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Na+ Influx (na+ + influx)
Selected AbstractsThe effect of food rations on tissue-specific copper accumulation patterns of sublethal waterborne exposure in Cyprinus carpioENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 7 2007Shodja Hashemi Abstract Common carp (Cyprinus carpio) were fed to two different food rations, 0.5% body weight (low ration [LR]) and 5% body weight (high ration [HR]), and were exposed to sublethal (1 ,M) copper levels for 28 d in softened Antwerp (Belgium) city tap water (Ca2+, 79.3 mg/L; Mg2+, 7.4 mg/L; Na+, 27.8 mg/L; pH 7.5,8.0). Copper accumulations in the liver, gills, kidney, anterior intestine, posterior intestine, and muscle were determined. Copper accumulation in the gills, liver, and kidney of LR fish was significantly higher than in HR fish. The only time copper uptake in HR fish was significantly higher than in LR fish was in the posterior intestine after two weeks of exposure. No difference was found between the two rations in the anterior intestine. Copper accumulation in the liver of both feeding treatments occurred in a time-dependent manner and did not reach steady state in any treatment. On the contrary, copper concentration in the gills reached a steady state for both HR and LR fish within the first week of exposure. No copper accumulation was found in muscle tissues of either treatment. Copper concentration dropped to control levels in all tissues, except liver tissue, two weeks after the exposure ended. Our studies indicated that copper uptake was influenced by the food ration in carp. The difference in copper accumulation probably is related to the amount of dietary NaCl and different rates of metallothionein synthesis. Low food availability provides less Na+ influx and leads to increased brachial uptake of Na+ and copper. In addition, it has been shown that starved animals show increased levels of metallothionein, possibly causing higher copper accumulation. [source] Mechanistic hypotheses for nonsynaptic epileptiform activity induction and its transition from the interictal to ictal state,Computational simulationEPILEPSIA, Issue 11 2008Antônio-Carlos G. De Almeida Summary Purpose:, The aim of this work is to study, by means of computational simulations, the induction and sustaining of nonsynaptic epileptiform activity. Methods:, The computational model consists of a network of cellular bodies of neurons and glial cells connected to a three-dimensional (3D) network of juxtaposed extracellular compartments. The extracellular electrodiffusion calculation was used to simulate the extracellular potential. Each cellular body was represented in terms of the transmembrane ionic transports (Na+/K+ pumps, ionic channels, and cotransport mechanisms), the intercellular electrodiffusion through gap-junctions, and the neuronal interaction by electric field and the variation of cellular volume. Results:, The computational model allows simulating the nonsynaptic epileptiform activity and the extracellular potential captured the main feature of the experimental measurements. The simulations of the concomitant ionic fluxes and concentrations can be used to propose the basic mechanisms involved in the induction and sustaining of the activities. Discussion:, The simulations suggest: The bursting induction is mediated by the Cl, Nernst potential overcoming the transmembrane potential in response to the extracellular [K+] increase. The burst onset is characterized by a critical point defined by the instant when the Na+ influx through its permeable ionic channels overcomes the Na+/K+ pump electrogenic current. The burst finalization is defined by another critical point, when the electrogenic current of the Na+/K+ pump overcomes its influx through the channels. [source] Mechanisms of substrate transport-induced clustering of a glial glutamate transporter GLT-1 in astroglial,neuronal culturesEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 9 2008Takayuki Nakagawa Abstract Glutamate uptake by the Na+ -dependent glutamate transporter GLT-1, which is predominantly expressed in astrocytes, is crucial for regulating glutamate concentration at the synaptic cleft and achieving proper excitatory neurotransmission. A body of evidence suggests that GLT-1 constitutively traffics between the plasma membrane and endosomes via an endocytosis/recycling pathway, and forms a cluster. Here, we report substrate transport via GLT-1-induced formation of GLT-1 cluster accompanied by intracellular trafficking in rat astroglial,neuronal cultures. We constructed a recombinant adenovirus expressing enhanced green fluorescence protein (EGFP)-tagged GLT-1. Adenoviral infection resulted in the expression of functional GLT-1,EGFP preferentially in astrocytes, partly as clusters. Treatment with glutamate, but not N -methyl-D-aspartate, dramatically increased the number of GLT-1 clusters within 1 h. The estimated EC50 value of glutamate was 240 ,m. In addition, glutamate decreased the cell surface expression and increased the intracellular expression of GLT-1. The GLT-1 clusters were found in early and recycling endosomes and partly in lysosomes, and were inhibited by blockade of endocytotic pathways. Ionotropic and metabotropic glutamate receptor antagonists had no effect on glutamate-induced GLT-1 clustering. The non-transportable glutamate uptake inhibitors (2S,3S)-3-[3-[4-(trifluoromethyl)benzoylamino]benzyloxy]aspartate and dihydrokainate, as well as Na+ -free conditions, prevented the glutamate-induced GLT-1 clustering, whereas the competitive substrates, aspartate and L- trans -pyrrolidine-2,4-dicarboxylate, induced GLT-1 clustering. Furthermore, the Na+/K+ -ATPase inhibitor, ouabain, and the Na+ ionophores, gramicidin and monensin, produced GLT-1 clustering. Modulators of intracellular Ca2+signaling or membrane depolarization had no effect on GLT-1 clustering. Taken together, these results suggest that Na+ influx associated with GLT-1 substrate transport triggers the formation of GLT-1 clusters accompanied by intracellular trafficking via endocytotic pathways in astrocytes. [source] Dynamics of Ca2+ and Na+ in the dendrites of mouse cerebellar Purkinje cells evoked by parallel fibre stimulationEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 10 2003Akinori Kuruma Abstract Ca2+ and Na+ play important roles in neurons, such as in synaptic plasticity. Their concentrations in neurons change dynamically in response to synaptic inputs, but their kinetics have not been compared directly. Here, we show the mechanisms and dynamics of Ca2+ and Na+ transients by simultaneous monitoring in Purkinje cell dendrites in mouse cerebellar slices. High frequency parallel fibre stimulation (50 Hz, 3,50-times) depolarized Purkinje cells, and Ca2+ transients were observed at the anatomically expected sites. The magnitude of the Ca2+ transients increased linearly with increasing numbers of parallel fibre inputs. With 50 stimuli, Ca2+ transients lasted for seconds, and the peak [Ca2+] reached ,100 µm, which was much higher than that reported previously, although it was still confined to a part of the dendrite. In contrast, Na+ transients were sustained for tens of seconds and diffused away from the stimulated site. Pharmacological interventions revealed that Na+ influx through ,-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors and Ca2+ influx through P-type Ca channels were essential players, that AMPA receptors did not operate as a Ca2+ influx pathway and that Ca2+ release from intracellular stores through inositol trisphosphate receptors or ryanodine receptors did not contribute greatly to the large Ca2+ transients. [source] In depolarized and glucose-deprived neurons, Na+ influx reverses plasmalemmal K+ -dependent and K+ -independent Na+/Ca2+ exchangers and contributes to NMDA excitotoxicityJOURNAL OF NEUROCHEMISTRY, Issue 6 2002Aneta Czy Abstract Cerebellar granule cells (CGCs) express K+ -dependent (NCKX) and K+ -independent (NCX) plasmalemmal Na+/Ca2+ exchangers which, under plasma membrane-depolarizing conditions and high cytosolic [Na+], may reverse and mediate potentially toxic Ca2+ influx. To examine this possibility, we inhibited NCX or NCKX with KB-R7943 or K+ -free medium, respectively, and studied how gramicidin affects cytosolic [Ca2+] and 45Ca2+ accumulation. Gramicidin forms pores permeable to alkali cations but not Ca2+. Therefore, gramicidin-induced Ca2+ influx is indirect; it results from fluxes of monovalent cations. In the presence of Na+, but not Li+ or Cs+, gramicidin induced Ca2+ influx that was inhibited by simultaneous application of KB-R7943 and K+ -free medium. The data indicate that gramicidin-induced Na+ influx reverses NCX and NCKX. To test the role of NCX and/or NCKX in excitotoxicity, we studied how NMDA affects the viability of glucose-deprived and depolarized CGCs. To assure depolarization of the plasma membrane, we inhibited Na+,K+ -ATPase with ouabain. Although inhibition of NCX or NCKX reversal failed to significantly limit 45Ca2+ accumulation and excitotoxicity, simultaneously inhibiting NCX and NCKX reversal was neuroprotective and significantly decreased NMDA-induced 45Ca2+ accumulation. Our data suggest that NMDA-induced Na+ influx reverses NCX and NCKX and leads to the death of depolarized and glucose-deprived neurons. [source] The cyclic nucleotide-gated channel, AtCNGC10, influences salt tolerance in ArabidopsisPHYSIOLOGIA PLANTARUM, Issue 3 2008Kun-Mei Guo Cyclic nucleotide-gated channels (CNGCs) in the plasma membrane transport K+ and other cations; however, their roles in the response and adaptation of plants to environmental salinity are unclear. Growth, cation contents, salt tolerance and K+ fluxes were assessed in wild-type and two AtCNGC10 antisense lines (A2 and A3) of Arabidopsis thaliana (L.) Heynh. Compared with the wild-type, mature plants of both antisense lines had altered K+ and Na+ concentrations in shoots and were more sensitive to salt stress, as assessed by biomass and Chl fluorescence. The shoots of A2 and A3 plants contained higher Na+ concentrations and significantly higher Na+/K+ ratios compared with wild-type, whereas roots contained higher K+ concentrations and lower Na+/K+ ratios. Four-day-old seedlings of both antisense lines exposed to salt stress had smaller Na+/K+ ratios and longer roots than the wild-type. Under sudden salt treatment, the Na+ efflux was higher and the K+ efflux was smaller in the antisense lines, indicating that AtCNGC10 might function as a channel providing Na+ influx and K+ efflux at the root/soil interface. We conclude that the AtCNGC10 channel is involved in Na+ and K+ transport during cation uptake in roots and in long-distance transport, such as phloem loading and/or xylem retrieval. Mature A2 and A3 plants became more salt sensitive than wild-type plants because of impaired photosynthesis induced by a higher Na+ concentration in the leaves. [source] The gene sll0273 of the cyanobacterium Synechocystis sp. strain PCC6803 encodes a protein essential for growth at low Na+/K+ ratiosPLANT CELL & ENVIRONMENT, Issue 6 2000S. Mikkat ABSTRACT A mutant of Synechocystis sp. strain PCC6803 was obtained by random cartridge mutagenesis, which could not grow at low sodium concentrations. Genetic analyses revealed that partial deletion of the sll0273 gene, encoding a putative Na+/H+ exchanger, was responsible for this defect. Physiological characterization indicated that the sll0273 mutant exhibited an increased sensitivity towards K+, even at low concentrations, which was compensated for by enhanced concentrations of Na+. This enhanced Na+ demand could also be met by Li+. Furthermore, addition of monensin, an ionophore mediating electroneutral Na+/H+ exchange, supported growth of the mutant at unfavourable Na+/K+ ratios. Measurement of internal Na+ and K+ contents of wild-type and mutant cells revealed a decreased Na+/K+ ratio in mutant cells pre-incubated at a low external Na+/K+ ratio, while it remained at the level of the wild type after pre-incubation at a high external Na+/K+ ratio. We conclude that the Sll0273 protein is required for Na+ influx, especially at low external Na+ concentrations or low Na+/K+ ratios. This system may be part of a sodium cycle and may permit re-entry of Na+ into the cells, if nutrient/Na+ symporters are not functional or operating. [source] Activity-dependent regulation of voltage-gated Na+ channel expression in Mat-LyLu rat prostate cancer cell lineTHE JOURNAL OF PHYSIOLOGY, Issue 2 2006William J. Brackenbury We have shown previously that voltage-gated Na+ channels (VGSCs) are up-regulated in human metastatic disease (prostate, breast and small-cell lung cancers), and that VGSC activity potentiates metastatic cell behaviours. However, the mechanism(s) regulating functional VGSC expression in cancer cells remains unknown. We investigated the possibility of activity-dependent (auto)regulation of VGSC functional expression in the strongly metastatic Mat-LyLu model of rat prostate cancer. Pretreatment with tetrodotoxin (TTX) for 24,72 h subsequently suppressed peak VGSC current density without affecting voltage dependence. The hypothesis was tested that the VGSC auto-regulation occurred via VGSC-mediated Na+ influx and subsequent activation of protein kinase A (PKA). Indeed, TTX pretreatment reduced the level of phosphorylated PKA, and the PKA inhibitor KT5720 decreased, whilst the adenylate cyclase activator forskolin and the Na+ ionophore monensin both increased the peak VGSC current density. TTX reduced the mRNA level of Nav1.7, predominant in these cells, and VGSC protein expression at the plasma membrane, although the total VGSC protein level remained unchanged. TTX pretreatment eliminated the VGSC-dependent component of the cells' migration in Transwell assays. We concluded that the VGSC activity in Mat-LyLu rat prostate cancer cells was up-regulated in steady-state via a positive feedback mechanism involving PKA, and this enhanced the cells' migratory potential. [source] Persistent (current) in the face of adversity , A new class of cardiac anti-ischaemic compounds on the horizon?BRITISH JOURNAL OF PHARMACOLOGY, Issue 2 2009David A Saint Although a persistent component of the sodium current (INaP) was described in cardiac tissue about three decades ago, its physiological role and potential as a therapeutic target was not immediately apparent. Subsequent demonstrations that INaP is enhanced by hypoxia and ischaemia, and that Na+ influx via INaP may contribute to cellular damage, diastolic dysfunction and arrhythmias during ischaemia and reperfusion, raised interest in INaP as a target for anti-ischaemic drugs. Several agents have now been developed to clinical stages, which have INaP block as either their main action, or as a useful co-effect. In this issue of the British Journal of Pharmacology, Vacher et al. report the anti-ischaemic actions of F15845, which appears to exhibit the most selective block of INaP yet described. Its efficacy in animal models of angina raises the prospect of new, specific, INaP blockers that may represent a largely unexploited opportunity for a new class of anti-ischaemic compounds. [source] ROLE OF EXTRACELLULAR Na+, Ca2+ -ACTIVATED Cl - CHANNELS AND BK CHANNELS IN THE CONTRACTION OF Ca2+ STORE-DEPLETED TRACHEAL SMOOTH MUSCLECLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 7 2009Catalina Romero-Méndez SUMMARY 1In the present study, we investigated the series of events involved in the contraction of tracheal smooth muscle induced by the re-addition of Ca2+ in an in vitro experimental model in which Ca2+ stores had been depleted and their refilling had been blocked by thapsigargin. 2Mean (±SEM) contraction was diminished by: (i) inhibitors of store-operated calcium channels (SOCC), namely 100 µmol/L SKF-96365 and 100 µmol/L 1-(2-trifluoromethylphenyl) imidazole (to 66.3 ± 4.4 and 41.3 ± 5.2% of control, respectively); (ii) inhibitors of voltage-gated Ca2+ channels CaV1.2 channels, namely 1 µmol/L nifedipine and 10 µmol/L verapamil (to 86.2 ± 3.4 and 76.9 ± 5.9% of control, respectively); and (iii) 20 µmol/L niflumic acid, a non-selective inhibitor of Ca2+ -dependent Cl, channels (to 41.1 ± 9.8% of control). In contrast, contraction was increased 2.3-fold by 100 nmol/L iberiotoxin, a blocker of the large-conductance Ca2+ -activated K+ (BK) channels. 3Furthermore, contraction was significantly inhibited when Na+ in the bathing solution was replaced by N -methyl,d -glucamine (NMDG+) to 39.9 ± 7.2% of control, but not when it was replaced by Li+ (114.5 ± 24.4% of control). In addition, when Na+ had been replaced by NMDG+, contractions were further inhibited by both nifedipine and niflumic acid (to 3.0 ± 1.8 and 24.4 ± 8.1% of control, respectively). Nifedipine also reduced contractions when Na+ had been replaced by Li+ (to 10.7 ± 3.4% to control), the niflumic acid had no effect (116.0 ± 4.5% of control). 4In conclusion, the data of the present study demonstrate the roles of SOCC, BK channels and CaV1.2 channels in the contractions induced by the re-addition of Ca2+ to the solution bathing guinea-pig tracheal rings under conditions of Ca2+ -depleted sacroplasmic reticulum and inhibition of sarcoplasmic/endoplasmic reticulum calcium ATPase. The contractions were highly dependent on extracellular Na+, suggesting a role for SOCC in mediating the Na+ influx. [source] | |||||||||||||||||||||||||