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A Pisani

Publications and source records attributed to A Pisani.

At least 55 records · Page 3Linked to original sources
PubMed2000

Cell-type specificity of mGluR activation in striatal neuronal subtypes.

The effects of metabotropic glutamate receptor (mGluR) activation were studied in medium spiny neurons and large aspiny (LA) interneurons by means of electrophysiological and optical recordings. DCG-IV and L-SOP, agonists for group II and III mGluRs, respectively, produced a presynaptic inhibitory effect on corticostriatal glutamatergic excitatory postsynaptic potentials (EPSPs) in both spiny and LA cells. Activation of group I mGluRs by the selective agonist 3,5-DHPG produced no effect on membrane properties and glutamatergic transmission in spiny neurons, whereas it did cause a membrane depolarization in LA interneurons coupled to increased input resistance. In combined optical and electrophysiological experiments, in spiny neurons 3,5-DHPG enhanced membrane depolarization and intracellular calcium (Ca2+) levels induced by NMDA applications, but not in LA interneurons. These data suggest the existence of a positive interaction between NMDA and group I mGlu receptors only in medium spiny cells which might, at least partially, account for the differential vulnerability to excitotoxic damage observed in striatal neuronal subtypes.

Animals↗
PubMed2000

Anatomical and psychological mechanism of reduplicative misidentification syndromes.

Reduplicative misidentifications syndromes (RMS) are rare memory disorders characterized by the subjective conviction that a place, person or event is duplicated. Even if RMS often follow a right frontal lesion, several studies have stressed the importance of bilateral hemispheric pathology. Moreover, from a psychological perspective, there is uncertainty if this symptom should be considered just as a kind of confabulation or if it should be associated with personal psychosocial and behavioral aspects. We report a patient who developed normal pressure hydrocephalus and RMS one year after a post-traumatic right frontal lesion. At the first neuropsychological evaluation, we found mild impairment of all functions, associated with the presence of reduplicative paramnesia. After the ventricle-peritoneal shunt intervention, we observed a progressive improvement of all functions but the frontal ones. The memory deficit became less specific and the RMS disappeared. We therefore postulate that a focal right frontal lesion is not sufficient to cause RMS per se. Our clinical report suggests that paramnesic events held on reasonable ground, not being just a kind of confabulation.

Aged↗
PubMed2000

Response

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Journal Article↗
PubMed2000

Acetylcholine-mediated modulation of striatal function.

Striatal spiny neurones serve as a major anatomical locus for the relay of cortical information flow through the basal ganglia. these projection neurones also represent the main synaptic target of cholinergic interneurones, whose physiological role in striatal activity still remains largely enigmatic. The striatal cholinergic system has been implicated in the pathophysiology of movement disorders such as Parkinson's disease, but the cellular mechanisms underlying cholinergic-neurone function are still unknown. On the basis of in vitro electrophysiological evidence, obtained from a rat corticostriatal-slice preparation, we propose that endogenous ACh exerts a complex modulation of striatal synaptic transmission, which produces both short-term and long-term effects. ACh-mediated mechanisms might be of crucial importance in processing the cortical inputs to the striatum.

Acetylcholine↗
PubMed2000

Synaptic transmission in the striatum: from plasticity to neurodegeneration.

Striatal neurones receive myriad of synaptic inputs originating from different sources. Massive afferents from all areas of the cortex and the thalamus represent the most important source of excitatory amino acids, whereas the nigrostriatal pathway and intrinsic circuits provide the striatum with dopamine, acetylcholine, GABA, nitric oxide and adenosine. All these neurotransmitter systems interact each other and with voltage-dependent conductances to regulate the efficacy of the synaptic transmission within this nucleus. The integrative action exerted by striatal projection neurones on this converging information dictates the final output of the striatum to the other basal ganglia structures. Recent morphological, immunohistochemical and electrophysiological findings demonstrated that the striatum also contains different interneurones, whose role in physiological and pathological conditions represents an intriguing challenge in these years. The use of the in vitro brain slice preparation has allowed not only the detailed investigation of the direct pre- and postsynaptic electrophysiological actions of several neurotransmitters in striatal neurones, but also the understanding of their role in two different forms of corticostriatal synaptic plasticity, long-term depression and long-term potentiation. These long-lasting changes in the efficacy of excitatory transmission have been proposed to represent the cellular basis of some forms of motor learning and are altered in animal models of human basal ganglia disorders, such as Parkinson's disease. The striatum also expresses high sensitivity to hypoxic-aglycemic insults. During these pathological conditions, striatal synaptic transmission is altered depending on presynaptic inhibition of transmitter release and opposite membrane potential changes occur in projection neurones and in cholinergic interneurones. These ionic mechanisms might partially explain the selective neuronal vulnerability observed in the striatum during global ischemia and Huntington's disease.

Animals↗
PubMed2000

Effects of hydroxymethylglutaryl coenzyme A reductase inhibitor simvastatin on smooth muscle cell proliferation in vitro and neointimal formation in vivo after vascular injury.

OBJECTIVES: We sought to evaluate the effects of hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors on vascular smooth muscle cell (VSMC) proliferation in vitro and neointimal formation in vivo after vascular injury. BACKGROUND: Neointimal hyperplasia after vascular injury is responsible for restenosis after arterial stenting, whereas arterial remodeling and neointimal formation are the causes of restenosis after percutaneous transluminal coronary angioplasty. METHODS: We assessed the effect of simvastatin on in vitro VSMC proliferation. To study the effects of simvastatin in vivo, balloon injury and stent deployment were performed in the common carotid artery of rats. Neointimal area was measured two weeks later in the balloon injury model and three weeks after stent deployment. RESULTS: Simvastatin markedly inhibits VSMC proliferation in vitro. In vivo, simvastatin reduced, in a dose-dependent manner, the neointimal area and the neointima-media ratio after balloon injury from 0.266 +/- 0.015 mm2 to 0.080 +/- 0.026 mm2 and from 1.271 +/- 0.074 to 0.436 +/- 0.158 (p < 0.001 vs. control rats) at the highest dose. Simvastatin also significantly reduced the neointimal formation and the neointima-media ratio after stenting from 0.508 +/- 0.035 mm2 to 0.362 +/- 0.047 mm2 (p < 0.05 vs. control rats) and from 2.000 +/- 0.136 to 1.374 +/- 0.180 (p < 0.05 vs. control rats). The vessel thrombosis rate after stent deployment was 30% in the control group and 11.1% in the treated group (p = NS). Moreover, the systemic administration of simvastatin did not affect hepatic and renal functions, blood pressure or heart rate. CONCLUSIONS: Simvastatin potently inhibits VSMC proliferation in vitro and reduces neointimal formation in a rat model of vascular injury.

Animals↗
PubMed2000

Involvement of intracellular calcium stores during oxygen/glucose deprivation in striatal large aspiny interneurons.

Striatal large aspiny interneurons were recorded from a slice preparation using a combined electrophysiologic and microfluorometric approach. The role of intracellular Ca2+ stores was analyzed during combined oxygen/glucose deprivation (OGD). Before addressing the role of the stores during energy deprivation, the authors investigated their function under physiologic conditions. Trains of depolarizing current pulses caused bursts of action potentials coupled to transient increases in intracellular calcium concentration ([Ca2+]i). In the presence of cyclopiazonic acid (30 micromol/L), a selective inhibitor of the sarcoendoplasmic reticulum Ca2+ pumps, or when ryanodine receptors were directly blocked with ryanodine (20 [micromol/L), the [Ca2+]i transients were progressively smaller in amplitude, suggesting that [Ca2+]i released from intracellular stores helps to maintain a critical level of [Ca2+]i during physiologic firing activity. As the authors have recently reported, brief exposure to combined OGD induced a membrane hyperpolarization coupled to an increase in [Ca2+]i. In the presence of cyclopiazonic acid or ryanodine, the hyperpolarization and the rise in [Ca2+]i induced by OGD were consistently reduced. These data support the hypothesis that Ca2+ release from ryanodine-sensitive Ca2+ pools is involved not only in the potentiation of the Ca2+ signals resulting from cell depolarization, but also in the amplification of the [Ca2+]i rise and of the concurrent membrane hyperpolarization observed in course of OGD in striatal large aspiny interneurons.

Animals↗
PubMed2000

Oral tacrolimus (FK 506) in Crohn's disease complicated by fistulae of the perineum.

We describe the cases of two patients with Crohn's disease affected by severe perineal fistulae resistant to conventional therapies, successfully treated with FK 506, a new immunomodulatory drug. It is well absorbed from diseased bowel and preliminary experiences have indicated its short-term use in complicated Crohn's disease. The first patient was a 24-year-old male with perineal fistula and severe skin ulceration (8 cm of external opening diameter). He had undergone colectomy and ileostomy because of severe pancolitis refractory to medical treatment and had been treated with azathioprine and metronidazole. Two months after starting FK 506, a dramatic improvement made further surgical operation unnecessary. Local and general benefit was observed during the following 26 months, until FK 506 was withdrawn. The second patient was a 28-year-old male with a diagnosis of ulcerative pancolitis changed to Crohn's disease two months after the onset of a perineal fistula, recurring despite drainage procedures, steroid therapy, and total parenteral nutrition. FK 506 was administered for two months with a complete healing of fistula. Successively, it was stopped and corticosteroids (associated to enteral nutrition) were given because of recurrent rectal bleeding. Our experience encourages the use of oral FK 506 in complicated Crohn's disease and suggests the possibility of a long-term primary therapy other than the use as a "bridge" to other treatments.

Administration, Oral↗
PubMed2000

[Pituitary pathology in elderly patients admitted in a division of internal medicine. Description of 3 cases].

Pituitary diseases are often unrecognized in the elderly, although if they can be at the basis of several pathological conditions. We report three clinical cases. Patient n. 1: 87 years old woman, in poor general condition. Thyroid function evaluation showed secondary hypothyroidism. Subsequent pituitary function evaluation demonstrated hypopituitarism with empty sella. The diagnosis was "hypopituitarism with secondary hypothyroidism and adrenocortical insufficiency, in empty sella" starting substitutive treatment with glucocorticoids and L-thyroxine, with improvement in her clinical conditions. Patient n. 2: 74 years old woman, with severe congestive heart failure. Her clinical history revealed hypothyroidism. An endocrine evaluation (in absence of therapy) demonstrated panhypopituitarism with secondary hypothyroidism and adrenocortical insufficiency in presence of empty sella. The patients was started on substitutive treatment and her conditions improved. Patient n. 3: 74 years old man with several atrial fibrillation episodes and hyperthyroidism. Thyroid function evaluation suggested secondary hyperthyroidism confirmed by the presence of a pituitary macroadenoma. The patient underwent surgical adenomectomy by trans-sphenoidal route. The clinical conditions of the patient improved, but a slight secondary hyperthyroidism was still present caused by the persistence of residual pathological tissue in the right cavernous sinus region confirmed by octreoscan suggesting the presence of a lesion endowed with somatostatin receptors. The patient was started on long acting octreotide treatment, which is still in progress. In conclusion, pituitary diseases pass often unrecognized in the elderly. Their prompt recognition and treatment can resolve dangerous situations for the patients.

Adenoma↗
PubMed1999

Weak effect of neuromodulators on climbing fiber-activated [Ca(2+)](i) increases in rat cerebellar Purkinje neurons.

The effect of several neuromodulators (carbachol (CCh), serotonin (5-HT), noradrenaline (NE), and dopamine (DA)) on the climbing fiber (CF)-induced [Ca(2+)](i) increase in the dendrites of cerebellar Purkinje cells was examined in slices from the rat cerebellum. Purkinje cells were filled with the Ca(2+) indicator bis-fura-2 with patch electrodes on the soma. [Ca(2+)](i) changes were measured from regions of interest in the dendrites with a high speed camera. Changes evoked by one or three responses were measured in control conditions and with neuromodulators added to the bath. None of these four classic modulators caused a significant change in the CF-induced [Ca(2+)](i) amplitude. Buspirone, a partial 5-HT(1A) agonist and a weak DA receptor antagonist caused a small (10-15%) reduction in the response.

Animals↗
PubMed1999

A critical role of the nitric oxide/cGMP pathway in corticostriatal long-term depression.

High-frequency stimulation (HFS) of corticostriatal glutamatergic fibers induces long-term depression (LTD) of excitatory synaptic potentials recorded from striatal spiny neurons. This form of LTD can be mimicked by zaprinast, a selective inhibitor of cGMP phosphodiesterases (PDEs). Biochemical analysis shows that most of the striatal cGMP PDE activity is calmodulin-dependent and inhibited by zaprinast. The zaprinast-induced LTD occludes further depression by tetanic stimulation and vice versa. Both forms of synaptic plasticity are blocked by intracellular 1H-[1,2,4]oxadiazolo[4, 3-a]quinoxalin-1-one (ODQ), a selective inhibitor of soluble guanylyl cyclase, indicating that an increased cGMP production in the spiny neuron is a key step. Accordingly, intracellular cGMP, activating protein kinase G (PKG), also induces LTD. Nitric oxide synthase (NOS) inhibitors N(G)-nitro-L-arginine methyl ester hydrochloride (L-NAME) and 7-nitroindazole monosodium salt (7-NINA) block LTD induced by either HFS or zaprinast, but not that induced by cGMP. LTD is also induced by the NO donors S-nitroso-N-acetylpenicillamine (SNAP) and hydroxylamine. SNAP-induced LTD occludes further depression by HFS or zaprinast, and it is blocked by intracellular ODQ but not by L-NAME. Intracellular application of PKG inhibitors blocks LTD induced by HFS, zaprinast, and SNAP. Electron microscopy immunocytochemistry shows the presence of NOS-positive terminals of striatal interneurons forming synaptic contacts with dendrites of spiny neurons. These findings represent the first demonstration that the NO/cGMP pathway exerts a feed-forward control on the corticostriatal synaptic plasticity.

Animals↗
PubMed1999

Metabotropic glutamate receptors and cell-type-specific vulnerability in the striatum: implication for ischemia and Huntington's disease.

Differential sensitivity to glutamate has been proposed to contribute to the cell-type-specific vulnerability observed in neurological disorders affecting the striatum such as Huntington's disease (HD) and global ischemia. Under these pathological conditions striatal spiny neurons are selectively lost while large aspiny (LA) cholinergic interneurons are spared. We studied the electrophysiological effects of metabotropic glutamate receptor (mGluR) activation in striatal spiny neurons and LA interneurons in order to define the role of these receptors in the pathophysiology of the striatum. DCG-IV and L-SOP, agonists for group II and III mGluRs respectively, produced a presynaptic inhibitory effect on corticostriatal glutamatergic excitatory synaptic potentials in both spiny neurons and LA interneurons. Activation of group I mGluRs by the selective agonist 3,5-DHPG produced no detectable effects on membrane properties and glutamatergic synaptic transmission in spiny neurons while it caused a slow membrane depolarization in LA interneurons coupled to increased input resistance. In combined electrophysiological and microfluorometric recordings, 3,5-DHPG strongly enhanced membrane depolarizations and intracellular Ca2+ accumulation induced by NMDA applications in spiny neurons but not in LA interneurons. Activation of protein kinase C (PKC) by phorbol 12,13-diacetate mimicked this latter action of 3,5-DHPG while the facilitatory effect of 3,5-DHPG was prevented by calphostin C, an inhibitor of PKC. These data indicate that a positive interaction between NMDA receptors and group I mGluRs, via PKC activation, is differently expressed in these two neuronal subtypes. Our data also suggest that differential effects of the activation of group I mGluRs, but not of group II and III mGluRs, might partially account for the selective vulnerability to excitotoxic damage observed within the striatum.

Animals↗
PubMed1999

Additive antiproteinuric effect of converting enzyme inhibitor and losartan in normotensive patients with IgA nephropathy.

We tested the hypothesis that the combination of converting enzyme inhibitor (CEI) with losartan (LOS) produces a more profound antiproteinuric effect than either drug alone in normotensive patients with immunoglobulin A (IgA) nephropathy. Eight normotensive (mean blood pressure, 88.9 +/- 2.1 mm Hg) patients with biopsy-proven IgA nephropathy, nonnephrotic proteinuria (protein, 1 to 3 g/d), and normal or slightly reduced creatinine clearance (range, 69 to 119 mL/min) were studied. Clinical evaluations and laboratory tests were performed (1) before CEI treatment (basal) and after (2) CEI alone (CEI, 12 weeks); (3) the combination of CEI and LOS, the latter at a dosage of 50 mg/d (CEI + LOS, 4 weeks); (4) LOS alone (LOS; 50 mg/d; 12 weeks); (5) the combination of LOS and CEI (LOS + CEI, 4 weeks, at the same dosage as CEI + LOS); and (6) a doubled dose of either CEI alone or LOS alone for 4 weeks. CEI and LOS as monotherapy significantly reduced proteinuria by 38% and 30%, respectively. No further reduction of proteinuria was achieved by doubling the dose of CEI or LOS. Both combinations induced a more remarkable reduction of proteinuria (73%; P < 0.05 v other periods) than either drug administered alone. The antiproteinuric effect of CEI or LOS and the more remarkable effect achieved with both combinations was not dependent on the reduction of blood pressure and/or creatinine clearance. In conclusion, this study provides first-time evidence that the combination of CEI and LOS in normotensive patients with IgA nephropathy produces a more profound decrease in proteinuria than either drug. This additive antiproteinuric effect is not dependent on changes in systemic blood pressure and creatinine clearance. Nevertheless, a larger controlled study is required to confirm this novel observation.

Adult↗
PubMed1999

An in vitro electrophysiological study on the effects of phenytoin, lamotrigine and gabapentin on striatal neurons.

We performed intracellular recordings from a rat corticostriatal slice preparation in order to compare the electrophysiological effects of the classical antiepileptic drug (AED) phenytoin (PHT) and the new AEDs lamotrigine (LTG) and gabapentin (GBP) on striatal neurons. PHT, LTG and GBP affected neither the resting membrane potential nor the input resistance/membrane conductance of the recorded cells. In contrast, these agents depressed in a dose-dependent and reversible manner the current-evoked repetitive firing discharge. These AEDs also reduced the amplitude of glutamatergic excitatory postsynaptic potentials (EPSPs) evoked by cortical stimulation. However, substantial pharmacological differences between these drugs were found. PHT was the most effective and potent agent in reducing sustained repetitive firing of action potentials, whereas LTG and GBP preferentially inhibited corticostriatal excitatory transmission. Concentrations of LTG and GBP effective in reducing EPSPs, in fact, produced only a slight inhibition of the firing activity of these cells. LTG, but not PHT and GBP, depressed cortically-evoked EPSPs increasing paired-pulse facilitation (PPF) of synaptic transmission, suggesting that a presynaptic site of action was implicated in the effect of this drug. Accordingly, PHT and GBP, but not LTG reduced the membrane depolarizations induced by exogenously-applied glutamate, suggesting that these drugs preferentially reduce postsynaptic sensitivity to glutamate released from corticostriatal terminals. These data indicate that in the striatum PHT, LTG and GBP decrease neuronal excitability by modulating multiple sites of action. The preferential modulation of excitatory synaptic transmission may represent the cellular substrate for the therapeutic effects of new AEDs whose use may be potentially extended to the therapy of neurodegenerative diseases involving the basal ganglia.

Acetates↗
PubMed1999

Electrophysiological recordings and calcium measurements in striatal large aspiny interneurons in response to combined O2/glucose deprivation.

Electrophysiological recordings and calcium measurements in striatal large aspiny interneurons in response to combined O2/glucose deprivation. The effects of combined O2/glucose deprivation were investigated on large aspiny (LA) interneurons recorded from a striatal slice preparation by means of simultaneous electrophysiological and optical recordings. LA interneurons were visually identified and impaled with sharp microelectrodes loaded with the calcium (Ca2+)-sensitive dye bis-fura-2. These cells showed the morphological, electrophysiological, and pharmacological features of large striatal cholinergic interneurons. O2/glucose deprivation induced a membrane hyperpolarization coupled to a concomitant increase in intracellular Ca2+ concentration ([Ca2+]i). Interestingly, this [Ca2+]i elevation was more pronounced in dendritic branches rather than in the somatic region. The O2/glucose-deprivation-induced membrane hyperpolarization reversed its polarity at the potassium (K+) equilibrium potential. Both membrane hyperpolarization and [Ca2+]i rise were unaffected by TTX or by a combination of ionotropic glutamate receptors antagonists, D-2-amino-5-phosphonovaleric acid and 6cyano-7-nitroquinoxaline-2, 3-dione. Sulfonylurea glibenclamide, a blocker of ATP-sensitive K+ channels, markedly reduced the O2/glucose-deprivation-induced membrane hyperpolarization but failed to prevent the rise in [Ca2+]i. Likewise, charybdotoxin, a large K+-channel (BK) inhibitor, abolished the membrane hyperpolarization but did not produce detectable changes of [Ca2+]i elevation. A combination of high-voltage-activated Ca2+ channel blockers significantly reduced both the membrane hyperpolarization and the rise in [Ca2+]i. In a set of experiments performed without dye in the recording electrode, either intracellular bis-(o-aminophenoxy)-N,N,N',N'-tetraacetic acid or external barium abolished the membrane hyperpolarization induced by O2/glucose deprivation. The hyperpolarizing effect on membrane potential was mimicked by oxotremorine, an M2-like muscarinic receptor agonist, and by baclofen, a GABAB receptor agonist. However, this membrane hyperpolarization was not coupled to an increase but rather to a decrease of the basal [Ca2+]i. Furthermore glibenclamide did not reduce the oxotremorine- and baclofen-induced membrane hyperpolarization. In conclusion, the present results suggest that in striatal LA cells, O2/glucose deprivation activates a membrane hyperpolarization that does not involve ligand-gated K+ conductances but is sensitive to barium, glibenclamide, and charybdotoxin. The increase in [Ca2+]i is partially due to influx through voltage-gated high-voltage-activated Ca2+ channels.

Animals↗
PubMed1999

Sodium influx plays a major role in the membrane depolarization induced by oxygen and glucose deprivation in rat striatal spiny neurons.

BACKGROUND AND PURPOSE: Striatal spiny neurons are selectively vulnerable to ischemia, but the ionic mechanisms underlying this selective vulnerability are unclear. Although a possible involvement of sodium and calcium ions has been postulated in the ischemia-induced damage of rat striatal neurons, the ischemia-induced ionic changes have never been analyzed in this neuronal subtype. METHODS: We studied the effects of in vitro ischemia (oxygen and glucose deprivation) at the cellular level using intracellular recordings and microfluorometric measurements in a slice preparation. We also used various channel blockers and pharmacological compounds to characterize the ischemia-induced ionic conductances. RESULTS: Spiny neurons responded to ischemia with a membrane depolarization/inward current that reversed at approximately -40 mV. This event was coupled with an increased membrane conductance. The simultaneous analysis of membrane potential changes and of variations in [Na+]i and [Ca2+]i levels showed that the ischemia-induced membrane depolarization was associated with an increase of [Na+]i and [Ca2+]i. The ischemia-induced membrane depolarization was not affected by tetrodotoxin or by glutamate receptor antagonists. Neither intracellular BAPTA, a Ca2+ chelator, nor incubation of the slices in low-Ca2+-containing solutions affected the ischemia-induced depolarization, whereas it was reduced by lowering the external Na+ concentration. High doses of blockers of ATP-dependent K+ channels increased the membrane depolarization observed in spiny neurons during ischemia. CONCLUSIONS: Our findings show that, although the ischemia-induced membrane depolarization is coupled with a rise of [Na+]i and [Ca2+]i, only the Na+ influx plays a prominent role in this early electrophysiological event, whereas the increase of [Ca2+]i might be relevant for the delayed neuronal death. We also suggest that the activation of ATP-dependent K+ channels might counteract the ischemia-induced membrane depolarization.

Adenosine Triphosphate↗
PubMed1999

Pharmacological inhibition of the Na(+)/Ca(2+) exchanger enhances depolarizations induced by oxygen/glucose deprivation but not responses to excitatory amino acids in rat striatal neurons.

BACKGROUND AND PURPOSE: Neuronal Na(+)/Ca(2+) exchanger plays a relevant role in maintaining intracellular Ca(2+) and Na(+) levels under physiological and pathological conditions. However, the role of this exchanger in excitotoxicity and ischemia-induced neuronal injury is still controversial and has never been studied in the same neuronal subtypes. METHODS: We investigated the effects of bepridil and 3',4'-dichlorobenzamil (DCB), 2 blockers of the Na(+)/Ca(2+) exchanger, in rat striatal spiny neurons by utilizing intracellular recordings in brain slice preparations to compare the action of these drugs on the membrane potential changes induced either by oxygen and glucose deprivation (OGD) or by excitatory amino acids (EAAs). RESULTS: Bepridil (3 to 100 micromol/L) and DCB (3 to 100 micromol/L) caused a dose-dependent enhancement of the OGD-induced depolarization measured in striatal neurons. The EC(50) values for these effects were 31 micromol/L and 29 micromol/L, respectively. At these concentrations neither bepridil nor DCB altered the resting membrane properties of the recorded cells (membrane potential, input resistance, and current-voltage relationship). The effects of bepridil and DCB on the OGD-induced membrane depolarization persisted in the presence of D-2-amino-5-phosphonovalerate (50 micromol/L) plus 6-cyano-7-nitroquinoxaline-2,3-dione (20 micromol/L), which suggests that they were not mediated by an enhanced release of EAAs. Neither tetrodotoxin (1 micromol/L) nor nifedipine (10 micromol/L) affect the actions of these 2 blockers of the Na(+)/Ca(2+) exchanger, which indicates that voltage-dependent Na(+) channels and L-type Ca(2+) channels were not involved in the enhancement of the OGD-induced depolarization. Conversely, the OGD-induced membrane depolarization was not altered by 5-(N, N-hexamethylene) amiloride (1 to 3 micromol/L), an inhibitor of the Na(+)/H(+) exchanger, which suggests that this antiporter did not play a prominent role in the OGD-induced membrane depolarization recorded from striatal neurons. Bepridil (3 to 100 micromol/L) and DCB (3 to 100 micromol/L) did not modify the amplitude of the excitatory postsynaptic potentials evoked by cortical stimulation. Moreover, these blockers did not affect membrane depolarizations caused by brief applications of glutamate (0.3 to 1 mmol/L), AMPA (0. 3 to 1 micromol/L), and NMDA (10 to 30 micromol/L). CONCLUSIONS: These results provide pharmacological evidence that the activation of the Na(+)/Ca(2+) exchanger exerts a protective role during the early phase of OGD in striatal neurons, although it does not shape the amplitude and the duration of the electrophysiological responses of these cells to EAA.

Amiloride↗