Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.6.1.3 (ATPase)
65,361 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ca2+ release from inositol 1,4,5-trisphosphate (IP3)-sensitive and ryanodine-sensitive intracellular Ca2+ stores is mediated by distinct proteins identified as IP3 receptors (IP3R) and ryanodine receptors (RyR), respectively. We have compared the immunohistochemical localizations of IP3R and RyR in the brain at the light and electron microscopic levels and have also evaluated the distribution of the major brain intracellular Ca(2+)-pumping ATPase. IP3R and RyR occur in overlapping populations of neurons in widespread areas of the brain, but labeling is distinct in a number of areas. For example, IP3R is enriched in cerebellar Purkinje cells and hippocampal CA1 pyramidal cells, while RyR is present at relatively low levels in these cells. RyR is most enriched in the dentate gyrus and CA3/4 areas of the hippocampus, where IP3R levels are low. In the cortex, IP3R is found in pyramidal cell bodies and proximal dendrites, whereas RyR is located predominantly in long, thin apical dendrites of pyramidal cells. In deep cerebellar nuclei, RyR is located in cell bodies that appear devoid of IP3R, whereas IP3R is enriched in terminals surrounding cell bodies. Electron microscopy in the hippocampus reveals RyR in axons, dendritic spines, and dendritic shafts near dendritic spines while IP3R is primarily identified in dendritic shafts and cell bodies. These results suggest that the IP3- and ryanodine-sensitive Ca2+ pools have largely distinct roles in controlling intracellular Ca2+ levels, though in some sites they may interact to varying degrees.
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PMID:Differential immunohistochemical localization of inositol 1,4,5-trisphosphate- and ryanodine-sensitive Ca2+ release channels in rat brain. 839 39

Transient changes in extracellular potassium concentration ([K+]o) and field potentials were evoked by 4-aminopyridine (4-AP; 50-100 microM) and recorded with ion-selective microelectrodes in CA1b, CA3b and dentate sectors of adult rat hippocampal slices. Long-lasting field potentials recurred at a frequency of approximately 1/60 s (0.016 +/- 0.003 Hz) in association with increases in [K+]o which were largest and most sustained in the dendritic regions where afferent fibers terminate (dentate > CA1 > CA3) and in the hilus. In stratum radiatum of CA1 or stratum moleculare of the dentate these fields had a peak amplitude of 1.4 +/- 0.29 mV, duration 8.3 +/- 1.6 s, and were accompanied by increases in [K+]o of 1.8 +/- 0.22 mM that lasted 32 +/- 5.5 s (n = 17 slices). Interictal epilentiform potentials, which were brief (< 0.2 s) and more frequent at approximately 1/3 s (0.30 +/- 0.02Hz) were also present in CA1, CA3 and the hilus and associated with small increases in [K+]o (< or = 0.5 mM, duration < or = 2 s). Interictal activity was blocked by 6-cyano-7-nitroquinoxalone-2,3-dione (CNQX; 5-20 microM); the slow, less frequent potentials were resistant to both CNQX and DL-2-amino-5-phosphonovaleric acid (APV; 50 microM) and reversibly blocked (or attenuated by approximately 80%) by bicuculline methiodide (BMI) (25-100 microM). The BMI-sensitive potentials were also abolished by baclofen (100 microM), an effect which was reversed by 2-OH-saclofen (100 microM). Focal application of KCI or GABA in the absence of 4-AP evoked long-lasting field and [K+]o potentials which were similar to those evoked by 4-AP but more sustained. The proportional relationship between the amplitudes of field and K+ potentials with GABA closely resembled that observed for 4-AP; in contrast the slope of KC1-evoked responses was lower. Our results demonstrate that in the adult rat hippocampus 4-AP induces in many different regions accumulations of [K+]o in synchrony with the long-lasting field potentials, which are known to correspond to an intracellular long-lasting depolarization of the pyramidal cells. These changes are smaller than those which occur in the immature rat hippocampus--which may be related to differences in Na-K-ATPase and susceptibility to seizures. These events involve the activation of GABAA receptors, are under the modulatory control of GABAB receptors, and likely arise from the activity of GABAergic interneuron and/or afferent terminals. The long-lasting field potentials appear to reflect mainly the direct depolarizing actions of GABA and to much more limited extent the associated accumulation of [K+]o.
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PMID:Extracellular K+ accumulations and synchronous GABA-mediated potentials evoked by 4-aminopyridine in the adult rat hippocampus. 874 Feb 10

Menkes gene (Mc1 or MNK, encoding putative copper-transporting ATPase) expression was investigated and compared in normal and macular mutant mouse brain. Northern blot analysis showed a distinct 8.3-kb transcript and no obvious difference in size or extent in normal mice and macular mutants on postnatal days 0, 4, 7, 10 or 13. In situ hybridization revealed that certain specific populations of cells in the brain express Menkes mRNA, and that their localization in normal and mutant mice did not differ and was conserved on days 4, 10 and 13. The most intense hybridization signals were observed in the hippocampal CA1 region and dentate gyrus, the olfactory bulb nuclei, the cerebellar granular cell layer, the choroid plexus and the ependyma, with less intense signals in the hippocampal CA3 region and cerebellar Purkinje cells. In addition, necrotic neuronal cell death was predominantly observed in the CA3 region and the Purkinje cells of macular mice after postnatal day 10. The finding that the regions that had lower expression level of Menkes mRNA corresponded to those showing neuronal necrosis suggests that the Menkes gene may be responsible for the neuronal degeneration in some specific portions of the brain and clinical manifestations in this mutant.
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PMID:Localization of Menkes gene expression in the mouse brain; its association with neurological manifestations in Menkes model mice. 874 Feb 28

Hippocampal CA1 neurons exposed to a nonlethal period (2 min) of ischemia, acquired tolerance to a subsequent lethal 5-min period of ischemia, which usually causes delayed-type neuronal death. Intracellular Ca2+ movements before and after the 5 min of forebrain ischemia were evaluated in gerbil hippocampal CA1 pyramidal neurons, had acquired tolerance in comparison with nonischemia-tolerant CA1 neurons. Evaluation was performed by observing the ultrastructural intracellular Ca2+ distribution and the Ca2+ adenosine triphosphatase (Ca(2+)-ATPase) activity using electron microscopic cytochemistry. In comparison with nonischemia-tolerant CA1 neurons, mitochondria of ischemia-tolerant CA1 neurons sequestered more Ca2+ from the cytosomal fraction 15 min after the 5-min period of ischemia, and Ca2+ deposits in these mitochondria were rapidly decreased. Plasma membrane Ca(2+)-ATPase activities were already significantly elevated before the 5 min of ischemia, and remained at a higher level subsequently compared to nonischemia-tolerant CA1 neurons. Changes in the mitochondrial Ca2+ distribution and Ca(2+)-ATPase activities in ischemia-tolerant CA1 neurons after the 5-min period of ischemia showed a strong resemblance to those in CA3 neurons, which originally possess resistance to such periods of ischemia. These findings suggest that enhanced or maintained activities of mitochondrial Ca2+ sequenstration and plasma membrane Ca(2+)-ATPase reduced Ca2+ toxicity following 5-min ischemia in terms of time, resulting in escape from delayed neuronal death.
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PMID:Calcium movement in ischemia-tolerant hippocampal CA1 neurons after transient forebrain ischemia in gerbils. 878 35

1. Ca2+ imaging and simultaneous intracellular recording were performed on CA3 pyramidal neurons in hippocampal slice cultures and standard acute slices. Both fura-2 and a dextran conjugate of fura-2 (MW = 10,000) were used in the Ca2+ measurements to control for compartmentalization artifacts. Experiments were performed under conditions giving minimal ligand- and voltagegated Ca2+ influx, with the use of competitive and noncompetitive antagonists of ionotropic glutamate receptors and steady-state depolarization, respectively. 2. Tetanic stimulation of stratum lucidum evoked dendritic Ca2+ transients with rapid onset that were blocked by the noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, MK-801 (2-5 microM), but not by the competitive alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) (10-50 microM). Zn(2+)-containing mossy fiber terminals (assessed by Timm's staining) and postsynaptic structures (thorny excrescences) are preserved in s. lucidum of hippocampal slice cultures. 3. A Ca2+ store loading protocol, consisting of brief repolarizations followed by steady depolarization, primed most of the neurons so that a subsequent tetanus gave a Ca2+ increase in the presence of MK-801 that was reported by both fura-2 and the dextran conjugate. The onset of the Ca2+ increase was significantly delayed (by 2-3 s) with respect to the MK-801-sensitive increase, and often had a different spatial pattern within the neuron. Response characteristics were similar in slice cultures and acute slices. 4. The delayed Ca2+ increase showed a steep rundown with subsequent stimuli, but was restored by further priming by the Ca2+ store loading paradigm. Postsynaptic currents evoked by the tetani under these conditions were not correlated with the magnitude of the delayed Ca2+ transients. 5. Delayed Ca2+ increases were observed in 44% of the neurons dialyzed with normal intracellular solution at room temperature. The success rate of observing delayed Ca2+ transients was increased to 86% in neurons maintained at 30 degrees C, and dialyzed with an inhibitor of the inositol-triphosphate-3-kinase. 6. The delayed Ca2+ transients could not be initiated after inhibition of endosomal Ca(2+)-ATPase-mediated uptake by thapsigargin. 7. Both fura-2 and the dextran conjugate reported increases in resting Ca2+ levels after the loading protocols, that were absent after priming in thapsigargin, and decreases in resting Ca2+ levels after successive tetani in MK-801, suggesting that the Ca2+ changes were largely cytosolic. 8. The present results support the hypothesis that these synaptically mediated, delayed Ca2+ transients represent release from intracellular Ca2+ stores that can be loaded and depleted repeatedly, and are evoked by presynaptic release of endogenous neurotransmitter.
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PMID:Ca2+ release from intracellular stores induced by afferent stimulation of CA3 pyramidal neurons in hippocampal slices. 883 43

Low Mg2+-induced epileptiform activity in the entorhinal cortex is characterized by an initial expression of seizure-like events followed by late recurrent discharges. Both these forms of activity as well as the transition between them were blocked by serotonin. In contrast, serotonin had little effect upon the epileptiform activity in areas CA3 and CA1 of the hippocampus. Both forms of epileptiform activity in the entorhinal cortex are sensitive to N-methyl-D-aspartate receptor antagonists and it is shown here that serotonin blocked both types of epileptiform activity through an effective concentration-dependent reduction of N-methyl-D-aspartate receptor-mediated excitatory postsynaptic potentials in deep layer entorhinal cortex cells. Serotonin also prolonged or even prevented the transition between the two types of epileptiform activity and we suggest that this may be through activation of the Na+/K+-ATPase. The resistance of epileptiform activity in CA1 and CA3 to serotonin was most likely related to the inability of serotonin to reduce Schaffer collateral-evoked excitatory postsynaptic potentials. Given the strong serotonergic inputs to both the hippocampus and entorhinal cortex, the differential sensitivity of the two regions to serotonin suggests functional differences. In addition since the late recurrent discharges in the entorhinal cortex are resistant to all clinically used anticonvulsants, serotonin may open new avenues for the development of novel anticonvulsant compounds.
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PMID:Serotonin blocks different patterns of low Mg2+-induced epileptiform activity in rat entorhinal cortex, but not hippocampus. 901 29

Previous results showed that Na+/K+-ATPase may have a functional relationship with the neurotransmitter serotonin which activates the glial sodium pump in the rat brain. Both the reaction rate (V) of Na+/K+-ATPase activity and [3H]ouabain binding were significantly increased in the presence of serotonin. It is not known, however, which alpha isoform is involved in the Na+/K+-ATPase response to serotonin and its regional distribution. Quantitative autoradiography of [3H]ouabain binding to rat brain slices was employed at different [3H]ouabain concentrations in order to gain information on both the distribution and the possible isoform involved. The results showed that 1500 nM [3H]ouabain binding was sensitive to serotonin 10(-3) M and significantly increased in the following brain regions: frontal cortex, areas CA1, CA2, and CA3 of the hippocampus, presubiculum, zona incerta, caudate putamen and the amygdaloid area, confirming and extending previous results. An effect of serotonin on brain but not kidney tissue at high, 1500 nM, and the lack of effect at low, 50 nM [3H]ouabain concentrations, strongly suggests the participation of the alpha2 isoform in the response of the pump to the neurotransmitter. Glial cells showed stimulation of ouabain binding by serotonin at ouabain concentrations above 350 nM. The present results open interesting questions related to the brain regions involved and the K+ handling by the glial alpha2 isoform of the pump.
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PMID:Serotonin modulation of low-affinity ouabain binding in rat brain determined by quantitative autoradiography. 969 Jul 35

Single-electrode voltage-clamp recordings were obtained from CA3 pyramidal cells in rat hippocampal organotypic slice cultures, and the slow Ca2+-dependent K+ current or afterhyperpolarization current (IAHP) was elicited with brief depolarizing voltage jumps. The slow IAHP was suppressed by the selective L-type Ca2+ channel antagonists isradipine (2 microM) or nifedipine (10 microM). In contrast, neither omega-conotoxin MVIIA (1 microM) nor omega-agatoxin IVA (200 nM), N-type and P/Q-type Ca2+ channel antagonists, respectively, attenuated this slow outward current. The slow IAHP was significantly reduced by thapsigargin (10 microM), a Ca2+ ATPase inhibitor that depletes intracellular Ca2+ stores, and by ryanodine (10-100 microM), which blocks Ca2+-induced Ca2+ release from intracellular compartments. At this concentration thapsigargin did not modify high-threshold Ca2+ current, which was, however, blocked by isradipine. Thus, in hippocampal CA3 pyramidal cells, Ca2+ influx through L-type Ca2+ channels is necessary to trigger the slow IAHP. Furthermore, intracellular Ca2+-activated Ca2+ stores represent a critical component in the transduction pathway leading to the generation of the slow IAHP.
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PMID:L-Type Ca2+ channels mediate the slow Ca2+-dependent afterhyperpolarization current in rat CA3 pyramidal cells in vitro. 981 42

A single cerebroventricular injection of ethacrynic acid (EA), a Cl(-)-ATPase inhibitor, induces generalized tonic-clonic convulsions in mice. To clarify whether such convulsive stimulus triggers a long-lasting rearrangement of the neural circuitry culminating in seizure susceptibility, we examined molecular, cellular and behavioral changes following the EA-induced seizure. The expression of immediate early gene c-fos mRNA as an index for cellular activation increased biphasically, with an early transient increase at 60 min and a late prolonged increase on the 10th to 14th day post-EA administration, most remarkably in the hippocampus and pyriform cortex. On the 14th day post-EA seizure, subconvulsive dose of kainic acid (5-17.5 mg/kg) caused severe (stage 5) seizure in 77% of the mice, with 70% mortality. In addition, the expression of nerve growth factor (NGF) also showed biphasic increases with close spatiotemporal correlation with c-fos expression. Moreover, the number of cell somata and the density of axon fibers of parvalbumin (PARV)-positive cells, a subpopulation of GABAergic interneurons, decreased in area dentata, CA1 and CA3 on the 7th and 14th day post-EA seizure. In area dentata and CA1, the density of glutamic acid decarboxylase (GAD)-positive cells also decreased on the 14th day. Thus, the transient EA-induced seizures appear to develop seizure susceptibility by causing damage of a subpopulation of inhibitory interneurons along with increases in the expression of c-fos and NGF in limbic structures.
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PMID:Long-lasting c-fos and NGF mRNA expressions and loss of perikaryal parvalbumin immunoreactivity in the development of epileptogenesis after ethacrynic acid-induced seizure. 1040 97

The oxidized purine nucleoside triphosphatase, hMTH1, has a critical role towards preventing errors caused by oxidized purine nucleoside triphosphates such as 8-oxo-dGTP and 2-hydroxy-dATP. We investigated the immunohistochemical expression of hMTH1 in human hippocampal postmortem tissues representing non-neurological disease and Alzheimer's disease (AD). In the non-neurological subjects the hMTH1 protein was enriched in the stratum lucidum at CA3 corresponding to mossy fiber synapses. In AD subjects, the synaptic immunoreactivities at CA3 were significantly decreased, whereas they tended to be increased at the entorhinal cortex. We suggest that the expression of hMTH1 indicates indirect evidence of oxidative stress and its regulation is regionally differentiated in AD.
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PMID:Expression of hMTH1 in the hippocampi of control and Alzheimer's disease. 1158 98


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