Kainate, N-methylaspartate and other excitatory amino acids increase calcium influx into rat brain cortex cells in vitro

Berdichevsky, Elisa; Riveros, Nora; Sánchez‐Armass, Sergio; Orrego, Fernando

doi:10.1016/0304-3940(83)90489-5

Cited by 147 publications

(55 citation statements)

References 27 publications

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“…Rothman (1983Rothman ( ,1984 revealed that hippocampal neuron cultures deteriorated in the absence of oxygen but such cultures tolerated prolonged anoxia when synaptic activity was blocked by elevated Mg' -+ , suggesting a role for the synaptic release of excitatory neurotransmitters, most likely glutamate and/or aspartate, in the mediation of anoxic neuronal injury. Surprisingly, the excitatory amino acids were neurotoxic in medium that contained no added Ca t , in agreement with observations of Price et al (1985), casting doubt on the hypothesis that Ca t entry was responsible for the neuronal death (Berdichevsky et al, 1983;Coyle, 1983). The maintenance of cytosolic Ca t at a physiological level depends on energy-dependent transport systems and it is expected that hypoxic, anoxic, or ischemic conditions known to deplete intracellular ATP would likely cause a disruption of Ca t homeostasis (Brattin et al, 1984;Jewell et al, 1982;Johnson et al, 1987;Nicotera et al, 1989).…”

Section: Introductionsupporting

confidence: 74%

Paradoxical potentiation by low extracellular Ca2+ of acute chemical anoxic neuronal injury in cerebellar granule cell culture

Verity

Torres

Sarafian

1991

Molecular and Chemical Neuropathology

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Acute chemical anoxic injury was produced in primary cerebellar granule cell cultures incubated with iodoacetate (IAA) alone or IAA combined with potassium cyanide (KCN). Cytotoxicity was assessed using Trypan blue exclusion or LDH release. Four millimolars of KCN induced approx 30% neuron death at 3 h, whereas >50% cell death was produced by 0.2 mM IAA. No potentiation of cytotoxicity was observed by IAA + KCN. A total of 0.2 mM IAA produced an early major reduction of intracellular ATP prior to the onset of neuron injury or reduction in intracellular glutathione (GSH). Medium Na + replacement by choline, K + , or methylglucamine protected against IAA-induced neuronal injury, reduced the rate of decline of intracellular ATP but had no effect on intracellular GSH. Some 80% neuronal survival was obtained when Na + was deleted from the medium even after the intracellular ATP had been reduced to <10% of control. Removal of Cat from the medium had no effect on control culture, Trypan blue exclusion, GSH, or ATP, but potentiated the onset and magnitude of IAA-induced cytotoxicity, ATP and GSH decline. Loading of granule cells with the Cat chelator Fura-2 did not influence *Author to whom all correspondence and reprint requests should be addressed. Molecular and Chemical Neuropathology 217Vol. 15, 1991 218 Verity, Torres, and Sarafian IAA-induced cytotoxicity in control or low Cat media. Addition of 50 µM glutamate had a minimal cytotoxic effect over 3 h and the combined addition of 0.2 mM IAA plus 50 µM glutamate did not potentiate IAA-induced injury. The glutamate receptor antagonists, D-2-amino -5-phosphonovaleric acid (APV) or kynurenate did not block IAA-injuced injury in control medium but inhibited the potentiation of toxicity seen in the low Ca t medium.This study suggests the use of IAA as a chemical anoxic agent in cerebellar granule cell culture. The early, dose-dependent decline in ATP may be dissociated from GSH change. Acute IAA-induced injury is Na/Cl -dependent but paradoxically potentiated in low Ca t+ medium. The low Cat potentiated component was sensitive to glutamate/NMDA receptor antagonists and associated with reduction of intracellular GSH.

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Section: Introductionsupporting

confidence: 74%

Paradoxical potentiation by low extracellular Ca2+ of acute chemical anoxic neuronal injury in cerebellar granule cell culture

Verity

Torres

Sarafian

1991

Molecular and Chemical Neuropathology

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“…Cellular mechanism of glutamate action Several lines of evidence have implicated calcium as a mediator of the effects of neurotransmitters and electrical activity on neuronal outgrowth (Cohan et al, 1987;Mattson andKater, 1987, Mattson et al, 1987) and survival (Coyle et al, 198 1;Berdichevsky et al, 1983;Coyle et al, 1981;Donaldson et al, 1983;Mayer and Westbrook, 1987). Studies in invertebrate central neurons demonstrated that serotonin and electrical activity can suppress neurite outgrowth by causing calcium influx (Cohan et al, 1987;Mattson and Kater, 1987).…”

Section: Discussionmentioning

confidence: 99%

“…One proposed cellular mechanism whereby EAAs exert their toxic effects is by depolarizationinduced calcium influx (Coyle et al, 198 1;Berdichevsky et al, 1983;Mayer and Westbrook, 1987). In order to test the possibility that depolarization-induced calcium influx was involved in the graded effects of EAAs on pyramidal cell outgrowth and survival, we employed agents known for their negative or positive effects on calcium influx as well as elevated extracellular K+.…”

Section: Glutamate Receptors Afecting Neuronal Outgrowth and Survivalmentioning

confidence: 99%

Outgrowth-regulating actions of glutamate in isolated hippocampal pyramidal neurons

1988

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The present study examined the effects of glutamate on the outgrowth of dendrites and axons in isolated hippocampal pyramidal-like neurons in cell culture. During the first day of culture the survival and outgrowth of these neurons was unaffected by high concentrations (up to 1 nM) of glutamate, quisqualic acid (QA), kainic acid (KA), and N- methyl-D-aspartic acid. Beginning on day 2 of culture high levels of glutamate, KA and QA were toxic to the majority of pyramidal neurons, while subtoxic levels of these agents caused a well-defined, dose- dependent, sequence of effects on dendritic outgrowth. At increasing concentrations of glutamate, QA, and KA, the following events were observed: (1) dendritic outgrowth rates were reduced, while axonal elongation rates were unaffected; (2) dendritic length was reduced, while axons continued to grow; (3) dendrites regressed dramatically, and axonal outgrowth rate was reduced. These dendrite-specific effects of glutamate were apparently mediated at the growth cones since focal application of glutamate to individual dendritic growth cones resulted in suppression of growth cone activity and a regression of the dendrite; axons were unaffected by focal glutamate application. Pharmacological tests using glutamate receptor agonists and antagonists demonstrated that receptors of the KA/QA type mediated the glutamate effects on outgrowth and survival. The calcium channel blocker Co2+ prevented both glutamate neurotoxicity and glutamate-induced dendritic regression. Ionophore A23187 and elevations in extracellular K+ levels each caused a dose-dependent series of outgrowth and survival responses similar to those caused by glutamate. Taken together, these results indicate that activation of glutamate receptors leads to the opening of voltage-dependent calcium channels; the resulting increases in calcium influx lead to the observed alterations in dendritic outgrowth and neuronal survival.

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“…Many neurophysiological studies carried out during the past few years have suggested mechanisms of kainate toxicity in the brain. It has commonly been proposed that the toxicity of kainate is due to tissue hypoxia resulting from an induced hyperactivity of the neurons [3-51. Consistent with this hypothesis are biochemical studies (particularly on brain slices), which showed that kainate caused increase in intracellular contents of water and sodium [6], influx of 45Ca2+ and **Na+ into the inulin-impermeant space [7], release of aspartate and glutamate and increase of extracellular potassium [12]. On the other hand, results of Pinard and co-workers [13] provide evidence that hypoxia cannot be considered re-* On leave from the Laboratory of Neurochemistry, Experimental and Clinical Medical Research Center, 3 Dworkowa St, 00-784, Warsaw, Poland + To whom correspondence should be addressed sponsible for the damage produced by kainate.…”

Section: Introductionmentioning

confidence: 68%

Kainate‐induced uptake of calcium by synaptosomes from rat brain

Pastuszko

Wilson

1985

FEBS Letters

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Kainic acid induces a rapid increase in 45Ca2+ uptake by crude synaptosomal fractions isolated from rat brain. This enhanced Ca*+ permeability occurs with a half-time of approx. 1 s, similar to the fast phase of depolarization-induced calcium uptake. The depolarization-induced uptake of calcium is inhibited 85% by 3 mM CoCl,, 80% by 100 PM quinacrine and 50% by 15 PM trifluoperazine while these agents had little effect on the kainate-induced uptake. It is proposed that kainate induces receptor-mediated opening of a class of calcium channels with properties different from those of the voltage-dependent channels. Kainic acid Calcium uptake Synuptosome

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Kainate, N-methylaspartate and other excitatory amino acids increase calcium influx into rat brain cortex cells in vitro

Cited by 147 publications

References 27 publications

Paradoxical potentiation by low extracellular Ca2+ of acute chemical anoxic neuronal injury in cerebellar granule cell culture

Paradoxical potentiation by low extracellular Ca2+ of acute chemical anoxic neuronal injury in cerebellar granule cell culture

Outgrowth-regulating actions of glutamate in isolated hippocampal pyramidal neurons

Kainate‐induced uptake of calcium by synaptosomes from rat brain

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