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L Fagni

Publications and source records attributed to L Fagni.

53 records · Page 3Linked to original sources
PubMed1989

Charybdotoxin blocks dendrotoxin-sensitive voltage-activated K+ channels.

Charybdotoxin, a short scorpion venom neurotoxin, which was thought to be specific for the blockade of Ca2+-activated K+ channels also blocks a class of voltage-sensitive K+ channels that are known to be the target of other peptide neurotoxins from snake and bee venoms such as dendrotoxin and MCD peptide. Charybdotoxin also inhibits 125I-dendrotoxin and 125I-MCD peptide binding to their receptors. All these effects are observed with an IC50 of about 30 nM.

Animals↗
PubMed1989

Voltage-activated calcium channels in rat Purkinje cells maintained in culture.

Cell-attached patch recordings were used to study calcium channels on the dendritic membrane of rat cerebellar Purkinje cells maintained in culture. Experiments were performed with isotonic BaCl2 (110 mM) in the pipette and isotonic potassium gluconate in the bath to zero the cell membrane potential. Two distinct types of voltage-activated calcium channels were identified. The first one had a small conductance (9 pS), was activated at a low threshold (congruent to -50 mV) and could be inactivated by holding the membrane potential at -30 mV. This channel had the same characteristics as the T channel described in other neuronal preparations. The second type of Ca channel activated at a high threshold (-30 or +10 mV depending on whether BAY K 8644 was added or not to the pipette solution) and was still activatable even when the membrane was held at -40 mV. In the presence of BAY K 8644 this channel had a conductance of 21 pS with long openings. All these characteristics are similar to those of the S (L) Ca channel described in many preparations. The present study is in agreement with our previous experiments on Purkinje dendrites, where we identified low and high threshold Ca currents using the whole-cell configuration. Up to now, no channel corresponding to the N current has been observed but we cannot exclude its presence.

Animals↗
PubMed1989

The action of hydrogen peroxide on paired pulse and long-term potentiation in the hippocampus.

The action of a reactive oxygen intermediate, that is, hydrogen peroxide (H2O2) on modulation of synaptic transmission was examined in the hippocampal brain slice preparation. Microinjection of H2O2 into the apical dendritic region of the CA1 pyramidal cells produced no change in either the pattern or amplitude of paired pulse facilitation compared to saline injection (control). Long term potentiation (LTP), induced by high frequency stimulation of homosynaptic inputs, however, was blocked by microinjection of H2O2 into the dendritic tree. LTP was seen in only 2 out of 10 slices investigated when treated with H2O2 while LTP was seen in 4 out of 5 slices when saline injected. The results suggest that a reactive oxygen intermediate can selectively modify synaptic mechanisms in the hippocampus.

Action Potentials↗
PubMed1988

Decrease of recurrent and feed-forward inhibitions under high pressure of helium in rat hippocampal slices.

The effect of high helium pressure on inhibitory synaptic transmission was studied in rat hippocampal slices with extracellular recordings. Both feed-forward and recurrent GABAergic inhibition were tested in the CA1 region with paired-pulse stimulation paradigms. The efficiency of both types of inhibition decreased under high pressure (80 atm). However, the depression of synaptic and antidromic field potentials induced by perfusion of GABA or muscimol were not significantly affected by pressure. High pressure induced hyperexcitability of CA1 pyramidal cells. This effect was reduced by the application of 2-aminophosphonovalerate or GABA. The present results suggest that: (1) high pressure reduces the efficiency of the GABAergic inhibitory transmission but does not affect the sensitivity of GABAA receptors; (2) two different processes (reduction of GABAergic inhibition and facilitation of N-methyl-D-aspartate-mediated excitation) might be a direct consequence of the change in the voltage-sensitive ion channels under high pressure and might be involved in the development of the pressure-induced hyperexcitability of CA1 pyramidal cells.

2-Amino-5-phosphonovalerate↗
PubMed1988

The influence of helium pressure on the reduction induced in field potentials by various amino acids and on the GABA-mediated inhibition in the CA1 region of hippocampal slices in the rat.

In a previous study, it was shown that helium pressure depressed excitatory synaptic transmission mediated by the Schaffer-commissural afferents and increased the intrinsic excitability of pyramidal cells, in the CA1 region of hippocampal slices in the rat. In the present study, the neurochemical bases of these changes was investigated. Various excitatory amino acids were studied under normal and up to 80 atm of helium. At normal pressure, the amino acids tested induced a decrease in the field excitatory postsynaptic potential (EPSP) and antidromic field potential of CA1 pyramidal cells. These changes probably resulted from the well known depolarizing effect of the compounds. Quisqualate is supposed to activate the synaptic receptors of the pathway tested. Since the effect of this amino acid and other agonists were not significantly affected by helium pressure, it is suggested that the depressed hippocampal synaptic potentials under pressure did not result from reduced sensitivity of synaptic receptors. On the other hand, helium pressure enhanced the action of N-methyl-D-aspartate (NMDA) and depressed the GABA-mediated inhibition of CA1 pyramidal cells. Given that the excitability of these neurones is modulated by NMDA-related events and GABA inhibition, these results indicate that both neurochemical systems were probably involved in the helium pressure-induced hyperexcitability of the cells studied.

Action Potentials↗
PubMed1987

Helium pressure potentiates the N-methyl-D-aspartate- and D,L-homocysteate-induced decreases of field potentials in the rat hippocampal slice preparation.

We examined the influence of helium pressure on the depression induced by various excitatory amino acids in CA1 hippocampal field potentials. The effects of quisqualate, L-glutamate, L-aspartate and kainate were not significantly affected by helium pressure, while those of N-methyl-D-aspartate and D,L-homocysteate were enhanced. These findings suggest that helium pressure specifically increased the sensitivity of the N-methyl-D-aspartate receptor type in the hippocampus. Other hypotheses are discussed.

Action Potentials↗
PubMed1987

Evoked potential changes in rat hippocampal slices under helium pressure.

High pressures of helium affect the physiology of the central nervous system in animals and humans. We examined these effects in rat hippocampal slices. The in vitro preparation displayed a reversible reduction in postsynaptic and antidromic field potentials of CA1 pyramidal cells, but no significant change in the amplitude of the afferent volley. Although the subliminal synaptic response of CA1 neurons was depressed, the ability of these cells to produce population spikes was enhanced. These changes resembled those previously found in vivo in the rat hippocampus. The present results support the hypothesis of a helium pressure-induced depolarization of hippocampal neurons. Other possible mechanisms are discussed.

Animals↗
PubMed1987

A versatile chamber for microphysiologic studies with gas mixtures under high pressure.

A pressure chamber, designed for microelectrode recordings in isolated tissues or organs an capable of withstanding pressures up to 200 bar, is described. The versatility of the vessel allows a wide variety of experimental configurations and several types of studies. It features a complete access, easy visibility, interchangeable tissue bath and micromanipulator modules, as continuous perfusion and temperature control of the preparation under pressure. The ability to move micropipettes in 1-micron steps allows single unit recording on a variety of in vitro preparations at normal or elevated gas pressures. Successful physiologic tests, using the hippocampal slice preparation, are described. The results testify to the reliability of the system and to the usefulness of this in vitro model to study the gas pressure effects on isolated networks of mammalian CNS.

Air Pressure↗
PubMed1985

A study of spontaneous and evoked activity in the rat hippocampus under helium-oxygen high pressure.

High pressures affect the physiology of the central nervous system. For a better understanding of this effect, we examined the hippocampal activity in the rat under high pressures (91 bars) of helium-oxygen. Effects of high pressure on hippocampal physiology are: an abnormally sustained 5-8 Hz pattern of spontaneous activity, followed, in some cases, by seizures; a marked decrease in the responses of CA1 pyramidal cells to stimulation of their commissural afferents; and a 50% decrease in the afterdischarge threshold. On the basis of the relatively well understood hippocampal physiology in normobaric conditions, our observations suggest that high pressures induce hypoexcitability of afferents and/or target cells.

Animals↗
PubMed1983

Classification and properties of acidic amino acid receptors in hippocampus. II. Biochemical studies using a sodium efflux assay.

The properties of excitatory amino acid receptors in hippocampal slices were analyzed using agonist-induced stimulation of 22Na efflux rate. Several amino acids (L- and D-glutamate, N-methylaspartate) produce progressively smaller responses upon successive applications, whereas D,L-homocysteate does not. Several lines of evidence suggest that depletion of an intracellular pool of 22Na is not responsible for the apparent desensitization. Addition of the amino acids in the presence of an antagonist does not affect the response of the slices to subsequent applications, indicating that desensitization is dependent upon the interaction of the agonist with its receptor. The antagonist D-alpha-aminoadipate discriminates between various excitatory amino acids, completely blocking the responses to N-methylaspartate, D-glutamate, and D,L-homocysteate; partially antagonizing those of quisqualate and kainate; and being without effect on L-glutamate. The order of potency of several excitatory amino acids on the stimulation of 22Na efflux rate in hippocampal slices is highly correlated with their relative effects measured with electrophysiological techniques, but does not correlate with their relative potencies to inhibit [3H]glutamate binding to hippocampal membranes. The similarities in the properties of excitatory amino acid receptors evidenced with the 22Na efflux assay or with the electrophysiological approach in the in vitro hippocampal slice preparation indicate that the same receptors are sampled by the two techniques. The results are discussed in terms of a classification of these receptors into four different groups: a synaptic receptor, activated by D,L-homocysteate (tentatively defined as a G1 receptor), an extrasynaptic glutamate receptor (defined as a G2 receptor), an N-methylaspartate receptor, and a kainate receptor.

2-Aminoadipic Acid↗
PubMed1982

The possible mechanisms of the high pressure-induced motor disturbances in the cat.

High pressures elicit a high-frequency tremor (8-12 c/sec) in mammals, the mechanisms of which are still unknown. The present study shows that: (1) in spite of many similarities observed between the EMG characteristics of harmaline-induced tremor and pressure-induced tremor, cerebellar lesions which suppress the harmaline-induced tremor, do not modify the characteristics of the pressure-induced tremor; (2) at depth, the caudal part of the spinal cat (section at T9-T10 spinal level) displays irregular spontaneous EMG activities which can be clonic or rhythmic (4-8 c/sec), and a neuromuscular stretch hyperreflexivity. These data suggest that the origin of the pressure-induced tremor is spinal and neuromuscular rather than cerebellar.

Animals↗
PubMed1982

The blocking action of baclofen on excitatory transmission in the rat hippocampal slice.

The mode of action of baclofen on the physiology of the rat hippocampus was investigated by studying its effect on electrophysiological responses in the hippocampal slice preparation and by measuring biochemical parameters related to glutamate uptake, binding, and release. Baclofen inhibited, in a dose-dependent fashion, the dendritic field potentials in field CA1 produced by stimulation of the Schaffer commissural fiber system. The drug was inactive in this respect at concentrations of 10 and 100 nM but consistently reduced the amplitude of both the dendritic field potential and the population spike at a concentration of 1 microM. At a concentration of 25 microM, baclofen virtually abolished the dendritic and cell body responses to afferent stimulation. Recovery of field potentials required between 7 and 10 min following the addition of 1 microM baclofen. The levorotatory form of baclofen was much more potent in suppressing synaptic responses than was the dextrorotatory enantiomer. Baclofen, at a concentration of 5 microM, strongly antagonized the excitation of pyramidal neurons evoked by iontophoretically applied glutamate. The antagonism of the glutamate effect was much reduced when the slices were maintained in low calcium, high magnesium perfusion medium. Moreover, under low calcium conditions, baclofen did not interfere with the effects of bath-applied glutamate on antidromically elicited responses. Baclofen did not affect the Na+-dependent or Na+-independent binding of [3H]glutamate to crude synaptic membrane fractions from the hippocampus. However, at a concentration of 1 microM, it markedly inhibited potassium-induced release of [3H]glutamate from hippocampal synaptosomes. Taken together, the present results strongly suggest that baclofen suppresses synaptic responses in the Schaffer commissural fiber system of the hippocampus by blocking the release of an excitatory amino acid transmitter.

Action Potentials↗
PubMedDate not supplied

[The role of nitric oxide and superoxides in the neurotoxicity of glutamate].

Glutamate is the major neurotransmitter of the mammalian brain. Stimulation of glutamate receptors, especially the subgroup of NMDA receptors, induces nitric oxide and arachidonic acid synthesis in neurons. These agents freely diffuse across membranes and thus can play roles of messengers in particular brain functions. The aim of our study was to identify these roles in in vitro and in vivo models from mouse and rat. Exaggerated stimulation of NMDA receptors leads to neurological disorders such as some types of epilepsy and neurodegenerative diseases. We show that superoxide ions, which probably result from metabolic degradation of arachidonic acid, would be responsible of the neurotoxic action of NMDA. On the other hand, we observed that nitric oxide inhibits NMDA receptors. This effect would protect animals against epileptic and neurodegenerative diseases mediated by over-stimulation of these receptors. This endogenous regulation may play important roles in the functioning of glutamatergic neurotransmission.

Animals↗