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A Stefani

Publications and source records attributed to A Stefani.

At least 19 recordsLinked to original sources
PubMed1996

L-AP4 inhibits high voltage-activated Ca2+ currents in pyramidal cortical neurones.

We tested the ability of L-AP4 to modulate high voltage-activated (HVA) calcium (Ca2+) currents in pyramidal neurones acutely isolated from the adult rat (4-8 weeks). Whole cell recordings, with barium (Ba2+) ions as the charge carrier, were performed. L-AP4 reduced HVA Ca2+ conductances in 86% of the recorded cells. Saturating concentrations of L-AP4 inhibited about 21% of the current (+/- 8.3%, n = 8), although great variability was observed. Interestingly, low micromolar concentrations of (1S,3R)-1-aminocyclo-pentane-1,3-dicarboxylic acid (1S,3R-ACPD) and (2S,3S,4R)-alpha-(carboxy-cyclopropyl)-glycine (1-CCGI) had weaker effects than L-AP4. MAP4 fully antagonized the L-AP4-mediated reduction of HVA Ca2+ currents. These findings suggest the involvement of the AP4-sensitive receptor in the control of both cellular excitability and transmitter release in rat neocortical neurones.

Amino Acids, Dicarboxylic↗
PubMed1996

A field potential analysis on the effects of lamotrigine, GP 47779, and felbamate in neocortical slices.

We studied the action of the new antiepileptic drugs lamotrigine (LTG), GP 47779 (the active metabolite of oxcarbazepine), and felbamate (FBM) on stimulus-evoked field potentials recorded from rat prefrontal and frontal cortical slices. In the presence of physiologic concentrations of extracellular magnesium (1.2 mM) the field potential amplitude was not affected by the N-methyl-D-aspartate (NMDA) glutamate receptor antagonist, 2-amino-5-phosphonovalerate (APV), while it was blocked by the non-NMDA glutamate receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). When magnesium was removed from the bathing medium, there was a significant NMDA-mediated component of the field potential. LTG and GP 47779 decreased, in a dose-dependent manner, the field potential amplitude under both experimental conditions. FBM caused a dose-related decrease of the field potential amplitude only in the absence of external magnesium, suggesting a selective interaction with an NMDA-mediated component of this potential. These findings indicate that the reduction of cortical excitatory transmission might represent a common target for new antiepileptic drugs.

Animals↗
PubMed1996

Felbamate inhibits dihydropyridine-sensitive calcium channels in central neurons.

The effect of the antiepileptic drug felbamate (FBM) on high-voltage-activated Ca++ currents was studied in cortical and neostriatal neurons acutely isolated from adult rats. Patch-clamp recordings in the whole-cell configuration were performed. Ba++ ions as the charge carrier for Ca++ channels were used. In pyramidal cortical cells, FBM dose-dependently reduced high-voltage-activated Ca++ currents in all the tested neurons. At concentrations of 30 to 100 nM, FBM already produced a significant inhibition of high-voltage-activated Ca++ currents (-6/-15%). At saturating concentrations (1-3 microM), FBM-mediated inhibition averaged 44%. The responses were fully reversible. The dose-response curves revealed IC50 of 504 nM. In striatal neurons, FBM decreased the same conductances by about 28%; the threshold dose was 1 to 2 microM, with an IC50 of 18.7 microM. In both structures, the observed inhibitions were unaffected by omega-conotoxin GVIA and omega-agatoxin IVA, suggesting that N-like channels and P-Like channels were not involved in the FBM-mediated responses. In addition, when omega-conotoxin GVIA and omega-agatoxin IVA (100 nM) were coapplied, the FBM-mediated inhibition on the remaining Ca++ currents averaged 87%. The FBM responses were occluded by micromolar concentrations of nifedipine, supporting a direct interference with dihydropyridine-sensitive channels. It is concluded that the described effect of FBM might represent an efficacious mechanism for either controlling spike discharge from epileptic foci or protecting neurons from excessive Ca++ loading. In both cases, FBM would act as a broad spectrum neuroprotective agent.

Animals↗
PubMed1995

Vulnerability of medium spiny striatal neurons to glutamate: role of Na+/K+ ATPase.

In Huntington's disease neuronal degeneration mainly involves medium-sized spiny neurons. It has been postulated that both excitotoxic mechanisms and energy metabolism failure are implicated in the neuronal degeneration observed in Huntington's disease. In central neurons, > 40% of the energy released by respiration is used by Na+/K+ ATPase to maintain ionic gradients. Considering that impairment of Na+/K+ ATPase activity might alter postsynaptic responsivity to excitatory amino acids (EAAs), we investigated the effects of the Na+/K+ ATPase inhibitors, ouabain and strophanthidin, on the responses to different agonists of EAA receptors in identified medium-sized spiny neurons electrophysiologically recorded in the current- and voltage-clamp modes. In most of the cells both ouabain and strophanthidin (1-3 microM) did not cause significant change in the membrane properties of the recorded neurons. Higher doses of either ouabain (30 microM) or strophanthidin (30 microM) induced, per se, an irreversible inward current coupled to an increase in conductance, leading to cell deterioration. Moreover, both ouabain (1-10 microM) and strophanthidin (1-10 microM) dramatically increased the membrane depolarization and the inward current produced by subcritical concentrations of glutamate, AMPA and NMDA. These concentrations of Na+/K+ ATPase inhibitors also increased the membrane responses induced by repetitive cortical activation. In addition, since it had previously been proposed that dopamine mimics the effects of Na+/K+ ATPase inhibitors and that dopamine agonists differentially regulate the postsynaptic responses to EAAs, we tested the possible modulation of EAA-induced membrane depolarization and inward current by dopamine agonists. Neither dopamine nor selective dopamine agonists or antagonists affected the postsynaptic responses to EAAs. Our experiments show that impairment of the activity of Na+/K+ ATPase may render striatal neurons more sensitive to the action of glutamate, lowering the threshold for the excitotoxic events. Our data support neither the role of dopamine as an ouabain-like agent nor the differential modulatory action of dopamine receptors on the EAA-induced responses in the striatum.

Animals↗
PubMed1995

Properties of the hyperpolarization-activated cation current Ih in rat midbrain dopaminergic neurons.

Intracellular electrophysiological recordings in current- and voltage-clamp mode were obtained from dopaminergic neurons of the rat mesencephalon in an in vitro slice preparation. In current-clamp mode, a time-dependent anomalous rectification (TDR) of the membrane was observed in response to hyperpolarizing current pulses. In single-electrode voltage-clamp mode, a slowly developing inward current (Ih) underlying the TDR was studied by hyperpolarizing voltage commands from a holding potential of -50 to -60 mV. Ih started to be activated at approximately -69 mV, was fully activated at -129 to -141 mV, with half-maximal activation at -87 mV, and showed no inactivation with time. The time course of development of Ih followed a single exponential, and its time constant was voltage-dependent. At -81 mV, Ih activated with a time constant of 379 +/- 47.6 ms, whereas at -129 mV Ih activated with a time constant of 65 +/- 2.2 ms. Its estimated reversal potential was -35 +/- 4 mV. Raising the extracellular concentration of K+ from 2.5 to 6.5 and to 12.5 mM increased the amplitude of Ih while reducing the extracellular concentration of Na+ from 153.2 to 27.2 mM caused a reduction in amplitude of Ih. Bath application of caesium (1-5 mM) reversibly reduced or blocked the TDR/Ih. Perfusion of tetrodotoxin (0.5-1 microM), tetraethylammonium (10-20 mM) or barium (0.3-2 mM) did not significantly affect Ih. Ih was also present in cells impaled with CsCl-filled electrodes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Outward potassium currents activated by depolarization in rat globus pallidus.

Voltage-dependent potassium currents play a key role in shaping the firing pattern of central neurons. Their pharmacological and physiological identification is rather important in the structures which are involved in the filtering of input/output messages. In this regard, globus pallidus external segment (GPe) is indicated as a crucial station in the well-known indirect pathway of the basal ganglia. Among the potassium conductances which have been indicated to condition the firing behavior and the neuronal integrative properties in many central neurons, we analysed the depolarization-activated ones by means of patch-clamp recordings in the whole-cell configuration. Two main families of calcium-independent outward potassium currents are activated by depolarization in GPe neurons acutely isolated from the adult rat. From depolarized holding potentials (-50/-45 mV), a slowly-activating, sustained current is evoked; it manifests very little inactivation and it is available at rather depolarized potentials (-30 mV/-20 mV). This current is relatively resistant to 4-aminopyridine (4-AP) but it is blocked by tetraethilammonium ions (TEA) and consequently it resembles delayed rectifier current (Ik). From negative holding potentials (-80/-100 mV), on the other hand, A-like conductances are activated. Together with a fast-inactivating transient current, another component is observed in a significant proportion of recordings (45%). This current shows half-inactivation voltage around -90 mV, peculiar sensitivity to micromolar doses of 4-AP and a slow rate of recovery from inactivation. The presence and the modulation of these A-like currents may be a very critical aspect in the membrane physiology of pallidal neurons.

4-Aminopyridine↗
PubMed1995

Electrophysiology of dopamine D-1 receptors in the basal ganglia: old facts and new perspectives.

1. The dopamine (DA) D1-receptor family is highly represented in the mammalian brain and particularly in the nigrostriatal system, whose integrity is crucial for the execution of motor performances. 2. In the last decade, our understanding of the electrophysiology of D1 receptors on caudate-putamen neurons has greatly improved. The effects of the activation of striatal D1 receptors were studied by extracellular single unit recordings in the intact animal as well as by intracellular recordings in rat brain slice preparation. More recently, whole-cell recordings on isolated striatal neurons have further addressed this issue and confirmed the inhibitory modulatory role of D1 receptor on the electrical activity of striatal neurons. 3. Several important questions, however, concerning the functional effects of D1 receptor activation in the basal ganglia are still debated: the cellular segregation of the distribution of D1-D2-like receptors, their synergistic or opposite functional roles at the second messenger level, the effects of D1 receptor activation on the transmitter release and the modifications of D1 receptor pharmacology in dopamine-denervated striata. 4. A different perspective will also be discussed: the involvement of D1 receptors in long-term changes of synaptic efficacy in the striatum as a possible correlate of motor learning.

Animals↗
PubMed1995

"Yellow nail syndrome" associated with chronic recurrent pericardial and pleural effusions.

The authors describe a case of yellow nail syndrome in a 44-year-old male patient, with a clinical picture characterized by hand and foot onychodystrophy, lymphedema in the legs and recurrent pleural and pericardial effusions. They indicate subxiphoid pericardiostomy and pleural drainage as the rational surgical procedure for the treatment of this particular associated pathology.

Adult↗
PubMed1995

Electrophysiological actions of felbamate on rat striatal neurones.

1. We have investigated the effects of the anticonvulsant drug, felbamate (FBM), on striatal neurones, recorded in vitro by using both intracellular and extracellular conventional recordings in slices and whole-cell recordings in acutely isolated neurones. 2. FBM, at therapeutically relevant concentrations (30-300 microM) showed multiple mechanisms of action. Like other antiepileptic drugs, FBM (30-300 microM) showed a direct inhibitory action on current-evoked firing discharge of striatal neurones. A patch-clamp analysis of this effect revealed a dose-related reduction of voltage-dependent sodium (Na+) currents (10-100 microM), with a half inhibiton dose (IC50) value of 28 microM. 3. We also tested whether FBM affected corticostriatal glutamate transmission. In control medium (1.2 mM external magnesium), both extracellularly recorded field potentials and intracellularly recorded excitatory postsynaptic potentials (e.p.s.ps) evoked by cortical stimulation were no affected by bath application of 30-300 microM FBM. 4. When magnesium was removed from the perfusing solution, a procedure which reveals a N-methyl-D-aspartate (NMDA)-mediated component in the corticostriatal synaptic potential, FBM (30-300 microM) produced a dose-dependent reduction of the amplitude of both the field potential and the e.p.s.p. 5. FBM reduced the inward currents produced either by bath or by focal applications of 30 microM NMDA, finding consistent with the hypothesis that the observed reduction of the NMDA-mediated component of the synaptic potentials may be caused at postsynaptic level. 6. The reduction of the NMDA-mediated component of the synaptic transmission by FBM and its depressant effect on the voltage-dependent Na+ channels, may account for the antiepileptic action of this drug. Moreover, the pharmacological properties of FBM might render this drug interesting as a neuroprotectant agent.

Action Potentials↗
PubMed1995

Action of GP 47779, the active metabolite of oxcarbazepine, on the corticostriatal system. I. Modulation of corticostriatal synaptic transmission.

Oxcarbazepine (OCBZ) is the keto-analogue of carbamazepine (CBZ). In humans, OCBZ is rapidly and almost completely metabolized to 10, 11-dihydro-10-hydroxy-CBZ (GP 47779), the main metabolite responsible for the drug's antiepileptic activity. The corticostriatal pathway is involved in the propagation of epileptic discharges. We characterized the electrophysiological effects of GP 47779 on striatal neurons by making intracellular recordings from corticostriatal slices. GP 47779 (3-100 microM) produced a dose-dependent inhibition of glutamatergic excitatory postsynaptic potentials (EPSPs). This effect was not coupled either with changes of the membrane potential of these cells or with alterations of their postsynaptic sensitivity to excitatory amino acids (EAA) suggesting a presynaptic site of action. GP 47779 reduced the current-evoked firing discharge only at concentrations > 100 microM. GP 47779 did not affect the presynaptic inhibitory action of adenosine, showing that presynaptic adenosine receptors were not implicated in the GP 47779-mediated reduction of corticostriatal EPSPs. Our data indicate that GP 47779 apparently acts directly on corticostriatal terminals to reduce the release of EAA, probably by inhibiting high-voltage-activated (HVA) calcium (Ca2+) currents (described in the accompanying article). The inhibitory action of GP 47779 on corticostriatal transmission may contribute to the antiepileptic effects of this drug.

Adenosine↗
PubMed1995

Action of GP 47779, the active metabolite of oxcarbazepine, on the corticostriatal system. II. Modulation of high-voltage-activated calcium currents.

GP 47779, the active metabolite of oxcarbazepine (OCBZ) inhibits glutamatergic excitatory postsynaptic potentials (EPSPs) in rat striatum (described in the accompanying article). This effect was presumed to involve the modulation of the calcium (Ca2+) signals at either pre- or postsynaptic level. Therefore, we directly tested whether GP 47779 could modulate Ca2+ conductances in cortical as well as in striatal neurons. GP 47779 produced a reversible dose-dependent decrease in high-voltage-activated (HVA) Ca2+ currents evoked by membrane depolarization in isolated cortical pyramidal cells. GP 47779-mediated reduction in HVA Ca2+ currents, if occurring also at corticostriatal axon terminals, might explain the reduction of glutamate release in the striatum. An inhibitory action of GP 47779 on HVA Ca2+ currents was also observed in isolated striatal neurons. The effect of HVA Ca2+ currents in cortical and striatal neurons persisted in the presence of nifedipine, suggesting that dihydropyridine-sensitive channels were not involved in the GP 47779-mediated responses. We propose that the modulation of HVA Ca2+ channels by this carbamazepine (CBZ) analogue may account for its inhibitory action on transmitter release.

Animals↗
PubMed1995

[Ear prostheses in burns of the external ear. Technical notes].

Ear reconstruction is best performed with autologous tissue. However, there are selected cases in which a prosthesis may be preferred. Some patients are unwilling to undertake multiple surgical procedures, others do not accept the chest wall scar. More importantly, in severe post burn cases, the scars in the periauricular region can truly compromise the outcome of an autologous reconstruction. In such cases, the authors perform a prosthetic reconstruction which is anchored to the cranial bone by means of osteointegrated titanium screws. The method described here has been modified compared to the original Bränemark system. A new microscrew design allows the implants to be inserted in a single surgical procedure. A magnetic anchoring system avoids cumbersome external rods, and the overall size of the masses emerging from the skin is significantly reduced. These improvements increase patient comfort and compliance.

Bioprosthesis↗
PubMed1995

The modulation of dopamine receptors in rat striatum.

In the last decades, the contribution given by basic electrophysiology to the understanding of the nigrostriatal pathway in mammals has been rather important. The main results obtained by our group will be revised in this short review. The most common responses produced by dopamine (DA) on the principal striatal cells (the medium spiny neurons) are the modulation of the corticostriatal synaptic transmission and the decrease of voltage-dependent inward conductances. After blockade of DA transmission, both spontaneous and cortically driven glutamatergic postsynaptic potentials were inhibited by the selective activation of DA D2 receptors. In naive animals, the DA-mediated inhibition of postsynaptic firing activity was mediated by D1 receptor activation. Nevertheless, the two main subclasses of DA receptors seemed to cooperate in the formation of the long-term depression (LTD) of excitatory synaptic transmission in the striatum. The excitotoxic hypothesis of neurodegeneration has further stimulated our interest towards the study of the interactions between DA and other neurotransmitters into the basal ganglia.

Animals↗
PubMed1994

Opioids decrease high-voltage activated calcium currents in acutely dissociated neostriatal neurons.

Although the distribution of opioid receptors is central to the patch-matrix model of neostriatal organization, it has been unclear whether these receptors are located post-synaptically. Moreover, it has not yet been clarified whether opioid receptor activation in neostriatum results in the modulation of calcium and/or potassium conductances. To test this, neostriatal neurons were acutely isolated and their sensitivity to opioid receptor agonists determined. At nanomolar concentrations, both the mu-agonist [D-Ala2, MePhe4,Gly-ol5]-enkephalin (DAMGO) and the delta-agonist [D-Pen2, D-Pen5]-enkephalin (DPEPE) reversibly decreased whole-cell calcium currents in medium-sized neurons. These effects were blocked by the opiate antagonist naloxone. These findings argue that activation of post-synaptic, opioid receptors is capable of modulating the excitability of neostriatal neurons.

Calcium Channels↗
PubMed1994

Effects of dihydropyridine calcium antagonists on rat midbrain dopaminergic neurones.

1. The effects of the dihydropyridine calcium channel antagonists, nifedepine and nimodipine (300 nM-30 microM) were tested in vitro on intracellularly recorded dopaminergic neurones in the rat ventral mesencephalon. 2. Bath applied nifedipine and nimodipine inhibited in a concentration-dependent manner the spontaneous firing discharge of the action potentials, whereas, the dihydropyridine calcium channel agonist, Bay K 8644 increased the firing rate. 3. Pacemaker oscillations and bursts of action potentials were produced by loading the cells with caesium. Nifedipine and nimodipine reduced the rate and the duration of the caesium-induced membrane oscillations and decreased the number of action potentials in a burst. During the blockade of potassium currents the dopaminergic neurones often developed a prolonged (100-800 ms) afterdepolarization that was also inhibited by dihydropyridines. 4. The spontaneous discharge of calcium spikes was also inhibited by both dihydropyridine calcium antagonists. The apparent input resistance and the level of membrane potential were not affected by the dihydropyridine calcium antagonists. 5. If the action potential duration was less than 150 ms the shape of the spike was not clearly influenced by both calcium antagonists. However, when the duration of the action potential was longer than 150-200 ms due to the intracellular injection of caesium ions plus the extracellular application of tetraethylammonium (10-50 mM), both nifedipine and nimodipine reversibly shortened the plateau potential. 6. It is suggested that nifedipine and nimodipine depress the rhythmic and bursting activity of the dopaminergic cells and shorten the calcium action potential by blocking dihydropyridine-sensitive high-threshold calcium currents.

Action Potentials↗