Showing papers on "Kainate receptor published in 1986"

The anticonvulsant MK-801 is a potent N-methyl-D-aspartate antagonist.

Abstract: The compound MK-801 [(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d] cyclohepten-5,10-imine maleate)] is a potent anticonvulsant that is active after oral administration and whose mechanism of action is unknown. We have detected high-affinity (Kd = 37.2 +/- 2.7 nM) binding sites for [3H]MK-801 in rat brain membranes. These sites are heat-labile, stereoselective, and regionally specific, with the hippocampus showing the highest density of sites, followed by cerebral cortex, corpus striatum, and medulla-pons. There was no detectable binding in the cerebellum. MK-801 binding sites exhibited a novel pharmacological profile, since none of the major neurotransmitter candidates were active at these sites. The only compounds that were able to compete for [3H]MK-801 binding sites were substances known to block the responses of excitatory amino acids mediated by the N-methyl-D-aspartate (N-Me-D-Asp) receptor subtype. These comprised the dissociative anesthetics phencyclidine and ketamine and the sigma-type opioid N-allylnormetazocine (SKF 10,047). Neurophysiological studies in vitro, using a rat cortical-slice preparation, demonstrated a potent, selective, and noncompetitive antagonistic action of MK-801 on depolarizing responses to N-Me-D-Asp but not to kainate or quisqualate. The potencies of phencyclidine, ketamine, SKF 10,047, and the enantiomers of MK-801 as N-Me-D-Asp antagonists correlated closely (r = 0.99) with their potencies as inhibitors of [3H]MK-801 binding. This suggests that the MK-801 binding sites are associated with N-Me-D-Asp receptors and provides an explanation for the mechanism of action of MK-801 as an anticonvulsant.

Coupling of inositol phospholipid metabolism with excitatory amino acid recognition sites in rat hippocampus.

Abstract: Ibotenate, a rigid structural analogue of glutamate, markedly enhances the hydrolysis of membrane inositol phospholipids, as reflected by the stimulation of [3H]inositol monophosphate formation in rat hippocampal slices prelabeled with [3H]inositol and treated with Li+. Quisqualate, homocysteate, L-glutamate, and L-aspartate also induce a significant (albeit weaker) increase in [3H]inositol monophosphate formation, whereas N-methyl-D-aspartate, kainate, quinolinate, and N-acetylaspartylglutamate are inactive. The increase in [3H]inositol monophosphate formation elicited by the above-mentioned excitatory amino acids is potently and selectively antagonized by DL-2-amino-4-phosphonobutyric acid, a dicarboxylic amino acid receptor antagonist. These results suggest that, in the hippocampus, a class of dicarboxylic amino acid recognition sites is coupled with phospholipase C, the enzyme that catalyzes the hydrolysis of membrane inositol phospholipids.

Primary culture of identified neurons from the visual cortex of postnatal rats

Abstract: We have examined the properties of neurons from the visual cortex of postnatal Long Evans rats in dissociated cell culture. Visual cortex from rat pups 1–15 d old was subjected to enzymatic and mechanical dissociation to yield a suspension of single cells. Neurons plated onto collagen or a feeder layer of astrocytes rapidly extended processes and survived for 4–10 weeks. Antisera to glutamic acid decarboxylase, choline acetyltransferase, and vasoactive intestinal polypeptide stained 22 +/- 2, 2.3 +/- 0.3, and 2.4 +/- 0.2% of all neurons, respectively, suggesting that different neuronal classes survived roughly in proportion to their number in vivo. In order to study a particular identified class of cortical neurons, we prelabeled cells in vivo by retrograde transport of a fluorescent tracer. Neurons in layer V of visual cortex that project to the superior colliculus were labeled after injecting fluorescent latex microspheres into the colliculus. Retrogradely labeled neurons were readily identified immediately after dissociation and throughout the period in vitro. After 2 weeks in culture, labeled cells exhibited many ultrastructural features characteristic of pyramidal neurons in vivo. Intracellular recording techniques were used to evaluate the response properties of labeled layer V neurons, as well as other, unlabeled neurons, to excitatory amino acid agonists and antagonists. Glutamate and aspartate--as well as the synthetic agonists N-methyl-D-aspartate (NMDA), kainate, and quisqualate--excited every cortical neuron tested. The antagonist 2- amino-5-phosphonovaleric acid had no effect on responses to quisqualate and kainate but completely blocked depolarizations due to NMDA and aspartate and reduced depolarizations elicited by low concentrations of glutamate. Kynurenic acid, piperidine dicarboxylic acid, and gamma-D- glutamylglycine antagonized responses to all 5 of the agonists. These results provide evidence that corticocollicular neurons in culture express both NMDA-type and non-NMDA receptors for excitatory amino acids.

Frequency-dependent involvement of NMDA receptors in the hippocampus: a novel synaptic mechanism

Abstract: Acidic amino acids, such as l-glutamate, are believed to be excitatory neurotransmitters in the mammalian brain and exert effects on several different receptors named after the selective agonists kainate, quisqualate and N-methyl-D-aspartate (NMDA). The first two receptors collectively termed non-NMDA receptors, have been implicated in the mediation of synaptic transmission in many excitatory pathways in the central nervous system (CNS), whereas NMDA receptors, with few exceptions do not appear to be involved; this is typified in the hippocampus where there is a high density of NMDA receptors yet selective NMDA receptor antagonists, such as D-2-amino-5-phosphonovalerate (APV), do not affect synaptic potentials. NMDA receptors have, however, been shown to be involved in long-term potentiation (LTP) in the hippocampus, a form of synaptic plasticity which may be involved in learning and memory. NMDA receptors have also been found to contribute to epileptiform activity in this region. We now describe how NMDA receptors can participate during high-frequency synaptic transmission in the hippocampus, their involvement during low-frequency transmission being greatly suppressed by Mg2+. A frequency dependent alleviation of this blockade provides a novel synaptic mechanism whereby a single neurotransmitter can transmit very different information depending on the temporal nature of the input. This mechanism could account for the involvement of NMDA receptors in the initiation of LPT and their contribution, in part, to epileptic activity.

Neurons containing NADPH-diaphorase are selectively resistant to quinolinate toxicity.

Abstract: Exposure of cultures of cortical cells from mouse to either of the endogenous excitatory neurotoxins quinolinate or glutamate resulted in widespread neuronal destruction; but only in the cultures exposed to quinolinate, an N-methyl-D-aspartate agonist, was there a striking preservation of the subpopulation of neurons containing the enzyme nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d). Further investigation revealed that neurons containing NADPH-d were also resistant to the toxicity of N-methyl-D-aspartate itself but were selectively vulnerable to the toxicity of either kainate or quisqualate. Thus, neurons containing NADPH-d may have an unusual distribution of receptors for excitatory amino acids, with a relative lack of N-methyl-D-aspartate receptors and a relative preponderance of kainate or quisqualate receptors. Since selective sparing of neurons containing NADPH-d is a hallmark of Huntington's disease, the results support the hypothesis that the disease may be caused by excess exposure to quinolinate or some other endogenous N-methyl-D-aspartate agonist.

The primary afferent depolarizing action of kainate in the rat

Abstract: Dorsal roots (L3-L7) isolated from immature (1-9 day old) rats were depolarized selectively by kainate (1-100 microM). L-Glutamate (25-100 microM), but not L-aspartate, mimicked the action of kainate. N-methylaspartate had no activity on these preparations and quisqualate was thirty times less active than kainate. Depolarizations evoked by L-glutamate (100-1000 microM) faded rapidly in the presence of L-glutamate. Depolarizations evoked by kainate were depressed during the fade induced by L-glutamate. Certain electrically evoked C-fibre volleys in dorsal roots or leg nerves of rats at any age were selectively depressed or abolished in the presence of kainate. The effect of kainate was more selective than that of gamma-aminobutyric acid or capsaicin. Prolonged treatment of dorsal roots with kainate did not appear to be deleterious to C-fibres. It is suggested that certain primary afferent C-fibres possess kainate receptors which may be activated physiologically by L-glutamate released at their central terminations.

Characterization of the inhibition of excitatory amino acid-induced neurotransmitter release in the rat striatum by phencyclidine-like drugs.

Abstract: In the present study, the authors found that, in Mg++-free buffer, N-methyl-D-aspartate (NMDA) was able to evoke the Ca++-dependent and tetrodotoxin-sensitive release of striatal acetylcholine (ACh), presumably via interaction with receptors on cholinergic interneurons. In Mg++-free buffer containing pargyline, NMDA also evoked a Ca++-dependent and tetrodotoxin-sensitive release of striatal [3H]dopamine (DA). Phencyclidine (PCP) and physiological concentrations of Mg++ (1.2 mM) also inhibited ACh release evoked by L-glutamate, L-aspartate and DL-homocysteate, but not ACh release evoked by the glutamate analogs quisqualate and kainate, suggesting that PCP is selective for the magnesium-sensitive, NMDA-preferring glutamate-aspartate receptor subtype. Comparison of PCP inhibition of NMDA-stimulated ACh and DA release with that produced by the competitive NMDA antagonist 2-amino-5-phosphonovalerate indicates that PCP is probably not altering release by a direct action on the NMDA recognition site. The ability of 2-amino-5-phosphonovalerate, but not PCP, to prevent desensitization of NMDA-induced ACh release is consistent with this interpretation. Binding studies did, however, reveal a reduction in the apparent affinity of the PCP binding site by high concentrations of NMDA. This may suggest an allosteric link between the PCP-sigma receptor and the NMDA-type glutamate-aspartate receptor. The receptors mediating excitatory amino acid-induced DA release were somewhat less selective than those on cholinergic neurons in their sensitivity to both Mg++ and PCP. Structure-activity-relationship studies suggested that the inhibition off ACh and DA release evoked by NMDA involves biding to the PCP-sigma receptor.(ABSTRACT TRUNCATED AT 250 WORDS)

Mediation of thalamic sensory input by both NMDA receptors and non-NMDA receptors.

Abstract: Excitatory amino acids such as L-glutamate and L-aspartate are well established as neurotransmitter candidates in the mammalian central nervous system, and three types of receptor for these substances have been proposed, characterized by the agonists N-methyl-D-aspartate (NMDA), kainate and quisqualate. All these receptors have been suggested to have synaptic roles in excitatory transmission in the brain. Here I demonstrate that NMDA receptors play a crucial role in the observed response of ventrobasal thalamus (VB) neurones to natural stimulation of somatosensory afferents, but do not appear to be responsible for the short-latency excitation seen on electrical stimulation of the afferents which is apparently mediated by excitatory amino-acid receptors of the non-NMDA type. This result indicates an involvement of NMDA and non-NMDA receptors in the responses of VB neurones to stimulation of somatosensory somatosensory afferents, depending on the mode of stimulation of the pathway.

Kynurenic acid and quinolinic acid act at N-methyl-D-aspartate receptors in the rat hippocampus.

Abstract: Responses evoked by several amino acid excitants, including the tryptophan metabolite quinolinic acid, were recorded intracellularly from CA1 pyramidal neurons in rat hippocampal slices. Quinolinate, N-methyl-D-aspartate (NMDA), ibotenate and (+/-)-cis-1-amino-1,3-dicarboxycyclopentane produced excitations characterized by burst firing of action potentials, tetrodotoxin-resistant spiking and apparent increases in input resistance measured with brief hyperpolarizing current pulses. L-Glutamate, kainate, quisqualate and (+/-)-2'-amino-3-hydroxy-5-methyl-4-isoxazole-3'-propionate depolarized CA1 pyramidal neurons and induced apparent decreases in input resistance. Quinolinate-, NMDA-, and ibotenate-induced focal depolarizations, but not L-glutamate, kainate- or quisqualate-induced responses, were strongly antagonized by specific NMDA receptor antagonists. The tryptophan metabolite kynurenic acid, at concentrations that antagonized focal depolarizations produced by NMDA, ibotenate and the endogenous excitant quinolinate, did not antagonize quisqualate or L-glutamate responses. In addition to its NMDA-type antagonist action, kynurenate blocked kainate-induced focal depolarizations.

Characterization of excitatory amino acid receptors expressed by embryonic chick motoneurons in vitro.

Abstract: We have examined the effect of L-glutamate and other excitatory amino acids on embryonic chick motoneurons maintained in cell culture along with other types of spinal cord cells. When the motoneuron membrane is clamped at -50 mV, glutamate induces a dose-dependent inward current. Although the dose-response curve is hyperbolic with an ED50 of 78 microM, glutamate apparently activates 2 types of receptors on motoneurons. The first, G1, is activated by N-methyl-D-aspartate (NMDA) and aspartate and inhibited by 2-amino-5-phosphonovaleric acid (2-APV). The second, G2, is activated by kainate and quisqualate and is not inhibited by 2-APV. At -50 mV, 38% of the glutamate current is due to activation of G1 receptors and the remaining 62% to G2 activation. In contrast to motoneurons grown with other spinal cord cells, sorted motoneurons grown in isolation apparently exhibit only G2 receptor- mediated currents. Both G1 and G2 currents reverse polarity between -10 and -5 mV. However, they could be distinguished when the membrane was hyperpolarized. G2 currents increased but G1 currents decreased when the membrane potential was increased beyond -50 mV. Consistent with the mixed agonist action of glutamate, glutamate currents remained nearly constant on hyperpolarization. No evidence was obtained that the G2 class of receptors on motoneurons could be subdivided: Quisqualate and kainate apparently compete for the same sites; gamma-glutamylglycine blocked quisqualate as effectively as it blocked kainate currents when the different potencies of the 2 agonists were taken into account.(ABSTRACT TRUNCATED AT 250 WORDS)

Dual-component synaptic potentials in the lamprey mediated by excitatory amino acid receptors

Abstract: The synaptic mechanisms underlying amino acid-mediated excitation in the lamprey spinal cord have been investigated. Fine stimulating electrodes were used to stimulate single axons in the spinal cord and evoke unitary EPSPs in lamprey motoneurons and one type of premotor interneuron, the CC interneuron. Three types of EPSP, distinguished by their time course and sensitivity to amino acid antagonists, were seen. Fast EPSPs had a fast rise time (mean, 6.5 msec) and a short half-decay time (mean, 22.5 msec). Slow EPSPs lasted at least 200 msec, had a slow rise time (mean, 28 msec), and a long half-decay time (mean, 109 msec). The third type of unitary potential, called “mixed” EPSP, also lasted at least 200 msec, had a fast rise time (mean, 12 msec), and a long half-decay time (mean, 105 msec). Lamprey neurons were found to possess 3 types of excitatory amino acid receptor: N-methyl-D-aspartate (NMDA), kainate, and quisqualate receptors. 2-Amino-5-phosphonovaleric acid (APV) or Mg2+ blocked the depolarizations caused by N-methyl-D,L- aspartate (NMA) but not those of kainate or quisqualate. Cis-2, 3- piperidine dicarboxylic acid (PDA) blocked the depolarizations caused by NMA and kainate but not those of quisqualate. Fast EPSPs were unaffected by the bath application of APV or Mg2+ but were greatly reduced by PDA, suggesting that these EPSPs were mediated by non-NMDA, possibly kainate receptors. Both APV and Mg2+ blocked the slow EPSPs, suggesting that they were mediated by NMDA receptors.

Modulation of embryonic chick motoneuron glutamate sensitivity by interneurons and agonists

Abstract: Embryonic chick motoneurons grown in culture together with other spinal cord cells are more sensitive to L-glutamate than are sorted motoneurons grown in isolation. After 6 d in vitro, the difference in peak sensitivity reached 6-fold. Comparable increases in aspartate and kainate currents were observed, indicating that both G1 and G2 amino acid receptors were affected. Elimination of proliferating non-neuronal cells from mixed spinal cord cell cultures by addition of cytosine arabinoside (ara C) did not prevent the increase in motoneuron chemosensitivity, so the induction is probably due to the presence of interneurons. In contrast to their effect on glutamate response, interneurons did not affect the sensitivity of motoneurons to the inhibitory neurotransmitters GABA and glycine. Glutamate receptors expressed by sorted and unsorted motoneurons are identical in terms of their ED50, reversal potential, mean channel open time, and conductance, implying that the increased sensitivity of motoneurons in mixed cultures is due to an increase in the number of open channels. In addition to an increase in the number of channels, the distribution of glutamate sensitivity over the surface of individual motoneurons was altered in interneuron-containing cultures. The sensitivity of isolated motoneurons was greatest at the soma and decreased with distance along major processes, but the sites of highest sensitivity on motoneurons in mixed cultures occurred along their processes. Sharp peaks identified by focal iontophoresis of glutamate were separated by areas of lower sensitivity. The inductive effect of interneurons cannot be due to glutamate, the most likely excitatory interneuron-motoneuron transmitter in 6 d chick cultures.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino acid receptor-mediated transmission at primary afferent synapses in rat spinal cord

Abstract: Intracellular recording techniques have been used to provide information on the identity of excitatory transmitters released at synapses formed between dorsal root ganglion (DRG) and spinal cord neurones in two in vitro preparations. Explants of embryonic rat DRG were added to dissociated cultures of embryonic dorsal horn neurones and synaptic potentials recorded intracellularly from dorsal horn neurones after DRG explant stimulation. More than 80% of dorsal horn neurones received at least one fast, DRG-evoked, monosynaptic input. In the presence of high divalent cation concentrations (5 mmol l-1 Ca2+, 3 mmol l-1 Mg2+) the acidic amino acid receptor agonists, L-glutamate, kainate (KA) and quisqualate (QUIS) excited all dorsal horn neurones which received a monosynaptic DRG neurone input, whereas L-aspartate and N-methyl-D-aspartate (NMDA) had little or no action. 2-Amino-5-phosphonovalerate (APV), a selective NMDA receptor antagonist, was relatively ineffective at antagonizing DRG-evoked synaptic potentials and L-glutamate-evoked responses. In contrast, kynurenate was found to be a potent antagonist of amino acid-evoked responses and of synaptic transmission at all DRG-dorsal horn synapses examined. The blockade of synaptic transmission by kynurenate appeared to result from a postsynaptic action on dorsal horn neurones. Intracellular recordings from motoneurones in new-born rat spinal cord were used to study the sensitivity of the Ia excitatory postsynaptic potential (EPSP) to antagonists of excitatory amino acids. Superfusion of the spinal cord with APV did not inhibit the Ia EPSP but did suppress later, polysynaptic components of the afferent-evoked response. Kynurenate was a potent and selective inhibitor of the Ia EPSP, acting via a postsynaptic mechanism. These findings indicate that L-glutamate, or a glutamate-like compound, but not L-aspartate, is likely to be the predominant excitatory transmitter that mediates fast excitatory postsynaptic potentials at primary afferent synapses with both dorsal horn neurones and motoneurones.

Excitatory amino acid transmitters in neuronal circuits of the cat visual cortex.

Abstract: To test a possibility that glutamate (Glu) and aspartate (Asp) are transmitters in the visual cortex and to locate their operating sites in the cortical circuitry, we studied effects of microiontophoretic application of Glu/Asp antagonists on visual responses of cortical neurons in the cat. The antagonists tested were kynurenic acid (KYNA), cis-2,3-piperidine dicarboxylic acid, and gamma-D-glutamylglycine. Among these antagonists, KYNA was most effective in blocking visual responses of cortical neurons; it eliminated visual responses in 156 of the 188 cells tested. Usually the maximal suppressive effect appeared 20-30 s after starting KYNA application and recovery of cell's responsiveness 30-60 s after stopping the application. KYNA antagonized excitations induced by ionophoretic application of Glu and Asp but did not block those by acetylcholine, suggesting that KYNA is a selective antagonist of Glu/Asp, and its action is not due to general depressant effects. This suggestion was further supported by the observation that in corticogeniculate cells the latency and probability of invasion of antidromic spikes into the somatodendritic part following electrical stimulation of the lateral geniculate were not changed while visual responses were completely suppressed by KYNA. In terms of actions of the three agonists which give the basis for classifying excitatory amino acid receptors into at least three types, KYNA antagonized excitations by N-methyl-D-aspartic acid (NMDA) and kainate in almost all the cells tested but did not block those by quisqualate in about half of the cells. These results suggest that KYNA reacts more preferentially with NMDA and kainate receptors than with quisqualate receptors. Effectiveness of KYNA was related to types of receptive fields of cells and to their laminar locations. In 79 of the 104 simple cells tested, KYNA completely suppressed their visual responses, while such a complete block was seen in only 18 of the 68 complex and 3 of the 16 special complex cells. The great majority of the cells in layers IVab, IVc and the upper part of layer VI were completely suppressed by KYNA, whereas most of the cells in the other layers were incompletely suppressed or not suppressed at all.(ABSTRACT TRUNCATED AT 400 WORDS)

Excitatory Amino Acids and Epilepsy

Abstract: Session I. The Limbic System: Neuroanatomical Concepts Relating to Epileptic Phenomena.- Amygdalohippocampal and Amygdalocortical Projections in the Primate Brain.- Subcortical Projections from the Amygdaloid Complex.- Cortical and Subcortical Afferents of the Amygdaloid Complex.- Putative Amino Acid Transmitters in the Amygdala.- A Survey of the Anatomy of the Hippocampal Formation, With Emphasis on the Septotemporal Organization of its Intrinsic and Extrinsic Connections.- Cytochemical Architecture of the Entorhinal Area.- Session I: Commentary.- Session II. Epileptic Brain Tissue: Neuropathology and Physiology in Animals and Man.- Neuronal and Glial Pathologies: Morphology and Physiology of Human and Monkey Epileptic Foci.- Metabolic, Morphologic and Electrophysiologic Profiles of Human Temporal Lobe Foci: An Attempt at Correlation.- Endogenous Excitotoxins as Possible Mediators of Ischemic and Hypoglycemic Brain Damage.- Role of the Substantia Nigra in the Kindling Model of Limbic Epilepsy.- Long Term Sequelae of Parenteral Administration of Kainic Acid.- Electrophysiology of Epileptic Tissue: What Pathologies are Epileptogenic?.- Session III. Excitatory Amino Acids and the Blood-Brain Barrier.- Pathophysiological Aspects of Blood-Brain Barrier Permeability in Epileptic Seizures.- Blood-Brain Barrier Permeability to Excitatory Amino Acids.- Limbic Seizures Induced by Systemically Applied Kainic Acid: How Much Kainic Acid Reaches the Brain?.- Extravasated Protein as a Cause of Limbic Seizure-Induced Brain Damage: An Evaluation Using Kainic Acid.- Ultrastructural Analysis of Rat Brain Tissue Following Systemic Kainate Administration.- Session III: Commentary.- Session IV. Excitatory Amino Acids: Receptor Interactions.- Anatomical Organization of Excitatory Amino Acid Receptors and their Properties.- Homocysteic Acid, an Endogenous Agonist of NMDA-Receptor: Release, Neuroactivity, and Localization.- Excitatory Amino Acid Pathways in the Brain.- Synthesis and Release of Amino Acid Transmitters.- Na+ Fluxes as a Tool to Identify Anticonvulsant Antagonists of Neuroexcitation.- Involvement of Excitatory Amino Acid Receptors in the Mechanisms Underlying Excitotoxic Phenomena.- Session IV: Commentary.- Session V. Excitatory Amino Acids and Seizures: Neurochemical Interrelationships.- Excitatory Amino Acid Antagonists as Novel Anticonvulsants.- The Hyperexcited Brain: Glutamic Acid Release and Failure of Inhibition.- Anti.-Excitotoxic Actions of Taurine in the Rat Hippocampus Studied In Vivo and In Vitro.- Alterations in Extracellular Amino Acids and Ca2+ Following Excitotoxin Administration and During Status Epilepticus.- Acidic Peptides in Brain: Do They Act at Putative Glutamatergic Synapses?.- Session V: Commentary.- Session VI. Mechanisms of Epileptogenesis.- Synaptic Events Underlying Spontaneous and Evoked Paroxysmal Discharges in Hippocampal Neurons.- Inward Currents in Cat Neocortical Neurons Studied In Vitro.- Synchronization of Pyramidal Cell Firing by Ephaptic Currents in Hippocampus In Situ.- Excitatory Amino Acids and Regenerative Activity in Cultured Neurons.- Long-Term Alterations in Amino Acid-Induced Ionic Conductances in Chronic Epilepsy.- Excitatory Amino Acids and Epilepsy-Induced Changes in Extracellular Space Size.- Session VI: Commentary.- Session VII. Excitatory Amino Acids: Physiological Studies.- Evidence for the Activation of the N-Methyl-D-Aspartate Receptor During Epileptiform Discharge.- Effects of Kainate on CA1 Hippocampal Neurons Recorded In Vitro.- Blockade by D-Aminophosphonovalerate or Mg2+ of Excitatory Amino Acid-Induced Responses on Spinal Motoneurons In Vitro.- The Membrane Action of Excitatory Amino Acids on Cultured Mouse Spinal Cord Neurons.- A Patch-Clamp Study of Excitatory Amino Acid Activated Channels.- Amino Acid Activated Receptor-Channels at Peripheral and Central Synapses.- Expression of Vertebrate Amino Acid Receptors in Xenopus Oocytes.- Session VII: Commentary.- Session VIII. Metal Ions and Epilepsy.- Transition Metal Ions in Epilepsy: An Overview.- Zinc-Binding Proteins in the Brain.- Neurobehavioral, Neuroendocrine and Neurochemical Effects of Zinc Supplementation in Rats.- Excitatory Amino Acids and Divalent Cations in the Kindling Model of Epilepsy.- Effect of Zinc on Neuronal Activity in the Rat Forebrain.- Relationship of Glutamic Acid and Zinc to Kindling of the Rat Amygdala: Afferent Transmitter Systems and Excitability in a Model of Epilepsy.- Session VIII: Commentary.- Session IX. Seizures and Brain Damage: The Excitotoxic Link.- Inciting Excitotoxic Cytocide Among Central Neurons.- Selective and Non-selective Seizure Related Brain Damage Produced by Kainic Acid.- On the Role of Seizure Activity and Endogenous Excitatory Amino Acids in Mediating Seizure-Associated Hippocampal Damage.- Kainic Acid Seizures and Neuronal Cell Death: Insights from Studies of Selective Lesions and Drugs.- Glutamate and Anoxic Neuronal Death In Vitro.- Quinolinic Acid: A Pathogen in Seizure Disorders?.- Session IX: Commentary.- Contributors.

Anatomical Organization of Excitatory Amino Acid Receptors and Their Properties

Abstract: The excitatory amino acids are the major class of excitatory neurotransmitter in the CNS and their actions are mediated by four or more physiologically-identified receptor classes. Electrophysiological experiments indicate that L-glutamate excitations are mediated by at least three agonistdefined receptors (N-methyl-D-aspartate (NMDA), kainate, (KA), and quisqualate(QA); Watkins and Evans, 1981; Cotman et al., 1981; McLennan, 1981).And a fourth class characterized by the antagonism of synaptic responses by L-2-amino-4-phosphonobutyric acid (L-AP4; Koerner and Cotman, 1981). In order to understand the role of these receptors in the operation of brain circuitry, several approaches are needed, all of which must ultimately be in accord. Electrophysiological studies are required to assess the functional properties and membrane conductance events, and biochemical studies are needed to characterize the detailed receptor properties and assess their regulation. These approaches have traditionally been used in studying the physiology and pharmacology of many receptors throughout the body. However, the CNS is extremely heterogeneous and multiple receptors exist in specific regions which may have different properties. Thus,in addition to traditional approaches, it is desirable to have a method which allows the direct visualization and study of biochemical properties of receptor classes in discrete brain areas. Autoradiography can be used for this purpose. We have found that when great attention is paid toward resolving the multiple receptor populations, the pharmacological properties in autoradiography closely parallel those obtained by neurophysiological analysis in the same receptor field. Until our recent studies, this was not clear and several contradictions existed. Many of these inconsistencies have now been resolved.