scholarly journals Voltage-dependent interaction of open-channel blocking molecules with gating of NMDA receptors in rat cortical neurons.

1996 ◽  
Vol 493 (2) ◽  
pp. 425-445 ◽  
Author(s):  
S M Antonov ◽  
J W Johnson
Keyword(s):  
Nmda Receptors ◽  
Cortical Neurons ◽  
Open Channel ◽  
Channel Blocking ◽  
Voltage Dependent ◽  
Rat Cortical Neurons ◽  
Dependent Interaction

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 Voltage-dependent block of fast chloride channels from rat cortical neurons by external tetraethylammonium ion.

1992 ◽  
Vol 100 (2) ◽  
pp. 217-231 ◽  
Author(s):  
D Y Sanchez ◽  
A L Blatz
Keyword(s):  
Ion Channels ◽  
Dose Response ◽  
Cortical Neurons ◽  
Sufficient Evidence ◽  
Dependent Manner ◽  
Response Relationship ◽  
Dose Response Relationship ◽  
Tetraethylammonium Ion ◽  
Voltage Dependent ◽  
Rat Cortical Neurons

Tetraethylammonium ion (TEA) and its longer chain derivatives have been used extensively to block currents through K-selective ion channels. Substantial information has been gained about the structure and gating mechanisms of K and other cation channels from the analysis of the blocking interactions of TEA and other quaternary ammonium ions. We now present an analysis of blocking interactions between single Cl-selective ion channels from acutely dissociated rat cortical neurons and externally applied TEA. TEA applied to the extracellular membrane surface (TEAo) blocked Cl channels in a voltage-dependent manner, with hyperpolarizing potentials favoring block. The voltage dependence of block could be adequately fit assuming that TEA enters the channel pore and binds to a site located approximately 28% of the way through the membrane electrical field. The dose-response relationship between fractional current and [TEA]o at a fixed holding potential of -40 mV was well fit to a simple model with two blocking sites with dissociation constants (Kd) of approximately 2 and 70 mM. The dose-response relationship could also be fit by a mechanism where TEA only partially blocks the channels. At the bandwidth used in these experiments (1-2 kHz), both the mean open duration (composed of the open and blocked durations) and burst duration (composed of open, blocked, and short lifetime shut durations) increased with increased [TEA]o. This is expected if TEAo can bind and unbind only when the channel is in the open kinetic state. These results suggest that the structure of the permeability pathway of these anion-selective channels may be very similar to that of other channels that are blocked by TEA. Additionally, these results caution that a blocking effect by TEA cannot, by itself, be used as sufficient evidence for implicating the participation of K channels in a particular process.

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.

Potassium currents in rat cortical neurons in culture are enhanced by the antiepileptic drug carbamazepine

1990 ◽  
Vol 68 (4) ◽  
pp. 545-547 ◽  
Author(s):  
C. Zona ◽  
V. Tancredi ◽  
E. Palma ◽  
G. C. Pirrone ◽  
M. Avoli
Keyword(s):  
Antiepileptic Drug ◽  
Antiepileptic Drugs ◽  
Cortical Neurons ◽  
Potassium Currents ◽  
Patch Clamping ◽  
Partial Seizures ◽  
Complex Partial Seizures ◽  
Voltage Dependent ◽  
Rat Neocortex ◽  
Rat Cortical Neurons

We report that carbamazepine (Tegretol), a drug that is useful for the treatment of complex partial seizures, enhances outward, voltage-dependent K+ currents generated by rat neocortical cells in culture and recorded with patch-clamping techniques. This effect is seen in the presence of therapeutic concentrations of carbamazepine (10–20 μM). Furthermore, at these doses carbamazepine does not influence voltage-dependent inward Na+ and Ca2+ currents recorded in these cells. The action exerted by carbamazepine on K+ currents is a novel finding and might represent an important mechanism for controlling neocortical excitability and thus the generation of epileptiform activity.Key words: potassium currents, antiepileptic drugs, carbamazepine, rat neocortex.

Sign in / Sign up

Export Citation Format

Share Document