Biomedical subjects

H Katsuki

Publications and source records attributed to H Katsuki.

At least 37 records · Page 2Linked to original sources

PubMed1999

Depletion of intracellular glutathione increases susceptibility to nitric oxide in mesencephalic dopaminergic neurons.

Using primary neuronal cultures, we investigated the effects of GSH depletion on the cytotoxic effects of glutamate and NO in dopaminergic neurons. Intracellular GSH was depleted by 24-h exposure to L-buthionine-[S,R]-sulfoximine (BSO), an irreversible inhibitor of GSH synthase. BSO exposure caused concentration-dependent reduction of the viability of both dopaminergic and nondopaminergic neurons. In contrast, 24-h exposure of cultures to glutamate or NOC18, an NO-releasing agent, significantly reduced the viability of nondopaminergic neurons without affecting that of dopaminergic neurons. Pretreatment with N-acetyl-L-cysteine for 24 h ameliorated the NOC18-induced toxicity in nondopaminergic neurons. In dopaminergic neurons, sublethal concentrations of BSO reduced intracellular GSH content and markedly potentiated glutamate- and NOC18-induced toxicity. These results suggested that glutamate toxicity was enhanced in dopaminergic neurons by suppression of defense mechanisms against NO toxicity under conditions of GSH depletion. Under such conditions, free iron plays an important role because BSO-enhanced NO toxicity was ameliorated by the iron-chelating agent, deferoxamine. These results suggest that GSH plays an important role in the expression of NO-mediated glutamate cytotoxicity in dopaminergic neurons. Free iron may be related to enhanced NO cytotoxicity under GSH depletion.

Animals↗

PubMed1999

[Factors regulating survival and death of midbrain dopamine neurons].

We utilized organotypic midbrain slice cultures for the assessment of survival and degeneration of dopaminergic neurons in the substantia nigra. Application of N-methyl-D-aspartate (NMDA) to midbrain slice cultures for 24 h caused a concentration-dependent decrease in the number of surviving dopaminergic neurons visualized by tyrosine hydroxylase immunohistochemistry. Simultaneous application of (-)-deprenyl significantly attenuated the cytotoxic effect of NMDA. Because pretreatment with (-)-deprenyl failed to reduce NMDA toxicity, it is suggested that the neuroprotective effect of (-)-deprenyl is not mediated by its irreversible inhibitory action on monoamine oxidase B. We also prepared co-cultures of midbrain and striatal slices to investigate whether the presence of target tissue influences toxic actions of several drugs on dopaminergic neurons. Co-cultured dopaminergic neurons formed dense innervation to the striatal tissue. Dopaminergic neurons in midbrain--striatum co-cultures were more resistant to the cytotoxic actions of NMDA and a nitric oxide donor NOC-18, than the same neuronal population in single midbrain cultures. On the other hand, the toxicity of 1-methyl-4 phenylpyridinium ion or buthionine-[S,R]-sulfoximine was more prominent in midbrain--striatum co-cultures than that in single midbrain cultures. Organotypic slice cultures appeared to be a useful system for evaluation of dopaminergic neuronal death under experimental conditions relevant to physiological/pathophysiological situations.

1-Methyl-4-phenylpyridinium↗

PubMed1998

A potential role of Ras-mediated signal transduction for the enhancement of depolarization-induced Ca2+ responses in hippocampal neurons by basic fibroblast growth factor.

Chronic treatment with basic fibroblast growth factor (bFGF) increases the expression of functional L-type voltage-dependent Ca2+ channels (VDCCs) in fetal rat hippocampal neurons. We investigated the intracellular signaling mechanisms involved in this effect, using high K+ depolarization-induced elevation of intracellular Ca2+ concentrations as a measure. Genistein, a protein tyrosine kinase inhibitor, significantly attenuated the effect of bFGF. The effect of bFGF was also diminished by concurrent application of a Ras inactivator, N-acetyl-S-farnesyl-l-cysteine. In contrast, a phospholipase C inhibitor U73122, a phosphatidylinositol-3 kinase inhibitor wortmannin, Li+ which inhibits inositol phospholipid turnover, or a protein kinase inhibitor calphostin C did not inhibit the effect of bFGF. Phorbol 12-myristate 13-acetate, a protein kinase C activator, did not mimic the effect of bFGF. On the other hand, an adenylyl cyclase activator forskolin and a cyclic AMP analog 8-Br-cyclic AMP markedly attenuated the effect of bFGF, which indicates the presence of a cyclic AMP-mediated negative regulatory mechanism, possibly the interference of Ras-Raf interaction. These results suggest that Ras-mediated signal transduction is required for the enhancement by bFGF of VDCC responses in hippocampal neurons.

8-Bromo Cyclic Adenosine Monophosphate↗

PubMed1998

beta-Hydroxybutyrate fuels synaptic function during development. Histological and physiological evidence in rat hippocampal slices.

To determine whether ketone bodies sustain neuronal function as energy substrates, we examined the effects of beta-hydroxybutyrate (betaHB) on synaptic transmission and morphological integrity during glucose deprivation in rat hippocampal slices. After the depression of excitatory postsynaptic potentials (EPSPs) by 60 min of glucose deprivation, administration of 0.5-10 mM D-betaHB restored EPSPs in slices from postnatal day (PND) 15 rats but not in slices from PND 30 or 120 rats. At PND 15, adding D-betaHB to the media allowed robust long-term potentiation of EPSPs triggered by high frequency stimulation, and prevented the EPSP-spike facilitation that suggests hyperexcitability of neurons. Even after PND 15,D-betaHB blocked morphological changes produced by either glucose deprivation or glycolytic inhibition. These results indicate that D-betaHB is not only able to substitute for glucose as an energy substrate but is also able to preserve neuronal integrity and stability, particularly during early development.

3-Hydroxybutyric Acid↗

PubMed1998

3-Hydroxykynurenine, an endogenous oxidative stress generator, causes neuronal cell death with apoptotic features and region selectivity.

3-Hydroxykynurenine (3-HK) is a potential endogenous neurotoxin whose increased levels have been described in several neurodegenerative disorders. Here, we characterized in vitro neurotoxicity of 3-HK. Of the tested kynurenine pathway metabolites, only 3-HK, and to a lesser extent 3-hydroxyanthranilic acid, were toxic to primary cultured striatal neurons. 3-HK toxicity was inhibited by various antioxidants, indicating that the generation of reactive oxygen species is essential to the toxicity. 3-HK-induced neuronal cell death showed several features of apoptosis, as determined by the blockade by macromolecule synthesis inhibitors, and by the observation of cell body shrinkage with nuclear chromatin condensation and fragmentation. In addition, 3-HK toxicity was dependent on its cellular uptake via transporters for large neutral amino acids, because uptake inhibition blocked the toxicity. Cortical and striatal neurons were much more vulnerable to 3-HK toxicity than cerebellar neurons, which may be attributable to the differences in transporter activities of these neurons. These results indicate that 3-HK, depending on transporter-mediated cellular uptake and on intracellular generation of oxidative stress, induces neuronal cell death with brain region selectivity and with apoptotic features, which may be relevant to pathology of neurodegenerative disorders.

Amino Acid Transport Systems↗

PubMed1998

Graded, irreversible changes in crayfish giant axon as manifestations of lidocaine neurotoxicity in vitro.

UNLABELLED: High concentrations of lidocaine induce irreversible conduction block with little effect on resting membrane potential (Em). We assumed the mechanism of persistent neurologic deficit caused by local anesthetics may result from neural death, as represented by the loss of Em. We investigated the effects of lidocaine on Em and action potential (AP) in single crayfish giant axons in vitro. Axons were perfused with two doses of lidocaine for either 15 or 30 min, and they were continuously washed. No axons exposed to 80 mM lidocaine for 30 min showed recovery of AP and Em. Those exposed to 40 mM for 30 min and 80 mM for 15 min showed a return to baseline for Em, but no recovery of AP. Those exposed to 40 mM lidocaine for 15 min showed full recovery of Em and AP immediately after washing. The membrane depolarization was significantly greater during exposure to 80 mM lidocaine for 30 min than in other groups. We conclude that lidocaine has a direct neurotoxic effect on crayfish giant axons and that the generation of AP is more vulnerable than the maintenance of Em. The irreversibility of AP and Em is dose- and time-dependent. IMPLICATIONS: Highly concentrated lidocaine induced an irreversible conduction block and a complete loss of resting membrane potential in crayfish giant axons in vitro. Our results may represent a possible explanation for various grades of local anesthetic-induced neurotoxicity in clinical cases if the same toxicity occurs in mammalian nerves in vivo.

Action Potentials↗

PubMed1998

The effects of extracellular pH with and without bicarbonate on intracellular procaine concentrations and anesthetic effects in crayfish giant axons.

BACKGROUND: The potentiating effect of sodium bicarbonate on local anesthetic action is attributed to two mechanisms: (1) an increase in the un-ionized local anesthetic due to extracellular alkalinization, and (2) an accelerated conversion of local anesthetic from un-ionized to ionized form with intracellular acidification caused by bicarbonate. To evaluate these hypotheses, the intracellular pH, intracellular ionized procaine concentration, and evoked action potentials were measured in crayfish giant axons. METHODS: In all measurements, axon preparations from crayfish were perfused extracellularly for 15 min with either bicarbonate-containing solution at pH 7.6 (bicarb/7.6) or bicarbonate-free solution at pH 7.6 (nonbicarb/7.6) or pH 8.0 (nonbicarb/8.0). Intracellular pH was measured using a pH-sensitive microelectrode. Intracellular anesthetic concentration was measured using a specially designed procaine-sensitive microelectrode with each of three solutions containing 1 mM procaine hydrochloride. Membrane potential was measured and, as an index of anesthetic action, the dV/dt of evoked action potential was calculated during perfusion with procaine. RESULTS: Mean intracellular pH was significantly lower in the bicarb/7.6 (7.16+/-0.07) group than in the nonbicarb/7.6 (7.33+/-0.09) and nonbicarb/8.0 (7.33+/-0.12) groups (P < 0.01). The mean intracellular ionized procaine concentration was significantly higher in the bicarb/7.6 (0.53+/-0.08 mM; P < 0.05) and nonbicarb/8.0 (0.58+/-0.13 mM; P < 0.01) than in nonbicarb/7.6 (0.32+/-0.14 mM) group but did not differ between the bicarb/7.6 and nonbicarb/8.0 groups. The mean percentage decrease in dV/dtmax was approximately coincident with the mean intracellular procaine concentration in each solution. CONCLUSION: The presence of bicarbonate or extracellular alkalinization increased the intracellular concentration of ionized procaine and the anesthetic effect.

Action Potentials↗

PubMed1998

Oxygen deprivation produces delayed inhibition of long-term potentiation by activation of NMDA receptors and nitric oxide synthase.

The acute and delayed effects of anoxia on synaptic transmission and long-term potentiation (LTP) were examined in the CA1 region of rat hippocampal slices. Oxygen deprivation for 20 minutes completely but reversibly depressed excitatory postsynaptic potentials mediated by both N-methyl-D-aspartate receptors (NMDAR) and non-NMDAR. Although LTP was reliably produced by a single tetanus delivered 30 minutes after reoxygenation, LTP could not be induced when a tetanus was delivered 70 to 100 minutes after reoxygenation. A tetanus delivered 100 minutes after reoxygenation produced lasting synaptic enhancement when 100 mumol/L D,L-amino-phosphonovaleric acid (APV), a competitive NMDAR antagonist, was administered during the period of oxygen deprivation. The delayed effects of oxygen deprivation were not blocked when APV was administered after oxygen deprivation. Similarly, the delayed effects on LTP induction were overcome by inhibitors of nitric oxide synthase when the nitric oxide synthase inhibitors were administered during anoxia, but not when administered after oxygen deprivation. These results suggest that untimely activation of NMDAR and nitric oxide release during anoxia produce delayed inhibition of LTP induction and may be involved in the memory defects that occur subsequent to cerebral hypoxia.

Animals↗

PubMed1998

Pharmacokinetic differences between lansoprazole enantiomers in rats.

Because limited information is available about potential differences between the pharmacokinetics and pharmacodynamics of the enantiomers of lansoprazole, the enantioselective pharmacokinetics of the compound have been investigated in rats. There was a noticeable difference between the serum levels of the enantiomers of lansoprazole and of their metabolites, 5-hydroxylansoprazole enantiomers, after oral administration of the racemate (50 mg kg(-1)) to rats. Cmax (maximum serum concentration) and AUC (area under the serum concentration-time curve) for (+)-lansoprazole were 5-6 times greater than those for (-)-lansoprazole, whereas for (+)-5-hydroxylansoprazole both values were significantly smaller than those for the (-) enantiomer. CLtot/F values (where CLtot is total clearance and F is the fraction of the dose absorbed) for (+)-lansoprazole were significantly smaller than those for the (-) enantiomer. There was no significant difference between the absorption rate constants of the lansoprazole enantiomers in the in-situ absorption study. The in-vitro protein-binding study showed that binding of (+)-lansoprazole to rat serum proteins was significantly greater than for the (-) enantiomer. The in-vitro metabolic study showed that the mean metabolic ratio (45.9%) for (-)-lansoprazole was significantly greater than that (19.8%) for the (+) enantiomer in rat liver microsomes at 5.6 microM lansoprazole. These results show that the enantioselective disposition of lansoprazole could be a consequence of the enantioselectivity of plasma-protein binding and the hepatic metabolism of the enantiomers.

2-Pyridinylmethylsulfinylbenzimidazoles↗

PubMed1998

[Protective effect of neurotrophin against glutamate neurotoxicity in cortical cultures].

This study was performed to investigate the effects of neurotrophins on glutamate cytotoxicity by using cultured cortical neurons. Primary cultures obtained from the cerebral cortex of fetal rats (17-19 days gestation) were used for experiments. NGF did not elicit tyrosine phosphorylation of Trks whereas BDNF induced Trk tyrosine phosphorylation within 10 min, followed by time-dependent decrease. Brief glutamate exposure to the cell induced delayed cytotoxicity. Similar cytotoxicity was observed with the brief application of a calcium ionophore, ionomycin, and nitric oxide (NO) generating agents, S-nitrosocysteine (SNOC) and SIN-1. Exposure of the cultures to NGF and BDNF for 1 or 24 hr prior to glutamate exposure reduced glutamate-induced cytotoxicity. In contrast, simultaneous addition of NGF and BDNF with glutamate did not affect glutamate-induced cytotoxicity. Ionomycin-induced cytotoxicity was prevented by exposing cultures to NGF and BDNF for 24-hr. Moreover, NGF and BDNF ameliorated cytotoxicity induced by SNOC and SIN-1. These results suggest that neurotrophins prevent NO mediated glutamate cytotoxicity.

Animals↗

PubMed1997

Endogenous monocarboxylates sustain hippocampal synaptic function and morphological integrity during energy deprivation.

The ability to fuel neurons via glycogenolysis is believed to be an important function of glia. Indeed, the slow, rather than immediate, depression of synaptic transmission in hippocampal slices during exogenous glucose deprivation suggests that intrinsic energy reservoirs help to sustain neurotransmission. It is believed that glia fuel neighboring neurons via diffusible monocarboxylates such as pyruvate and lactate, although a role for glucose has been proposed also. Using alpha-cyano-4-hydroxycinnamate (4-CIN) to inhibit monocarboxylate transport and cytochalasin B (CCB) to inhibit glucose transport, we examined the role of glucose and monocarboxylates in supporting the functional and morphological integrity of hippocampal neurons during glucose deprivation. Although 200 microM 4-CIN failed to depress EPSPs supported by 10 mM glucose, pretreatment with 4-CIN accelerated the depression of EPSPs during glucose deprivation. 4-CIN also accelerated the decline in glucose-supported EPSPs after administration of 50 microM CCB, whereas CCB failed to alter the slow decay of pyruvate-supported EPSPs during pyruvate deprivation. 4-CIN did not alter the morphology of pyramidal neurons in the presence of 10 mM glucose but produced significant damage during glucose deprivation or CCB administration. These results suggest that endogenous monocarboxylates rather than glucose maintain neuronal integrity during energy deprivation. Furthermore, EPSPs supported by 2-3.3 mM glucose were sensitive to 4-CIN, suggesting that endogenous monocarboxylates are involved in maintaining neuronal function even under conditions of mild glucose deprivation.

Animals↗

PubMed1997

Biphasic effect of hydrogen peroxide on field potentials in rat hippocampal slices.

In the CA1 region of rat hippocampal slices, H2O2 (0.294-2.94 mM) caused initial augmentation, and subsequent long-lasting depression, of population spikes and excitatory postsynaptic potentials. The effect of H2O2 may not be mediated by its degradation product, hydroxyl radicals, because an iron chelator deferoxamine did not block the effect. A catalase inhibitor 3-amino-1,2,4-triazole only modestly attenuated the initial augmentation, suggesting that the effect of H2O2 is not attributable to catalase-dependent O2 generation, either. An N-methyl-D-aspartate receptor antagonist DL-2-amino-5-phosphonovaleric acid had no influence on the effect of H2O2, whereas a gamma-aminobutyric acid type A receptor channel blocker picrotoxin attenuated long-lasting depression, indicating that gamma-aminobutyric acid-mediated inhibition is altered during the depression phase. The initial augmentation but not subsequent depression was attenuated by a phospholipase A2/C inhibitor 4-bromophenacyl bromide, suggesting the involvement of lipid signaling molecule(s) in the enhancement of excitatory synaptic transmission. These results suggest that H2O2 regulates hippocampal synaptic transmission via multiple mechanisms.

Action Potentials↗

PubMed1997

Monocarboxylates (pyruvate and lactate) as alternative energy substrates for the induction of long-term potentiation in rat hippocampal slices.

We previously reported that mild hypoglycemic conditions hamper the induction of long-term potentiation (LTP) in the CA1 region of rat hippocampal slices. In the present study, we examined whether monocarboxylates (pyruvate and lactate) permit LTP induction when glucose is unavailable. During glucose deprivation, pyruvate and lactate not only maintained basal synaptic transmission but also allowed LTP induction, with pyruvate being more effective than lactate. Additionally, LTP inhibition by 5 microM iodoacetate, a glycolytic inhibitor, was prevented by addition of pyruvate but not lactate. These results suggest that monocarboxylates can be affected alternative energy substrates for LTP induction when glucose is not available. However, lactate and pyruvate are not identical as energy sources for LTP induction.

Animals↗

PubMed1997

Monocarboxylic acids enhance the anesthetic action of procaine by decreasing intracellular pH.

Sodium monocarboxylates are known to enhance the anesthetic action of procaine, and also decrease intracellular pH (pHi). We studied the effect of 30 mM Na monocarboxylates (formate, acetate, propionate, butyrate, and salicylate) on the pHi and on the anesthetic action of procaine HCl using giant axons of crayfish (Procambarus clarkii). The pHi was measured using pH sensitive microelectrode method and the anesthetic action was evaluated by the change in the action potential (AP) amplitude. The tested acids except for formate showed apparent decrease in pHi and enhancement of the action of 2 mM procaine. Other organic acids (maleate and benzensulfonate) did not affect pHi and anesthetic action of procaine. In the bicarbonate free solution, pHi increased and the anesthetic action was weakened. The EC25 values (the concentration of procaine which depresses the AP amplitude by 25%) of acetate, propionate, and bicarbonate free solution were coincided with the predicted EC25 values from the simple simulation on intracellular procaine increase according to the pHi change. But the EC25 value of salicylate group was less than half of the predicted. These results suggested that the enhancing action of straight chain monocarboxylic acids is due to pHi decrease, and salicylate has other additional mechanisms.

Action Potentials↗

PubMed1997

GABAA receptor stimulation promotes survival of embryonic rat striatal neurons in culture.

In order to clarify the functional role of gamma-aminobutyric acid (GABA) in developing brain, we investigated the effect of GABA on the survival of embryonic rat striatal neurons in dissociated cell culture. Chronic exposure of striatal cultures to GABA resulted in a significant increase in the number of surviving neurons. The effect of GABA was concentration-dependent (1-1000 microM) and was blocked by a GABAA receptor antagonist, bicuculline (100 microM), or a GABAA chloride channel blocker, picrotoxin (100 microM), but not by a GABAB receptor antagonist, 2-hydroxysaclofen (100 microM). In addition, the GABAA receptor agonist muscimol mimicked the effect of GABA, promoting cell survival in a concentration-dependent manner (0.01-100 microM), while the GABAB receptor agonist baclofen (up to 100 microM) had no significant effect. The GABA-induced enhancement of neuronal survival was suppressed by the L-type voltage-dependent Ca2+ channel blockers nifedipine (1-3 microM) and nicardipine (1-5 microM). Protein kinase inhibitors, H-7 (10-30 microM) or genistein (3 microM), also suppressed GABA-induced enhancement of neuronal survival. These results suggest that stimulation of GABAA receptors enhances survival of embryonic striatal neurons, and that the effect is mediated by Ca2+ influx through L-type voltage-dependent Ca2+ channels, initiating intracellular signaling cascades that involve activation of H-7- and genistein-sensitive protein kinases.

Animals↗

PubMed1997

Genetic polymorphism of CYP2C19 and lansoprazole pharmacokinetics in Japanese subjects.

OBJECTIVE: We investigated whether interindividual differences in the pharmacokinetic disposition of lansoprazole are attributed to the genetic polymorphism of CYP2C19 which occurred by two mutations. CYP2C19m1 and CYP2C19m2, in 20 Japanese subjects. METHODS: Polymerase chain reaction (PCR) restriction fragment length polymorphism procedures were used to detect the CYP2C19m1 mutation in exon 5 and the CYP2C19m2 mutation in exon 4 using SmaI and BamHI, respectively. RESULTS: Ten subjects were homozygous (wt/wt subjects) for the wt allele in both exon 5 and exon 4, four subjects were heterozygous (wt/m1) for the CYP2C19m1 mutation, and two subjects were heterozygous (wt/m2) for the CYP2C19m2. The remaining four subjects had both mutated alleles in CYP2C19 genes, i.e., two were homozygous (m1/m1) for the defect in exon 5 and two were heterozygous (m1/m2) for the two defects in exons 5 and 4. The subjects in group 1 (wt/wt, wt/m1 and wt/m2) were the extensive metabolizers (EMs) for 5-hydroxylation of lansoprazole and were in the range of hydroxylation indexes from 3.83 to 19.8, whereas the subjects in group 2 (m1/m1 and m1/m2) were the poor metabolizers (PMs) and the indexes were in the range of 38.5 to 47.6. In group 2, AUC, t1/2 and CL/f of lansoprazole were significantly greater, longer, and lower, respectively, than those in group 1.

2-Pyridinylmethylsulfinylbenzimidazoles↗

PubMed1997

Allixin, a phytoalexin produced by garlic, and its analogues as novel exogenous substances with neurotrophic activity.

Effects of allixin, a phytoalexin of garlic, and its analogues were studied on the survival and morphology of primary cultured neurons from fetal rat brain. Addition of allixin (1-100 ng/ml) to medium significantly promoted the survival of neurons derived from various regions of brain and increased the number of branching points per axon in hippocampal neurons. Allixin, however, was cytotoxic at higher concentrations (>1 microg/ml). Among the analogues of allixin, 2,6-dimethyl-3-hydroxy-4H-pyran-4-one (DHP) possessed potent neurotrophic activity at concentrations over 10 ng/ml without any obvious cytotoxicity up to 10 microg/ml. DHP also retained the activity to promote axonal branching. These results indicate that DHP is a novel exogenous low molecular weight neurotrophic substance without apparent cytotoxicity. This compound may be a useful prototype leading chemical for developing therapeutic and/or prophylactic drugs for neurodegenerative disorders.

Animals↗

PubMed1997

Removal of extracellular calcium after conditioning stimulation disrupts long-term potentiation in the CA1 region of rat hippocampal slices.

During a conditioning stimulus, the influx of Ca2+ into neurons appears to be crucial for the induction of long-term potentiation at CA1 hippocampal synapses. We report here that extracellular Ca2+ is also required for full production of long-term potentiation during a critical period following the conditioning stimulus. In control slices, removal of extracellular Ca2+ (0 mM Ca2+/10 mM Mg2+) for 15 min eliminated synaptic transmission. Following reintroduction of normal extracellular solution, synaptic responses recovered fully within 15 min. However, removal of extracellular Ca2+ 15-30 min after theta burst stimulation significantly decreased the magnitude of long-term potentiation. A time window seems to exist for this effect, since either earlier or later Ca2+ removal was less effective. The effect of the 0 mM Ca2+/10 mM Mg2+ solution was observed in the absence of afferent stimulation, suggesting that evoked synaptic activity is not required. Perfusion with an extracellular solution containing Cd2+ (40 microM), a broad spectrum inhibitor of voltage-dependent Ca2+ channels, or a low concentration (50 microM) of Ni2+, which preferentially blocks T-type, low-voltage-activated Ca2+ channels, also caused a significant decrease in potentiation, whereas an inhibitor of L-type, high voltage-activated Ca2+ channel, nifedipine (20 microM), had no effect. These results suggest that the presence of extracellular Ca2+ during a specific period after high-frequency synaptic activity is necessary for the maintenance of long-term potentiation, and that voltage-gated Ca2+ channels play a role in the stabilization of synaptic plasticity.

Animals↗