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Vladimir Farar,
Franziska Mohr,
Marie Legrand,
Boris Lamotte d'Incamps,
Jan Cendelin,
Jacqueline Leroy,
Marc Abitbol,
Veronique Bernard,
Frédéric Baud,
Vincent Fournet,
Pascal Houze,
Jochen Klein,
Benoit Plaud,
Jan Tuma,
Martina Zimmermann, Philippe Ascher,
Anna Hrabovska,
Jaromir Myslivecek,
Eric Krejci
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ABSTRACT: Acetylcholinesterase (AChE) rapidly hydrolyzes acetylcholine. At the neuromuscular junction, AChE is mainly anchored in the extracellular matrix by the collagen Q, whereas in the brain, AChE is tethered by the proline-rich membrane anchor (PRiMA). The AChE-deficient mice, in which AChE has been deleted from all tissues, have severe handicaps. Surprisingly, PRiMA KO mice in which AChE is mostly eliminated from the brain show very few deficits. We now report that most of the changes observed in the brain of AChE-deficient mice, and in particular the high levels of ambient extracellular acetylcholine and the massive decrease of muscarinic receptors, are also observed in the brain of PRiMA KO. However, the two groups of mutants differ in their responses to AChE inhibitors. Since PRiMA-KO mice and AChE-deficient mice have similar low AChE concentrations in the brain but differ in the AChE content of the peripheral nervous system, these results suggest that peripheral nervous system AChE is a major target of AChE inhibitors, and that its absence in AChE- deficient mice is the main cause of the slow development and vulnerability of these mice. At the level of the brain, the adaptation to the absence of AChE is nearly complete.
Journal of Neurochemistry 07/2012; 122(5):1065-80. · 4.06 Impact Factor
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ABSTRACT: At the cerebellar synapse between the parallel fibers (PFs) and the Purkinje cells in the cerebellum, we have found that application of N-methyl-d-aspartate (NMDA) reversibly depresses the postsynaptic current. We present evidence that this depression involves NMDA receptors located on the presynaptic axons and requires that the NMDA application be combined with action potentials in the PFs. Unexpectedly, unlike other modulations mediated by presynaptic receptors, the NMDA-induced inhibition does not involve a depression of transmitter release. Because it is blocked by both nitric oxide synthase and soluble guanylate cyclase inhibitors, we propose that it involves a trans-synaptic mechanism in which NO released by the PFs decreases the glutamate sensitivity of the Purkinje cell.
Proceedings of the National Academy of Sciences 11/2000; 97(21):11593-7. · 9.68 Impact Factor
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ABSTRACT: 1. Two classes of amphiphilic compounds, lysophospholipids and arachidonic acid, have been suggested to produce opposite deformations of the lipid bilayer. We have found that their effects on N-methyl-D-aspartate (NMDA) responses are opposite, and resemble those of mechanical deformations of the plasma membrane. 2. Lysophospholipids inhibited NMDA responses both in nucleated patches taken from cultured neurons and in cells expressing recombinant NMDA receptors. This inhibition was reversible, voltage independent and stronger at non-saturating doses of agonist. It was not linked to the charge of the polar head, and was not mimicked by lysophosphatidic acid or phosphatidylcholine. In outside-out patches, lysophospholipids reduced the open probability of NMDA-activated channels without changing their single-channel conductance. 3. The inhibition produced by lysophospholipids occluded that produced by a mechanical compression induced by changes in osmotic or hydrostatic pressure. 4. The potentiation of NMDA responses by arachidonic acid was observed both in native and recombinant receptors, including those in which the putative 'fatty acid binding domain' had been deleted. This suggests that, like lysophospholipids, arachidonic acid alters the NMDA receptor by insertion into the lipid bilayer. 5. Recombinant receptors in which the cytoplasmic tails had been modified or deleted were still sensitive to mechanical deformation. A linkage to the cytoskeleton is therefore not required for NMDA receptor mechanosensitivity. 6. The fact that the NMDA responses are depressed similarly by compression and lysophospholipids, and potentiated similarly by stretch and arachidonic acid supports the notion that the modulation of NMDA receptor activity by asymmetrical amphiphilic compounds involves pressure changes transmitted through the lipid bilayer. Compounds with a large hydrophilic head mimic the effects of a compression, and compounds with a small hydrophilic head mimic the effects of stretch.
The Journal of Physiology 01/1999; 513 ( Pt 2):317-30. · 4.72 Impact Factor
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ABSTRACT: Glycine uptake governs glycine site occupancy at NMDA receptors of excitatory synapses. J. Neurophysiol. 80: 3336-3340, 1998. At central synapses occupation of glycine binding sites of N-methyl--aspartate receptors (NMDA-Rs) is a necessary prerequisite for the excitatory neurotransmitter glutamate to activate these receptors. There is conflicting evidence as to whether glycine binding sites normally are saturated. If they are not, then alterations in local glycine concentration could modulate excitatory synaptic transmission. By using an in vitro brain stem slice preparation we investigated whether the glycine site is saturated for synaptically activated NMDA-Rs in neonatal rat hypoglossal motoneurons. We found that the NMDA-R-mediated component of spontaneous miniature excitatory postsynaptic currents could be potentiated by exogenously applied glycine as well as by -serine. The effects of glycine were observed only at concentrations (100 microM or more) two orders of magnitude above the apparent dissociation constant of glycine from NMDA receptors. In contrast, -serine, a nontransported NMDA-R glycine site agonist, was effective in the low micromolar range, i.e., at concentrations similar to those found to be effective on isolated cells or on outside-out patches. We conclude that at these synapses the glycine concentration around synaptic NMDA-Rs is set below the concentration required to saturate their glycine site and is likely to be stabilized by a powerful glycine transport mechanism.
Journal of Neurophysiology 01/1999; 80(6):3336-40. · 3.32 Impact Factor
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ABSTRACT: 1. The NMDA receptor channel is blocked by both external and internal Mg2+ ions, which are assumed to bind inside the channel on each side of a central barrier. We have analysed the internal Mg2+ block in recombinant NR1-NR2A NMDA receptors expressed in Xenopus oocytes. We have determined the effects of mutations of two asparagines that line the selectivity filter of the channel, one located within the NR1 subunit (N598) and the other within the NR2A subunit (N596). 2. The whole-cell current-voltage relation of wild-type NMDA channels shows inward rectification that reflects the voltage-dependent block produced by the internal Mg2+ of the oocyte. This inward rectification is slightly reduced in the NR2 mutant (N596S) but is abolished in the NR1 mutants (N598Q and N598S). This suggests that the NR1 asparagine plays a larger role than the NR2 asparagine in controlling the internal Mg2+ block. 3. Single-channel current-voltage relations confirm that the internal Mg2+ block is reduced in both the NR1 and NR2 mutants. However, the reduction is small and is similar for the two families of mutants. 4. The discrepancy between whole-cell and single-channel data is partly due to differential effects of internal Mg2+ on the open probabilities of the two conductance states present in NR1 mutant channels. 5. The results suggest that mutations of NR1 and NR2 asparagines lower the central barrier to Mg2+. An additional contribution of the NR2 asparagine to the external Mg2+ binding site (and possibly to the external barrier that controls access to this site) may account for the marked relief of external Mg2+ block produced by the NR2 mutation.
The Journal of Physiology 03/1998; 507 ( Pt 1):1-12. · 4.72 Impact Factor
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ABSTRACT: Micromolar concentrations of extracellular Zn2+ are known to antagonize native NMDA receptors via a dual mechanism involving both a voltage-independent and a voltage-dependent inhibition. We have tried to evaluate the relative importance of these two effects and their subunit specificity on recombinant NMDA receptors expressed in HEK 293 cells and Xenopus oocytes. The comparison of NR1a-NR2A and NR1a-NR2B receptors shows that the voltage-dependent inhibition is similar in both types of receptors but that the voltage-independent inhibition occurs at much lower Zn2+ concentrations in NR1a-NR2A receptors (IC50 in the nanomolar range) than in NR1a-NR2B receptors (IC50 in the micromolar range). The high affinity of the effect observed with NR1a-NR2A receptors was found to be attributable mostly to the slow dissociation of Zn2+ from its binding site. By analyzing the effects of Zn2+ on varied combinations of NR1 (NR1a or NR1b) and NR2 (NR2A, NR2B, NR2C), we show that both the NR1 and the NR2 subunits contribute to the voltage-independent Zn2+ inhibition. We have observed further that under control conditions, i.e., in zero nominal Zn2+ solutions, the addition of low concentrations of heavy metal chelators markedly potentiates the responses of NR1a-NR2A receptors, but not of NR1a-NR2B receptors. This result suggests that traces of a heavy metal (probably Zn2+) contaminate standard solutions and tonically inhibit NR1a-NR2A receptors. Chelation of a contaminant metal also could account for the rapid NR2A subunit-specific potentiations produced by reducing compounds like DTT or glutathione.
Journal of Neuroscience 09/1997; 17(15):5711-25. · 7.11 Impact Factor
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ABSTRACT: We report a strong coupling between permeation and gating in a mutant NMDA channel (NR1 N598Q-NR2A). The channel opens to two states that differ by their conductance and, surprisingly, by their selectivity for two permeant monovalent cations, Na+ and Cs+. The two open states are linked to the closed state via a cyclic gating reaction that proceeds preferentially in one direction under biionic conditions, indicating that the gating mechanism is not at equilibrium. The direction and the magnitude of this gating asymmetry can be accounted for by assuming that ions bound to a site in the permeation pathway influence the gating of this mutant channel, and that in the closed state, the channel site is accessible to internal cations.
Neuron 02/1997; 18(1):167-77. · 14.74 Impact Factor
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ABSTRACT: Mg2+ ions block N-methyl-D-aspartate (NMDA) channels by entering the pore from either the extracellular or the cytoplasmic side of the membrane in a voltage-dependent manner. We have used these two different block phenomena to probe the structure of the subunits forming NMDA channels. We have made several amino acid substitutions downstream of the Q/R/N site in the TMII region of both NR1 and NR2A subunits. Mutant NR1 subunits were coexpressed with wild-type NR2A subunits and vice versa in Xenopus oocytes. We found that individually mutating the first two amino acid residues downstream to the Q/R/N site affects mostly the block by external Mg2+. Mutations of residues five to seven positions downstream of the Q/R/N site do not influence the external Mg2+ block, but clearly influence the block by internal Mg2+. These data add support to the hypothesis that there are two separate binding sites for external and internal Mg2+ block. They also indicate that the C-terminal end of TMII contributes to the inner vestibule of the pore of NMDA channels and thus provide additional evidence that TMII forms a loop that reemerges toward the cytoplasmic side of the membrane.
Proceedings of the National Academy of Sciences 09/1996; 93(16):8648-53. · 9.68 Impact Factor
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ABSTRACT: Extracellular Mg2+, which blocks NMDA channels in a voltage-dependent manner and increases the receptor's affinity for glycine, is shown here to potentiate NMDA responses at saturating glycine concentrations. This potentiation, induced by millimolar concentrations of Mg2+, is not mimicked by Ca2+ and Ba2+ and is voltage independent. The potentiation is variable in native receptors of cultured mouse central neurons; in recombinant receptors, it is "permitted" by the NR2B subunit and prevented by the NR1 splice variant containing an N-terminal insert. Mg2+ also induces a shift of the pH sensitivity of NMDA receptors. The similarity and nonadditivity of the effects of Mg2+ and spermine suggest that Mg2+ may be the physiological agonist acting at the subunit-specific spermine site.
Neuron 12/1995; 15(5):1109-20. · 14.74 Impact Factor
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ABSTRACT: Changes in osmotic and hydrostatic pressure were found to modulate NMDA responses of cultured embryonic mouse neurons recorded in various patch-clamp configurations. In nucleated patches, NMDA currents were potentiated by reductions in external osmolarity and were reduced in hyper-osmotic solutions. These changes, which were greater for low concentrations of NMDA, were not observed for responses to kainate, glycine, or GABA. They could be mimicked by directly changing the pipette pressure in nucleated, outside-out, inside-out, and cell-attached patches. Osmosensitivity of NMDA responses was also observed in the whole-cell mode, but only after prolonged dialysis. Mechanosensitivity of NMDA receptors could have an important role in neuronal regions experiencing changes in membrane tension, such as spines or growth cones.
Neuron 10/1994; 13(3):645-55. · 14.74 Impact Factor
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ABSTRACT: 1. The characteristics of the activation of the N-methyl-D-aspartate (NMDA) response by glycine were studied using whole-cell and outside-out patch clamp recording techniques. 2. Glycine concentration-response (C-R) curves were measured in the presence of 10 microM-NMDA and fitted with the Hill equation modified to account for the response to NMDA observed in the absence of added glycine. The mean value of the apparent dissociation constant (KD) was 150 nM, and the mean value of the Hill coefficient (nH) was 1.1. When the KD was corrected for the concentration of contaminating glycine in nominally glycine-free solutions, estimated assuming that there is no response in the absence of glycine, the value was 130 nM. 3. The question of how many glycine binding sites there are on each NMDA receptor-channel complex was addressed by examining the curvature at the foot of the glycine C-R curve. An equation that allowed estimation of both the concentration of contaminating glycine and of the value of nH was fitted to glycine C-R data up to 50 nM. The mean value of nH was found to be 1.0, consistent with the idea that there is one glycine binding site. 4. The kinetics of the interaction of glycine with the NMDA receptor were measured by fitting single exponential curves to the current relaxation following a jump in glycine concentration in the presence of 10 microM-NMDA. The plot of the inverse of the relaxation time constant as a function of glycine concentration after the concentration jump was linear. The association rate constant was estimated from these data as 1.2 x 10(7) M-1 s-1 and the dissociation rate as 1.0 s-1. 5. Experiments were devised to allow the evaluation of the KD and dissociation rates of glycine in the absence of NMDA. They led to a value for KD of 80 nM, slightly but significantly lower than the value of 150 nM estimated in the presence of 10 microM-NMDA. The glycine dissociation rate in the absence of NMDA was found to be 0.7 s-1, not significantly different from that measured in the presence of 10 microM-NMDA. 6. The results are consistent with a model of the NMDA receptor with a single glycine binding site. The characteristics of glycine binding are similar in the absence and the presence of 10 microM-NMDA, although NMDA binding may cause a small increase in the glycine KD.(ABSTRACT TRUNCATED AT 250 WORDS)
The Journal of Physiology 10/1992; 455:339-65. · 4.72 Impact Factor
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ABSTRACT: A series of substituted [phosphono-, sulfo-, carboxy-, and (N-hydroxycarbamoyl)methyl]phenylalanines were synthesized as probes for the investigation of the preferred antagonist state of the NMDA receptor antagonists. The potency of these compounds was evaluated by measuring electrophysiological responses induced by NMDA in cultured mouse cortical neurons. 3-(Phosphonomethyl)phenylalanine [1(m)] a formal AP7 analogue, has been shown to be the most potent antagonist in this study with an IC50 of around 5 microM. The isomeric 2-(phosphonomethyl)phenylalanine [1(o)] was about half as active as 1(m) and as active as compound 5(3), a derivative which is cis-hydrogenated on the phenyl ring of 1(m). Replacement of a phosphono by a sulfo group led to a large reduction in the ability of these compounds to antagonize NMDA responses, although the ortho and meta isomers retained some activity in their reduced forms. In both series the para isomers were almost completely inactive at 100 microM. Introduction of a carboxyl or a bidentate HONHCO group in place of the phosphono moiety in the 3-position results in compounds devoid of activity. The active and inactive compounds of this study were used in conjunction with the most potent linear and cyclic phosphono-containing NMDA antagonists reported to date to determine, via computer modeling techniques, a three-dimensional model corresponding to a antagonist preferring state of the NMDA binding site. This structure defines a pharmacophore which is characterized by (i) well-defined distances between the central atoms of the polar groups PO3H-, NHn+, (n = 2, 3), and COO- (P-N = 5.89 +/- 0.12 A, P-C = 6.66 +/- 0.08 A, and N-C = 2.28 +/- 0.01 A), (ii) a sterically allowed region between the C5 methylene and the PO3H- group, and (iii) a molecular electrostatic field in which the positive, neutral, and negative potential zones are self-contained--with the negative potential zone connecting the PO3H- and COO- groups as the largest. We have compared our results to a preliminary model of the NMDA antagonist site by Hutchison et al. and to a topological model of the NMDA-glycine receptor site by Cordi et al. Our proposed steric-electrostatic pharmacophore which refines, simplifies, and improves these models has now to be validated by the design of new NMDA antagonists.
Journal of Medicinal Chemistry 08/1992; 35(14):2551-62. · 5.25 Impact Factor
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ABSTRACT: 1. Activation and desensitization of N-methyl-D-aspartate (NMDA) receptors were studied in large outside-out patches excised from cultured embryonic neurones dissociated from mouse forebrain. The patches were exposed to rapid changes of NMDA or L-glutamate concentrations in the presence of glycine at concentrations (10-20 microM) saturating the modulatory site of the NMDA receptor. 2. Immediately after formation of the patch the responses to NMDA and L-glutamate showed a slow and small desensitization, even with high concentrations of agonist. During the following hour, the peak response either decreased or remained relatively stable, but in all cases the desensitization increased and accelerated until it stabilized. In this 'stabilized' state, the desensitization produced by high concentrations of NMDA (1 mM) or L-glutamate (300 microM) had an exponential time course, with a time constant of about 30 ms. The ratio of the peak over the steady-state current was in the order of 40 for NMDA and about 30 for L-glutamate. 3. Concentration-response curves were built for the peak and the plateau responses, for NMDA and for L-glutamate. The comparison of these curves indicated that (i) the EC50 of the peak (K(app) was always higher than the EC50 of the plateau (Kss); (ii) the two EC50 values for NMDA (K(app) and Kss) were higher than those for L-glutamate; (iii) the Hill coefficient was close to 1.4 for each of the four curves. 4. The application of NMDA or L-glutamate at a low concentration for 3 s periods reduced the response to a subsequent application of the same agonist at a saturating concentration. The IC50 of this 'predesensitization', termed Kpre, was lower than the EC50 of the steady-state response, Kss. 5. The onset rates of desensitization increased with the concentration of agonist. The EC50 of this relation was close to the value of K(app). 6. The decay of the currents at the end of a 3 s application of agonist was usually well described by the sum of two exponentials both of which were faster for NMDA than for L-glutamate. 7. The recovery from desensitization after a long (3 s) pulse of agonist was approximately exponential, with a time constant of about 0.5 s for NMDA and about 3.5 s for L-glutamate.(ABSTRACT TRUNCATED AT 400 WORDS)
The Journal of Physiology 06/1992; 450:643-72. · 4.72 Impact Factor
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Comptes Rendus de l Académie des Sciences - Series III - Sciences de la Vie 02/1992; 314(9 Suppl):75-7.
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ABSTRACT: 1. Kynurenate (Kyn), 7-chlorokynurenate (7-Cl-Kyn), 3-amino-1-hydroxypyrrolid-2-one (HA-966) and D-cycloserine are known to bind to the glycine site that modulates the N-methyl-D-aspartate (NMDA) response of vertebrate central neurones. The effects of these compounds were investigated with patch-clamp and fast-perfusion techniques on mouse cortical neurones in primary culture in an effort to establish whether they act as antagonists, partial agonists and/or inverse agonists of glycine. A fast drug application method allowed the study of both steady-state and transient responses. 2. The analysis of steady-state responses indicates that the main effects of Kyn and 7-Cl-Kyn are those expected from competitive antagonists of glycine, with a dissociation constant of 15 microM for Kyn, and of 0.3 microM for 7-Cl-Kyn. Concentration jumps indicate that at all concentrations of glycine, and in particular in the absence of added glycine, the blockade by Kyn and 7-Cl-Kyn develops at a rate which is close to the rate of dissociation of glycine from its binding site and is independent of antagonist concentration. 3. The main effects of D-cycloserine and of HA-966 are those of partial agonists of high and low efficacy, respectively. In the absence of added glycine, D-cycloserine always produced a potentiation, while HA-966 produced either a potentiation or an inhibition. This can be explained by assuming the presence of a variable level of contaminating glycine. With both D-cycloserine and HA-966, concentration jumps produced biphasic relaxations in which the onset rate of the slow component was, here again, close to the rate of dissociation of glycine from its binding site. 4. These results can be interpreted by assuming that (1) Kyn and 7-Cl-Kyn are competitive antagonists of glycine, (2) HA-966 and D-cycloserine are partial agonists, (3) in the absence of added glycine some glycine is present in the extracellular solution and (4) the response in the total absence of glycine is very small or negligible.
The Journal of Physiology 12/1990; 430:189-212. · 4.72 Impact Factor
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ABSTRACT: The influence of glycine on the desensitization of NMDA-induced currents was studied using cultured embryonic mouse neurons. Although glycine often appeared to reduce desensitization in the whole-cell mode, it had no effect on desensitization in outside-out patches. Various interpretations can be proposed for this discrepancy, such as the presence in intact cells of an intracellular factor regulating desensitization, or the masking of desensitization in intact cells by restricted diffusion of the agonist in the extracellular space. The fact that glycine potentiates the NMDA responses under conditions where it does not regulate desensitization indicates that the potentiation cannot be explained by a reduction of desensitization.
Neuron 06/1990; 4(5):725-31. · 14.74 Impact Factor
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ABSTRACT: The N-methyl-D-aspartate (NMDA)-activated channel, which is known to be blocked by extracellular Mg ions, is shown also to be blocked by intracellular Mg ions. The block by intracellular Mg can be explained by assuming that Mg ions from the intracellular side enter the membrane electrical field before binding to the blocking site. The dissociation constant of the binding site for intracellular Mg is 8 mM at 0 mV, which is close to the value previously calculated for the extracellular Mg blocking site. The unbinding rates of intracellular and extracellular Mg are different, and their effects are additive, suggesting that the corresponding binding sites are distinct. Both blocks occur at physiological concentrations of Mg, making the NMDA-activated channel a bidirectional rectifier.
Biophysical Journal 06/1990; 57(5):1085-90. · 3.65 Impact Factor
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P Ascher
Advances in experimental medicine and biology 02/1990; 268:13-6. · 1.09 Impact Factor
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ABSTRACT: Patch-clamp recording techniques were used to study the properties of amino acid-activated channels in cultured "organotypic" slices from rat cerebellum and hippocampus. Hippocampal pyramidal cells responded to the three main glutamatergic agonists, N-methyl-D-aspartate (N-Me-D-Asp), quisqualate, and kainate, whereas Purkinje cells responded only to quisqualate and kainate. Analysis of single-channel events recorded in outside-out patches from hippocampal neurons showed large conductance events (50 pS), which occurred more frequently in the presence of glycine. These events could be produced by N-Me-D-Asp and also, at low frequency, by quisqualate. On the other hand, 50-pS events were never observed in Purkinje neurons. This supports the hypothesis that N-Me-D-Asp and "non-N-Me-D-Asp" receptors are distinct molecular entities. Comparison of whole-cell and outside-out patch recordings from Purkinje cells revealed a clear spatial segregation of gamma-aminobutyric acid (GABA) and glutamate receptors: although GABA receptors are found at high density in somatic membrane, quisqualate and kainate receptors are mostly extrasomatic. The results show that organotypic slice cultures are amenable to patch-clamp methods. They also show that, in these cultures, amino acids receptors have specific distribution patterns according to cell type and to region within a cell.
Proceedings of the National Academy of Sciences 06/1988; 85(9):3221-5. · 9.68 Impact Factor
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ABSTRACT: 1. The whole-cell and outside-out configurations of the patch-clamp method were used to investigate the properties of the channels activated by N-methyl-D-aspartate (NMDA channels) in mouse central neurones in culture. Recording was made in Mg2+-free solutions. 2. In the whole-cell recording mode the currents induced by both NMDA and L-glutamate were accompanied by a large increase in noise. In both cases the noise power spectra were well fitted by single Lorentzian functions and the corresponding mean time constant, tau, was about 6 ms at room temperature. The single-channel conductance, gamma n, estimated from the ratio of the noise variance to the total current, varied between 22 and 40 pS. 3. Endogenous amino acids known to activate NMDA receptors (L-glutamate, L-aspartate, L-cysteine sulphinate and quinolinate) as well as exogenous NMDA agonists such as ibotenate and trans-2,3-piperidine dicarboxylate (trans-PDA) all produced similar responses. In particular, analysis of the current noise yielded tau values between 4 and 8 ms in all cases. 4. NMDA responses were antagonized by 2-amino-5-phosphonovalerate (APV) without any effect on gamma n or tau values measured by noise analysis; NMDA responses were also diminished by D-alpha-aminoadipate and cis-2,3-piperidine dicarboxylate. 5. In outside-out patches, it was observed that the single-channel current amplitude varies linearly as a function of membrane potential between -80 and +60 mV. The reversal potential is near 0 mV. NMDA channels are permeable to Na+, K+ and Cs+, but blocked by choline. The single-channel conductance, gamma e, varies between 40 and 50 pS at room temperature. 6. The NMDA channels open in bursts of short openings interrupted by brief closures. At -60 mV, the closures had a mean duration, tc, of 0.4 +/- 0.2 ms. The mean channel open time, to, was 5.9 +/- 1.0 ms for NMDA and 5.3 +/- 1.7 ms for L-glutamate. The mean burst duration, tb, was 10.5 +/- 0.7 ms for NMDA and 8.5 +/- 2.0 ms for L-glutamate. 7. When the temperature was increased between 14 and 24 degrees C, the NMDA channel conductance increased with a Q10 of 1.6 while the mean open time decreased with a Q10 close to 2. 8. The NMDA channel showed, in addition to the 'main' conductance state (40-50 pS), smaller conductance states of 15 and 35 pS.(ABSTRACT TRUNCATED AT 400 WORDS)
The Journal of Physiology 06/1988; 399:207-26. · 4.72 Impact Factor
