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A Araque

Publications and source records attributed to A Araque.

At least 19 recordsLinked to original sources
PubMed2005

Angiotensinase activity is asymmetrically distributed in the amygdala, hippocampus and prefrontal cortex of the rat.

There are important asymmetries in brain functions such as emotional processing and stress response in humans and animals. Knowledge of the bilateral distribution of brain neurotransmitters is important to appropriately understand its functions. Some peptides such as those included in the renin-angiotensin system (RAS) and cholecystokinin (CCK) are related to modulation of behavior and stress. However, although angiotensin AT1 and CCK type 2 receptors were found in adult rat brain, there are no studies of their bilateral distribution in stress-related areas. The function of angiotensin peptides is depending on the action of several aminopeptidases (AP) called angiotensinases, some of them being also involved in the metabolism of CCK. We have studied the bilateral distribution of soluble (SOL) and membrane-bound (MEM) alanyl- (AlaAP), cystinyl- (CysAP), glutamyl- (GluAP) and aspartyl- (AspAP) AP activities in stress-related areas such as amygdala, hippocampus and medial prefrontal cortex of adult male rats in resting conditions. These enzymes are involved in the metabolism of angiotensins (AlaAP, CysAP, GluAP, AspAP) and CCK (GluAP, AspAP). In the amygdala, all the activities studied showed a right predominance with a significant difference ranging from 30% for SOL CysAP to 125% for SOL GluAP. In the hippocampus, there was a left predominance for SOL AlaAP, SOL and MEM CysAP and MEM AspAP activities (100, 80, 300 and 100% higher, respectively). In contrast, GluAP predominated remarkably in the right hippocampus (eight-fold for SOL and three-fold for MEM). In the prefrontal cortex, SOL and MEM CysAP and SOL AspAP predominated in the left hemisphere (40, 100 and 40% higher, respectively). These results demonstrated a heterogeneous bilateral pattern of angiotensinase activities in motivation and stress-related areas. This may reflect an uneven asymmetrical distribution of their endogenous substrates depending on the brain location and consequently, it would be also a reflect of the asymmetries in the functions they are involved in.

Aminopeptidases↗
PubMed2004

Synaptic regulation of the astrocyte calcium signal.

During the last years, a great amount of evidence demonstrates the existence of bidirectional communication between astrocytes and neurons, which has revealed an important active role of astrocytes in the physiology of the nervous system. As a consequence of this evidence, a new concept of the synaptic physiology--"the tripartite synapse"--has been proposed, in which the synapse is formed by three functional elements, i.e., the pre- and postsynaptic elements and the surrounding astrocytes. In this scenario astrocytes play an active role as dynamic regulatory elements in neurotransmission by reciprocally exchanging information with the pre- and postsynaptic elements. The control of the Ca2+ excitability in astrocytes is a key element in this loop of information exchange. In the present article we review and discuss our current knowledge of the properties of the astrocyte intracellular Ca2+ signal and its modulation by the synaptic activity.

Animals↗
PubMed2001

Dynamic signaling between astrocytes and neurons.

Astrocytes, a sub-type of glia in the central nervous system, are dynamic signaling elements that integrate neuronal inputs, exhibit calcium excitability, and can modulate neighboring neurons. Neuronal activity can lead to neurotransmitter-evoked activation of astrocytic receptors, which mobilizes their internal calcium. Elevations in astrocytic calcium in turn trigger the release of chemical transmitters from astrocytes, which can cause sustained modulatory actions on neighboring neurons. Astrocytes, and perisynaptic Schwann cells, by virtue of their intimate association with synapses, are strategically positioned to regulate synaptic transmission. This capability, that has now been demonstrated in several studies, raises the untested possibility that astrocytes are an integral element of the circuitry for synaptic plasticity. Because the highest ratio of glia-to-neurons is found at the top of the phylogenetic tree in the human brain, these recent demonstrations of dynamic bi-directional signaling between astrocytes and neurons leave us with the question as to whether astrocytes are key regulatory elements of higher cortical functions.

Animals↗
PubMed2001

Synaptic regulation of the slow Ca2+-activated K+ current in hippocampal CA1 pyramidal neurons: implication in epileptogenesis.

The slow Ca2+-activated K+ current (sI(AHP)) plays a critical role in regulating neuronal excitability, but its modulation during abnormal bursting activity, as in epilepsy, is unknown. Because synaptic transmission is enhanced during epilepsy, we investigated the synaptically mediated regulation of the sI(AHP) and its control of neuronal excitability during epileptiform activity induced by 4-aminopyridine (4AP) or 4AP+Mg2+-free treatment in rat hippocampal slices. We used electrophysiological and photometric Ca2+ techniques to analyze the sI(AHP) modifications that parallel epileptiform activity. Epileptiform activity was characterized by slow, repetitive, spontaneous depolarizations and action potential bursts and was associated with increased frequency and amplitude of spontaneous excitatory postsynaptic currents and a reduced sI(AHP.) The metabotropic glutamate receptor (mGluR) antagonist (S)-alpha-methyl-4-carboxyphenylglycine did not modify synaptic activity enhancement but did prevent sI(AHP) inhibition and epileptiform discharges. The mGluR-dependent regulation of the sI(AHP) was not caused by modulated intracellular Ca2+ signaling. Histamine, isoproterenol, and (+/-)-1-aminocyclopentane-trans-1,3-dicarboxylic acid reduced the sI(AHP) but did not increase synaptic activity and failed to evoke epileptiform activity. We conclude that 4AP or 4AP+Mg-free-induced enhancement of synaptic activity reduced the sI(AHP) via activation of postsynaptic group I/II mGluRs. The increased excitability caused by the lack of negative feedback provided by the sI(AHP) contributes to epileptiform activity, which requires the cooperative action of increased synaptic activity.

4-Aminopyridine↗
PubMed2001

[Distribution of hepatitis C virus genotypes among the hemodialysis population in the province of Alicante].

UNLABELLED: Hepatitis C virus (HCV) genotypes are irregularly distributed among the different geographic area and groups at risk. OBJECTIVE: To study the different HCV genotypes and subtypes of hemodialyzed patients from Alicante. METHODS: We studied 640 patients on haemodialysis (HD) and we determined the RNA-HCV and the genotypes in the 120 patients with antibodies against HCV (HCV-Ab). We compared the results with the genotypes of 1,370 patients from other groups at risk in the same geographic area. RESULTS: RNA-HCV was not found in the serum in 15% (18/120) of the patients on HD who were HCV-Ab positive. Prevalence of the different genotypes in the 102 patients with positive viral RNA was the following: 1b: 56.8% (58/102), 1a: 19.6% (20/102), 3: 17% (17/102), 2a-2c: 1.9 (2/102), 2b: 0.9% (1/102) 4: 2.9 (3/102), 5: 0.9% (1/102). In conclusion, the genotype 1b was the most frequent in the patients studied in all these areas, and was the same as in the rest of the country. This genotype has been associated with the most severe hepatic disease and poor response to treatment, affecting the prognosis of these patients. The most frequent genotypes in HD in Alicante were 1b, 3 and 1a. HCV genotypes distribution among the HD units was not uniform in the different geographic areas. HCV genotypes distribution in the HD population is similar to other groups at risk from the same geographic area.

Adult↗
PubMed2000

SNARE protein-dependent glutamate release from astrocytes.

We investigated the cellular mechanisms underlying the Ca(2+)-dependent release of glutamate from cultured astrocytes isolated from rat hippocampus. Using Ca(2+) imaging and electrophysiological techniques, we analyzed the effects of disrupting astrocytic vesicle proteins on the ability of astrocytes to release glutamate and to cause neuronal electrophysiological responses, i.e., a slow inward current (SIC) and/or an increase in the frequency of miniature synaptic currents. We found that the Ca(2+)-dependent glutamate release from astrocytes is not caused by the reverse operation of glutamate transporters, because the astrocyte-induced glutamate-mediated responses in neurons were affected neither by inhibitors of glutamate transporters (beta-threo-hydroxyaspartate, dihydrokainate, and L-trans-pyrrolidine-2,4-dicarboxylate) nor by replacement of extracellular sodium with lithium. We show that Ca(2+)-dependent glutamate release from astrocytes requires an electrochemical gradient necessary for glutamate uptake in vesicles, because bafilomycin A(1), a vacuolar-type H(+)-ATPase inhibitor, reduced glutamate release from astrocytes. Injection of astrocytes with the light chain of the neurotoxin Botulinum B that selectively cleaves the vesicle-associated SNARE protein synaptobrevin inhibited the astrocyte-induced glutamate response in neurons. Therefore, the Ca(2+)-dependent glutamate release from astrocytes is a SNARE protein-dependent process that requires the presence of functional vesicle-associated proteins, suggesting that astrocytes store glutamate in vesicles and that it is released through an exocytotic pathway.

ATP-Binding Cassette Transporters↗
PubMed1999

Prostaglandin E(2) stimulates glutamate receptor-dependent astrocyte neuromodulation in cultured hippocampal cells.

Recent Ca(2+) imaging studies in cell culture and in situ have shown that Ca(2+) elevations in astrocytes stimulate glutamate release and increase neuronal Ca(2+) levels, and that this astrocyte-neuron signaling can be stimulated by prostaglandin E(2) (PGE(2)). We investigated the electrophysiological consequences of the PGE(2)-mediated astrocyte-neuron signaling using whole-cell recordings on cultured rat hippocampal cells. Focal application of PGE(2) to astrocytes evoked a Ca(2+) elevation in the stimulated cell by mobilizing internal Ca(2+) stores, which further propagated as a Ca(2+) wave to neighboring astrocytes. Whole-cell recordings from neurons revealed that PGE(2) evoked a slow inward current in neurons adjacent to astrocytes. This neuronal response required the presence of an astrocyte Ca(2+) wave and was mediated through both N-methyl-D-aspartate (NMDA) and non-NMDA glutamate receptors. Taken together with previous studies, these data demonstrate that PGE(2)-evoked Ca(2+) elevations in astrocyte cause the release of glutamate which activates neuronal ionotropic receptors.

2-Amino-5-phosphonovalerate↗
PubMed1999

Tripartite synapses: glia, the unacknowledged partner.

According to the classical view of the nervous system, the numerically superior glial cells have inferior roles in that they provide an ideal environment for neuronal-cell function. However, there is a wave of new information suggesting that glia are intimately involved in the active control of neuronal activity and synaptic neurotransmission. Recent evidence shows that glia respond to neuronal activity with an elevation of their internal Ca2+ concentration, which triggers the release of chemical transmitters from glia themselves and, in turn, causes feedback regulation of neuronal activity and synaptic strength. In view of these new insights, this article suggests that perisynaptic Schwann cells and synaptically associated astrocytes should be viewed as integral modulatory elements of tripartite synapses.

Animals↗
PubMed1999

Fast BK-type channel mediates the Ca(2+)-activated K(+) current in crayfish muscle.

The role of the Ca(2+)-activated K(+) current (I(K(Ca))) in crayfish opener muscle fibers is functionally important because it regulates the graded electrical activity that is characteristic of these fibers. Using the cell-attached and inside-out configurations of the patch-clamp technique, we found three different classes of channels with properties that matched those expected of the three different ionic channels mediating the depolarization-activated macroscopic currents previously described (Ca(2+), K(+), and Ca(2+)-dependent K(+) currents). We investigated the properties of the ionic channels mediating the extremely fast activating and persistent I(K(Ca)). These voltage- and Ca(2+)-activated channels had a mean single-channel conductance of approximately 70 pS and showed a very fast activation. Both the single-channel open probability and the speed of activation increased with depolarization. Both parameters also increased in inside-out patches, i.e., in high Ca(2+) concentration. Intracellular loading with the Ca(2+) chelator bis(2-aminophenoxy) ethane-N, N,N',N'-tetraacetic acid gradually reduced and eventually prevented channel openings. The channels opened at very brief delays after the pulse depolarization onset (<5 ms), and the time-dependent open probability was constant during sustained depolarization (< or =560 ms), matching both the extremely fast activation kinetics and the persistent nature of the macroscopic I(K(Ca)). However, the intrinsic properties of these single channels do not account for the partial apparent inactivation of the macroscopic I(K(Ca)), which probably reflects temporal Ca(2+) variations in the whole muscle fiber. We conclude that the channels mediating I(K(Ca)) in crayfish muscle are voltage- and Ca(2+)-gated BK channels with relatively small conductance. The intrinsic properties of these channels allow them to act as precise Ca(2+) sensors that supply the exact feedback current needed to control the graded electrical activity and therefore the contraction of opener muscle fibers.

Animals↗
PubMed1999

Astrocyte-induced modulation of synaptic transmission.

The idea that astrocytes simply provide structural and trophic support to neurons has been challenged by recent evidence demonstrating that astrocytes exhibit a form of excitability and communication based on intracellular Ca2+ variations and intercellular Ca2+ waves, which can be initiated by neuronal activity. These astrocyte Ca2+ variations have now been shown to induce glutamate-dependent Ca2+ elevations and slow inward currents in neurons. More recently, it has been demonstrated that synaptic transmission between cultured hippocampal neurons can be directly modulated by astrocytes. We have reported that astrocyte stimulation can increase the frequency of miniature synaptic currents. Furthermore, we also have demonstrated that an elevation in the intracellular Ca2+ in astrocytes induces a reduction in both excitatory and inhibitory evoked synaptic transmission through the activation of selective presynaptic metabotropic glutamate receptors.

Animals↗
PubMed1998

Calcium elevation in astrocytes causes an NMDA receptor-dependent increase in the frequency of miniature synaptic currents in cultured hippocampal neurons.

Astrocytes exhibit a form of excitability and communication on the basis of intracellular Ca2+ variations (Cornell-Bell et al., 1990; Charles et al., 1991) that can be initiated by neuronal activity (Dani et al., 1992; Porter and McCarthy, 1996). A Ca2+ elevation in astrocytes induces the release of glutamate (Parpura et al., 1994; Pasti et al., 1997; Araque et al., 1998;Bezzi et al., 1998), which evokes a slow inward current in neurons and modulates action potential-evoked synaptic transmission between cultured hippocampal cells (Araque et al., 1998), suggesting that astrocytes and neurons may function as a network with bidirectional communication. Here we show that a Ca2+ elevation in astrocytes increases the frequency of excitatory as well as inhibitory miniature postsynaptic currents (mPSCs), without modifying their amplitudes. Thapsigargin incubation, microinjection of the Ca2+ chelator BAPTA, and photolysis of the Ca2+ cage NP-EGTA demonstrate that a Ca2+ elevation in astrocytes is both necessary and sufficient to modulate spontaneous transmitter release. This Ca2+-dependent release of glutamate from astrocytes enhances mPSC frequency by acting on NMDA glutamate receptors, because it is antagonized by D-2-amino-5-phosphonopentanoic acid (AP5) or extracellular Mg2+. These NMDA receptors are located extrasynaptically, because blockage specifically of synaptic NMDA receptors by synaptic activation in the presence of the open channel blocker MK-801 did not impair the AP5-sensitive astrocyte-induced increase of mPSC frequency. Therefore, astrocytes modulate spontaneous excitatory and inhibitory synaptic transmission by increasing the probability of transmitter release via the activation of NMDA receptors.

2-Amino-5-phosphonovalerate↗
PubMed1998

Glutamate-dependent astrocyte modulation of synaptic transmission between cultured hippocampal neurons.

The idea that astrocytes merely provide structural and trophic support for neurons has been challenged by the demonstration that astrocytes can regulate neuronal calcium levels. However, the physiological consequences of astrocyte-neuron signalling are unknown. Using mixed cultures of rat hippocampal astrocytes and neurons we have determined functional consequences of elevating astrocyte calcium levels on co-cultured neurons. Electrical or mechanical stimulation of astrocytes to increase their calcium level caused a glutamate-dependent slow inward current (SIC) in associated neurons. Microinjection of 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA) into astrocytes to prevent the stimulus-dependent increase in astrocyte calcium level, blocks the appearance of the neuronal SIC. Pharmacological manipulations indicate that this astrocyte-dependent SIC is mediated by extracellular glutamate acting on N-methyl-D-aspartate (NMDA) and non-NMDA glutamate receptors. Additionally, stimulation of astrocytes reduced the magnitude of action potential-evoked excitatory and inhibitory postsynaptic currents through the activation of metabotropic glutamate receptors. The demonstration that astrocytes modulate neuronal currents and synaptic transmission raises the possibility that astrocytes play a neuromodulatory role by controlling the extracellular level of glutamate.

Animals↗
PubMed1998

Voltage-gated and Ca2+-activated conductances mediating and controlling graded electrical activity in crayfish muscle.

Crayfish opener muscle fibers provide a unique preparation to quantitatively evaluate the relationships between the voltage-gated Ca2+ (ICa) and Ca2+-activated K+ (IK(Ca)) currents underlying the graded action potentials (GAPs) that typify these fibers. ICa, IK(Ca), and the voltage-gated K+ current (IK) were studied using two-electrode voltage-clamp applying voltage commands that simulated the GAPs evoked in current-clamp conditions by 60-ms current pulses. This methodology, unlike traditional voltage-clamp step commands, provides a description of the dynamic aspects of the interaction between different conductances participating in the generation of the natural GAP. The initial depolarizing phase of the GAP was due to activation of the ICa on depolarization above approximately -40 mV. The resulting Ca2+ inflow induced the activation of the fast IK(Ca) (<3 ms), which rapidly repolarized the fiber (<6 ms). Because of its relatively slow activation, the contribution of IK to the GAP repolarization was delayed. During the final steady GAP depolarization ICa and IK(Ca) were simultaneously activated with similar magnitudes, whereas IK aided in the control of the delayed sustained response. The larger GAPs evoked by higher intensity stimulations were due to the increase in ICa. The resulting larger Ca2+ inflow increased IK(Ca), which acted as a negative feedback that precisely controlled the fiber's depolarization. Hence IK(Ca) regulated the Ca2+-inflow needed for the contraction and controlled the depolarization that this Ca2+ inflow would otherwise elicit.

Action Potentials↗
PubMed1997

Sustained GABA-induced regulation of the L-type Ca2+ conductance in crustacean muscle fibers.

The sustained effects of gamma-aminobutyric acid (GABA) on voltage-gated conductances, and excitatory and inhibitory postsynaptic currents (EPSC and IPSC, respectively) in crayfish opener muscle fibers were analyzed using the two-electrode voltage-clamp technique. GABA (1.0 mM) was applied for 1-2 min and measurements were performed 30 min after restoring control Ringer solution. The L-type Ca2+ current (ICa) was reduced by > 33%. The ICa conductance (gCa) was reduced and the activation and inactivation were slowed down by GABA. The ICa regulation outlasted GABA superfusion (150 min). A small decrease (< 19%) of the Ca2+-activated K+ current (IKCa), due to the ICa reduction, was also recorded. The leak (IL), the delayed-rectifier (IK) and the hyperpolarization-activated (IAB) currents were not affected. Picrotoxin (0.5 mM) and bicuculline (0.2 mM) blocked the ICa reduction. Neither the GABAB antagonist saclofen (1.0 mM) nor the agonist baclofen (1.0 mM) had any effect. Therefore, the ICa regulation was probably mediated through GABAA receptors. EPSCs, but not IPSCs, were reduced (30%) for prolonged periods (> 100 min.) after GABA application. We describe a new, potentially functional, role for GABA receptors in the mediation of a sustained reduction of presynaptic and postsynaptic excitability in crustacean muscle.

Animals↗
PubMed1996

Preparative isoelectric focusing and Joule effect: a purification cell that contains a heat exchanger.

Reproducibility in protein purification by preparative isoelectric focusing depends greatly on temperature control during the separation process. A preparative apparatus is described, including a heat exchanger between compartments with isoelectric membranes. The selectivity of the isoelectric membranes was optimized as a function of isoelectric points of the separated proteins. At 2500 V and 60 W, 0.3 g of horse heart myoglobin from 0.2 g of whale skeletal muscle myoglobin could be separated in 1 h. At a total load of 2 g protein, 97% of bovine hemoglobin (2% initial concentration) was purified from bovine serum albumin (0.15%).

Electrochemistry↗
PubMed1996

Lipoprotein(a) and vascular access survival in patients on chronic hemodialysis.

Lipoprotein(a) [Lp(a)] is an independent risk factor for atherosclerotic and cardiovascular complications in the general population and in hemodialysis patients. Increased Lp(a) levels have been also described as a possible predictor of vascular access occlusion in patients on chronic hemodialysis. We have studied prospectively the relationship between vascular access survival and Lp(a) levels in 40 hemodialysis patients. The Lp(a) plasma concentrations were measured by enzyme-linked immunosorbent assay in all patients in April 1993. Throughout the following year, evolution and survival of their vascular accesses were analyzed. Failure of vascular access was established when there were complications requiring surgical repair or transluminal angioplasty. Fourteen patients showed failure of vascular access, and the cumulative survival of vascular accesses after 1 year of follow-up was 63.8%. The Lp(a) levels were higher in patients with failure of vascular access than in the others (35.2 +/- 31 vs. 22.4 +/- 25 md/dl), but this difference did not reach statistical significance (p = 0.064). The vascular access survival in patients with Lp(a) levels > 75th percentile (52.5 mg/dl) was significantly lower than in the remaining patients (40 vs. 72%; p = 0.045). This difference increased when we analyzed the patients with Lp(a) levels > 90th percentile (76 md/dl; 25 vs. 68%; p = 0.002). Our results suggest that patients with the highest levels of Lp(a) are at risk of developing complications in their vascular accesses, and they also have lower vascular access survival.

Adult↗