Direct solid sampling for speciation of Zn2+ and ZnO nanoparticles in cosmetics by graphite furnace atomic absorption spectrometry.

The application of nanoparticles (NPs) in science and technology is a fast growing field. Therefore, reliable and straightforward analytical methods are required for their fast determination in different types of samples. This work investigates a method that enables the determination of ZnO NPs, discriminating them from ionic zinc in cosmetic samples. The method is based on direct solid sampling high-resolution continuum source electrothermal atomic absorption spectrometry (SS-HR-CS-GFAAS), and has been applied to determination of ZnO NPs, Zn2+ and total Zn in eye shadow samples. In this work the deconvolution of the atomization peak and the calibration by standard additions have been done in order to discriminate and quantify ionic zinc and ZnO NPs. A Zn wavelength with low sensitivity was selected. The proper optimization of the graphite furnace temperature program, minimizing the mineralization of the sample matrix, enables different atomization profiles between the different chemical species of the analyte. Two multiple response surface designs have been used in order to optimize the adequate furnace program to achieve our aims. All the optimization experiments were performed using a sample of eye shadow. Further, a method for the determination of total Zn by direct solid sampling with calibration by aqueous standards, was also optimized. The optimized method was successfully applied to the determination of ionic Zn and ZnO NPs in different eye shadow samples, and has been validated by recovery assays, obtaining recovery percentages between 80 and 125%. Total Zn concentration in the solid samples was validated by the determination of total Zn by direct solid sampling and by the analysis of the same eye shadow samples digested in microwave oven.

NMDA Receptors Containing GluN2B/2C/2D Subunits Mediate an Increase in Glutamate Release at Hippocampal CA3-CA1 Synapses.

NMDA receptors (NMDARs) are involved in synaptic transmission and synaptic plasticity in different brain regions, and they modulate glutamate release at different presynaptic sites. Here, we studied whether non-postsynaptic NMDARs, putatively presynaptic (preNMDARs), are tonically active at hippocampal CA3-CA1 synapses, and if they modulate glutamate release. We found that when postsynaptic NMDARs are blocked by MK801, D-AP5 depresses evoked and spontaneous excitatory synaptic transmission, indicating that preNMDARs are tonically active at CA3-CA1 synapses, facilitating glutamate release. The subunit composition of these NMDARs was determined by studying evoked and spontaneous excitatory synaptic transmission in the presence of Zn2+, Ro 25-6981, and PPDA, antagonists of NMDARs containing GluN2A, GluN2B, and GluN2C/D, respectively. We found that evoked and spontaneous release decreased when the activity of NMDARs containing GluN2B and GluN2C/D subunits but not GluN2A was impeded. In addition, we found that the increase in glutamate release mediated by these NMDARs requires protein kinase A (PKA) activation. We conclude that preNMDARs that contain GluN2B and GluN2C/2D subunits facilitate glutamate release at hippocampal CA3-CA1 synapses through a mechanism that involves PKA.

No Evidence of Dengue Virus Infections in Several Species of Bats Captured in Central and Southern Mexico.

Bats are reservoirs for viruses with zoonotic potential in the Americas, and scattered evidence exists suggesting that bats may act as reservoirs for dengue virus (DENV). To explore further the role of bats as part of DENV sylvatic cycles, 240 bats of 18 species were captured in 2 states of Mexico with contrasting ecological characteristics but concurrent DENV activity in humans. RT-PCR analysis of RNA extracted from liver or spleen tissue from de bats failed to show evidence for the presence of DENV nucleic acids in these organs. In addition, plasma assayed by plaque reduction neutralization test showed no evidence of neutralizing anti-DENV antibodies. These results suggest that American bats may not be reservoirs or amplification host for DENV infection.

Stabilization of apoptotic cells: generation of zombie cells.

Apoptosis is characterized by degradation of cell components but plasma membrane remains intact. Apoptotic microtubule network (AMN) is organized during apoptosis forming a cortical structure beneath plasma membrane that maintains plasma membrane integrity. Apoptotic cells are also characterized by high reactive oxygen species (ROS) production that can be potentially harmful for the cell. The aim of this study was to develop a method that allows stabilizing apoptotic cells for diagnostic and therapeutic applications. By using a cocktail composed of taxol (a microtubule stabilizer), Zn(2+) (a caspase inhibitor) and coenzyme Q10 (a lipid antioxidant), we were able to stabilize H460 apoptotic cells in cell cultures for at least 72 h, preventing secondary necrosis. Stabilized apoptotic cells maintain many apoptotic cell characteristics such as the presence of apoptotic microtubules, plasma membrane integrity, low intracellular calcium levels and mitochondrial polarization. Apoptotic cell stabilization may open new avenues in apoptosis detection and therapy.

Neonatal olfactory bulbectomy enhances locomotor activity, exploratory behavior and binding of NMDA receptors in pre-pubertal rats.

In this study, we investigated the effect of neonatal olfactory bulbectomy (nOBX) on behavioral paradigms related to olfaction such as exploratory behavior, locomotor activity in a novel environment and social interaction. We also studied the effect of nOBX on the activity of the N-methyl-d-aspartate (NMDA) subtype of glutamate receptors during development. The behavioral effects of nOBX (postnatal day 7, PD7) were investigated in pre- (PD30) and post-pubertal (PD60) Wistar rats. NMDA receptor activity was measured with [(125)I]MK-801 in the brain regions associated with the olfactory circuitry. A significant increase in the novelty-induced locomotion was seen in the pre-pubertal nOBX rats. Although the locomotor effect was less marked than in pre-pubertal rats, the nOBX rats tested post-pubertally failed to habituate to the novel situation as quickly as the sham- and normal- controls. Pre-pubertally, the head-dipping behavior was enhanced in nOBX rats compared with sham-operated and normal controls, while normal exploratory behavior was observed between groups in adulthood. In contrast, social interaction was increased in post-pubertal animals that underwent nOBX. Both pre- and post-pubertal nOBX rats recovered olfaction. Interestingly, pre-pubertal rats showed a significant increase in the [(125)I]MK-801 binding in the piriform cortex, dorsal hippocampus, inner and outer layers of the frontal cortex and outer layer of the cingulate cortex. At post-pubertal age, no significant differences in [(125)I]MK-801 binding were observed between groups at any of the brain regions analyzed. These results suggest that nOBX produces pre-pubertal behavioral disturbances and NMDA receptor changes that are transitory with recovery of olfaction early in adulthood.

Dendritic morphology changes in neurons from the prefrontal cortex, hippocampus and nucleus accumbens in rats after lesion of the thalamic reticular nucleus.

Several studies in rodents have shown that dysfunctions of the thalamic reticular nucleus (TRN) result in deficits of sensory gating and attentional processes, two core features of schizophrenia. TRN receives inputs from the prefrontal cortex (PFC) and hippocampal formation, two structures which send excitatory projections to the nucleus accumbens (NAcc) and are interconnected with the basolateral amygdala (BLA). Here we determined whether (and which) changes occurred four weeks after a TRN lesion in the dendritic morphology of pyramidal neurons of layers 3 and 5 of the PFC, neurons of ventral and dorsal hippocampus, BLA, and the medium spiny neurons of the NAcc. Dendritic morphology and characteristics were measured by using Golgi-Cox procedure followed by Sholl analysis. We also evaluated the effects of TRN lesion on exploratory behavior assessed by hole-board test and locomotor activity induced by a novel environment. We found that TRN damage induced a reduction in the exploratory behavior measured by hole-board test with neuronal hypotrophy in PFC (layer 5), CA1 ventral hippocampus and NAcc neurons. Taken together, these data suggest that the behavioral and morphological effects of TRN lesion are, at least partially, mediated by limbic subregions with possible consequences for schizophrenia-related behaviors.

Mieloma múltiple IgDlambda con fracaso renal agudo. A propósito de un caso / No disponible

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Sirolimus and everolimus induced pneumonitis in adult renal allograft recipients: experience in a center.

Mammalian target of rapamycin (mTOR) inhibitors induce pneumonitis, an unusual but potentially fatal side effect of this drug group. We retrospectively collected the cases of pneumonitis induced by sirolimus or everolimus among 1471 adult cadaveric renal transplant recipients who were grafted at our institution from 1980-2008. Due to chronic transplant dysfunction or tumor, 205 patients were switched from calcineurin inhibitors to sirolimus (n = 88) or to everolimus (n = 117). Six patients (2.9%) developed pneumonitis: 1 was associated with sirolimus and 5 with everolimus (5 males and 1 female; median age, 60 years [range, 47-73 years]). Median times from conversion to pneumonitis onset were 34 days in 4 patients (range, 24-46 days) and 491 days in 2 subjects (range, 454-528 days). The mean drug trough level at presentation was 8.2 microg/L (range, 5.5-13.8 microg/L). The most common symptoms were dry cough (n = 6), fever (n = 5), and dyspnea (n = 4). Imaging tests revealed lower lobe involvement in all patients. Bronchoalveolar lavage performed in 4 patients showed lymphocytic alveolitis. All patients completely recovered after drug withdrawal. Five patients received steroids, 5 were switched to a calcineurin inhibitor, and 1 was switched to the other mTOR inhibitor. In conclusion, mTOR inhibitor-associated pneumonitis is a rare disease. Sirolimus did not cause more cases of pneumonitis than everolimus. Pneumonitis development was not dependent upon the drug blood level. Lower lobe involvement and lymphocytic alveolitis were usually present. Discontinuation of the mTOR inhibitor with steroid prescription resulted in adequate outcomes. A change to the other mTOR inhibitor should be contemplated if patient circumstances require this type of immunosuppression.

Kainate receptor-mediated presynaptic inhibition converges with presynaptic inhibition mediated by Group II mGluRs and long-term depression at the hippocampal mossy fiber-CA3 synapse.

Kainate receptors (KARs) effect depression of glutamate release at hippocampal mossy fiber-CA3 (MF-CA3) synapses by a metabotropic action involving adenylyl cyclase (AC) inhibition, cAMP reduction, and diminished protein kinase A (PKA) activation. Using hippocampal slices, we show here that KAR activation interferes with the depression of glutamate release produced by Group II metabotropic glutamate receptor stimulation and low frequency stimulation (LFS)-induced long-term depression (LTD), also expressed through presynaptic AC/cAMP/PKA at MF-CA3 synapses. The mutual occlusion of depression mediated by presynaptic KARs, Group II mGluR and LFS-induced LTD suggests their mechanistic convergence at the MF-CA3 synapse and thus invokes KARs in synaptic plasticity manifest in LTD.

Varicella infection in adult renal allograft recipients: experience at one center.

Disseminated varicella-zoster virus (VZV) infection in adult renal allograft recipients is a rare but potentially fatal illness. We retrospectively collected the cases of VZV infection that occurred in 812 adult renal transplant recipients, performed between 1995 and 2004 at our institution. Eight patients developed varicella (1%), seven men and one woman. The overall median age was 38 years (range = 31 to 64). The median time from transplantation to infection was 32 months (range = 2 to 92). Four cases were primary infections and four disseminated VZV reactivations. Immunosuppression consisted of prednisone (PDN) + cyclosporine (CSA) + mycophenolate (MF; n = 4); PDN + CSA + azathioprine (n = 1); PDN + tacrolimus (FK) + MF (n = 1); FK + MF (n = 1); PDN + rapamycin + MF (n = 1). Seven patients (87%) required hospital admission for a median duration of 11 days (range = 3 to 21). Four patients were previously diagnosed with chronic hepatitis virus infection: two type B (HBV) and two type C (HCV). The last cohort required longer admission than the negative patients (11.5 +/- 3 vs 7.5 +/- 9 days; P = .1). The only clinical manifestation in four patients was general malaise, fever, and a disseminated vesicular rash; the other four patients also showed visceral involvement: two pneumonitis, one hepatitis, and thrombotic microangiopathy, and one developed multiorgan failure and died due to a delayed diagnosis in a patient positive for HBVs. The diagnosis was established according to the symptoms, IgG-IgM seroconversion and VZV polymerase chain reaction quantification in vesicle contents. Treatment consisted of reduced immunosuppression, antiviral drugs (acyclovir or gancyclovir), and in six patients, a varicella-zoster immunoglobulin dose. We concluded that varicella infection in adult renal allograft recipients is unusual but highly morbid. A vaccination program in seronegative pretransplant candidates should be attempted. Early diagnosis and treatment may improve the prognosis. Although further studies are required, chronic HBV or HCV infection seemed to be a risk factor for the disease.

Receptores de glutamato de tipo kainato y epilepsia / Kainate-type glutamate receptors and epilepsy

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[The role of kainate receptors in the regulation of excitatory synaptic transmission in the hippocampus]. / Función de los receptores de kainato en la regulación de la transmisión sináptica excitadora en el hipocampo.

AIMS: To describe the state of the art with regard to the physiology of kainate-like glutamate receptors as modulators in glutamatergic excitatory synaptic transmission in the hippocampus. DEVELOPMENT: Kainate receptors modulate the release of glutamate in the hippocampus in the different synapses that have been studied to date. Their activation can produce a decrease or an increase in glutamate release according to the synapse under study and both types of modulation (increase or decrease) can take place even within the same synaptic connection, depending on the agonist concentration reached by the receptors. Thus, in the synapses that are established among the mossy fibres and the pyramidal neurones in region CA3, high concentrations (> 100 nM) of kainate trigger a drop in glutamate release, whereas low concentrations (< 50 nM) give rise to an increased release of the same neurotransmitter. These actions carried out by the kainate receptors are presynaptic and both ionotropic and metabotropic mechanisms have been proposed to explain them. CONCLUSIONS: Kainate receptors act in the hippocampus as modulators of glutamate release, by either increasing or decreasing it. They therefore help to keep the balance of neuronal excitability, also play a part in neuronal plasticity processes (LTP and LTD) and can trigger, under abnormal conditions, a notable imbalance of this excitability and give rise to epileptic-type firing patterns, among other disorders.

Función de los receptores de kainato en la regulación de la transmisión sináptica excitadora en el hipocampo / The role of kainate receptors in the regulation of excitatory synaptic transmission in the hippocampus

Objetivo. Describir el estado actual de conocimientos sobre la fisiología de los receptores de glutamato de tipo kainato como moduladores de la transmisión sináptica excitadora glutamatérgica en el hipocampo. Desarrollo. Los receptores de kainato modulan la liberación de glutamato en el hipocampo en las distintas sinapsis estudiadas hasta el momento. Su activación puede producir una disminución o un aumento de la liberación de glutamato en función de la sinapsis estudiada e incluso dentro de la misma conexión sináptica pueden dar lugar a ambos tipos de modulación (aumento o disminución), dependiendo de la concentración de agonista que alcanza a los receptores. Así, en la sinapsis establecida entre las fibras musgosas y las neuronas piramidales de la región CA3, concentraciones elevadas (> 100 nM) de kainato producen una disminución de la liberación de glutamato, mientras que concentraciones pequeñas (< 50 nM) producen un incremento de la liberación del mismo neurotransmisor. Estas acciones de los receptores de kainato son presinápticas y para ellas se han propuesto mecanismos tanto ionotrópicos como metabotrópicos. Conclusiones. Los receptores de kainato actúan en el hipocampo como moduladores de la liberación de glutamato, aumentándola o disminuyéndola; contribuyen así al mantenimiento del equilibrio de la excitabilidad neuronal, participan además en procesos de plasticidad neuronal (LTP y LTD) y pueden producir, en condiciones anormales, un marcado desequilibrio de esta excitabilidad y dar lugar, entre otras alteraciones, a patrones de disparo de tipo epiléptico (AU)

Aims. To describe the state of the art with regard to the physiology of kainate-like glutamate receptors as modulators in glutamatergic excitatory synaptic transmission in the hippocampus. Development. Kainate receptors modulate the release of glutamate in the hippocampus in the different synapses that have been studied to date. Their activation can produce a decrease or an increase in glutamate release according to the synapse under study and both types of modulation (increase or decrease) can take place even within the same synaptic connection, depending on the agonist concentration reached by the receptors. Thus, in the synapses that are established among the mossy fibres and the pyramidal neurones in region CA3, high concentrations (> 100 nM) of kainate trigger a drop in glutamate release, whereas low concentrations (< 50 nM) give rise to an increased release of the same neurotransmitter. These actions carried out by the kainate receptors are presynaptic and both ionotropic and metabotropic mechanisms have been proposed to explain them. Conclusions. Kainate receptors act in the hippocampus as modulators of glutamate release, by either increasing or decreasing it. They therefore help to keep the balance of neuronal excitability, also play a part in neuronal plasticity processes (LTP and LTD) and can trigger, under abnormal conditions, a notable imbalance of this excitability and give rise to epileptic-type firing patterns, among other disorders (AU)

Association of the genetic polymorphisms of the renin-angiotensin system with kidney graft long-term outcome: preliminary results.

Recent studies have demonstrated some association between the renin-angiotensin system (RAS) activity and the development and progression of different entities as diabetes mellitus (DM) or chronic allograft nephropathy. To investigate these associations, we studied some gene polymorphisms of RAS in a group of renal transplant recipients. We retrospectively analyzed 42 patients who underwent a primary renal transplantation for 2 years. A subgroup of 23 patients (55%) was diagnosed with postransplant DM in accordance with American Diabetes Association 2001 criteria. We studied two RAS gene polymorphisms: the angiotensin-converting enzyme insertion/deletion (ACE I/D) and angiotensinogen (AGTM235T). Genotyping was performed by DNA purification and amplification with a polymerase chain reaction technique. The distributions of genotypes were ACE DD, ID, II: 33%, 48%, 19%; and AGT TT, MT, MM: 15%, 45%, 40%, respectively. We observed a progressive loss in renal function measured by creatinine clearance (Cockroft) in D-allele carriers (DD+ID) between the first and the second transplantation year: 65.3 +/- 4.3 vs 59.8 +/- 4.6 mL/min (P = 0.02); that was not seen in II patients: 68.8 +/- 4.6 vs 68.4 +/- 4 mL/min (P = 0.87). Fifty percent of D-allele carriers developed DM vs 25% of non-D-allele carriers (P = 0.19). Eighty-three percent of homozygous patients for the AGT-TT allele developed DM vs 35% of non TT patients (P = 0.04). There were no significant differences regarding recipient demographic characteristics, type of donor, number and severity of acute rejections, and immunosuppressant treatment between the groups. In conclusion, ACE D-allele seems to be associated with a poorer kidney graft long-term outcome. ACE D and AGT T alleles may be implicated in glucose metabolism disorders after transplantation.

Receptores de kainato. Función en la regulación de la transmisión sináptica gabérgica en el hipocampo / Kainate receptors. Their function in the regulation of gabaergic synaptic transmission in the hippocampus

Objetivo. Describir el estado actual de conocimientos sobre la fisiología de los receptores de glutamato de tipo kainato como moduladores de la transmisión sináptica inhibidora gabérgica en el hipocampo. Desarrollo. En la sinapsis interneurona-célula principal de la capa CA1 del hipocampo, se produce una depresión de la transmisión sináptica inhibidora gabérgica por la activación de receptores de kainato situados en el terminal presináptico de las interneuronas. Esta disminución de la liberación de GABA involucra una acción metabotrópica, demanera que requiere la activación de una proteína G sensible a la toxina pertúsica y la activación de la proteína cinasa C. En estas mismas interneuronas, también existe una población de receptores de kainato de acción ionotrópica en el compartimento somatodendrítico cuya activación las despolariza y produce una liberación masiva de neurotransmisor. Muy recientemente, se ha demostrado que la activación de receptores de kainato por concentraciones submicromolares de agonista puede producir un aumento de la liberación de GABA. Este efecto se ha descrito sobre todo en las sinapsis interneurona-interneurona, si bien el mecanismo de acción de los receptores de kainato para producir este efecto aún no se ha descrito. Conclusiones. Los receptores de kainato actúan en el hipocampo como moduladores de la liberación de GABA, inhibiéndola o incrementándola, de modo que contribuyen al mantenimiento del exquisito equilibrio de la excitabilidad neuronal. En condiciones anormales pueden producir un marcado desequilibrio de esta excitabilidad y dar lugar, entre otras alteraciones, a patrones de disparo de tipo epiléptico (AU)

Aims. The aim of this study is to describe the current state of knowledge about the physiology of kainate-type glutamate receptors as modulators of GABAergic synaptic transmission in the hippocampus. Development. The activation of kainate receptors (KR) located in the presynaptic terminal of the interneurons reduces GABAergic synaptic transmission at the interneuron-principal cell synapse in the CA1 layer of the hippocampus. This diminished release of GABA involves a metabotropic effect, and an that activation of both a pertussis toxin-sensitive G-protein and protein kinase C is required. In these same interneurons there is also a population of KR with an ionotropic effect in the somatodendritic compartment, which depolarise them and give rise to a massive release of neurotransmitter when activated. It has very recently been shown that activating KR by submicromolar concentrations of agonist can bring about an increase in the release of GABA, an effect described principally in the interneuroninterneuron synapses, although the mechanism by which the KR produce this effect is yet to be described. Conclusions. KR act in the hippocampus as modulators of GABA release; they increase or decrease it and hence play a part in maintaining the exquisite balance of neuronal excitability. In abnormal conditions they can also notably upset the balance of this excitability and give rise to firing patterns of an epileptic kind, among other disorders (AU)

[Kainate receptors. Their function in the regulation of GABAergic synaptic transmission in the hippocampus]. / Receptores de kainato. Función en la regulación de la transmisión sináptica gabérgica en el hipocampo.

AIMS: The aim of this study is to describe the current state of knowledge about the physiology of kainate type glutamate receptors as modulators of GABAergic synaptic transmission in the hippocampus. DEVELOPMENT: The activation of kainate receptors (KR) located in the presynaptic terminal of the interneurons reduces GABAergic synaptic transmission at the interneuron principal cell synapse in the CA1 layer of the hippocampus. This diminished release of GABA involves a metabotropic effect, and an that activation of both a pertussis toxin sensitive G protein and protein kinase C is required. In these same interneurons there is also a population of KR with an ionotropic effect in the somatodendritic compartment, which depolarise them and give rise to a massive release of neurotransmitter when activated. It has very recently been shown that activating KR by submicromolar concentrations of agonist can bring about an increase in the release of GABA, an effect described principally in the interneuron interneuron synapses, although the mechanism by which the KR produce this effect is yet to be described. CONCLUSIONS: KR act in the hippocampus as modulators of GABA release; they increase or decrease it and hence play a part in maintaining the exquisite balance of neuronal excitability. In abnormal conditions they can also notably upset the balance of this excitability and give rise to firing patterns of an epileptic kind, among other disorders.

Molecular physiology of kainate receptors.

A decade ago, our understanding of the molecular properties of kainate receptors and their involvement in synaptic physiology was essentially null. A plethora of recent studies has altered this situation profoundly such that kainate receptors are now regarded as key players in the modulation of transmitter release, as important mediators of the postsynaptic actions of glutamate, and as possible targets for the development of antiepileptic and analgesic drugs. In this review, we summarize our current knowledge of the properties of kainate receptors focusing on four key issues: 1) their structural and biophysical features, 2) the important progress in their pharmacological characterization, 3) their pre- and postsynaptic mechanisms of action, and 4) their involvement in a series of physiological and pathological processes. Finally, although significant progress has been made toward the elucidation of their importance for brain function, kainate receptors remain largely an enigma and, therefore, we propose some new roads that should be explored to obtain a deeper understanding of this young, but intriguing, class of proteins.

Two populations of kainate receptors with separate signaling mechanisms in hippocampal interneurons.

Consistent with the epileptogenic and deleterious effects of the potent neurotoxin kainate, the activation of kainate receptors reduces the synaptic inhibition induced by the amino acid gamma-aminobutyric acid (GABA). Extrapolating from these data led to the conclusion that kainate receptors are located presynaptically. However, kainate directly depolarizes the inhibitory interneurons, causing them to fire repeatedly. This effect might indirectly decrease the size of inhibitory postsynaptic currents recorded from pyramidal cells and places in doubt the presynaptic location for kainate receptors. Here we show that both effects, membrane depolarization and the reduction of inhibitory potentials, can be dissociated by several means, particularly by the natural agonist of kainate receptors, glutamate. Indeed, when applied at low concentrations, glutamate inhibited GABA release without affecting the firing rate of GABA interneurons. These results indicate that CA1 interneurons contain two populations of kainate receptors, each with different agonist sensitivity and coupled to distinct signaling pathways.

Activation and desensitization properties of native and recombinant kainate receptors.

The activation-inactivation properties of membrane currents induced by the rapid application of glutamate or kainate were studied in cultured hippocampal neurons and in HEK cells transfected with a cDNA encoding the GluR6 subunit. The onset of desensitization was rapid and similar in native and recombinant channels (approximately 80 s(-1) of onset rate constant). Recovery from desensitization was slow and agonist-dependent in neurons, proceeding slightly faster in GluR6 receptors. Half-maximal activation (EC50) of native channels was obtained at a glutamate concentration of 330 microM, while the half-maximal steady state desensitization (IC1/2) was attained at 2.8 microM. These values differed from those obtained in recombinant receptors (EC50 = 762 microM and IC1/2 = 0.44 microM). A small window under the crossing point of activation and inactivation curves was observed, indicating that, for some concentrations of either agonist, steady state channel activity could exist. In native receptors, this window presented maximum values at approximately 100 microM for glutamate, which predicted well the potency of glutamate to reduce the GABAergic drive in hippocampal slices. These data indicate that for neuronal kainate receptors, the concentrations for half activation and half inactivation differ by two orders of magnitude such that the maximum response to a maintained concentration of glutamate is small, and the steady state dose response curve is skewed and bell shaped.