Action Potentials ◽  
Synaptic Activity ◽  
Action Potential Firing ◽  
Mitochondrial Movement ◽  
Neuronal Processes ◽  
Potential Firing ◽  
Intracellular Ca ◽  
Rat Cortical Neurons ◽  
And Function

Mitochondria show extensive movement along neuronal processes, but the mechanisms and function of this movement are not clearly understood. We have used high-resolution confocal microscopy to simultaneously monitor movement of mitochondria and changes in intracellular [Ca2+] ([Ca2+]i) in rat cortical neurons. A significant percentage (27%) of the total mitochondria in cortical neuronal processes showed movement over distances of >2 μM. The average velocity was 0.52 μm/s. The velocity, direction, and pattern of mitochondrial movement were not affected by transient increases in [Ca2+]i associated with spontaneous firing of action potentials. Stimulation of Ca2+ transients with forskolin (10 μM) or bicuculline (10 μM), or sustained elevations of [Ca2+]i evoked by glutamate (10 μM) also had no effect on mitochondrial transit. Neither removal of extracellular Ca2+, depletion of intracellular Ca2+ stores with thapsigargin, or inhibition of synaptic activity with TTX (1 μM) or a cocktail of CNQX (10 μM) and MK801 (10 μM) affected mitochondrial movement. These results indicate that movement of mitochondria along processes is a fundamental activity in neurons that occurs independently of physiological changes in [Ca2+]i associated with action potential firing, synaptic activity, or release of Ca2+ from intracellular stores.

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