979 resultados para ATP-sensitive K( ) channel
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Plant cyanogenesis, the release of cyanide from endogenous cyanide-containing compounds, is an effective herbivore deterrent. This paper characterises cyanogenesis in the Australian tree Eucalyptus polyanthemos Schauer subsp. vestita L. Johnson and K. Hill for the first time. The cyanogenic glucoside prunasin ((R)-mandelonitrile beta-D-glucoside) was determined to be the only cyanogenic compound in E. polyanthemos foliage. Two natural populations of E. polyanthernos showed quantitative variation in foliar prumasin concentration, varying from zero (i.e. acyanogenic) to 2.07 mg CN g(-1) dry weight in one population and from 0.17 to 1.98 mg CN g(-1) dry weight in the other. No significant difference was detected between the populations with respect to the mean prunasin concentration or the degree of variation in foliar prunasin, despite significant differences in foliar nitrogen. Variation between individuals was also observed with respect to the capacity of foliage to catabolise prunasin to form cyanide. Moreover, variation in this capacity generally correlated with the amount of prunasin in the tissue, suggesting genetic linkage between prunasin and beta-glucosidase. (C) 2002 Elsevier Science Ltd. All rights reserved.
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Objective: To describe a new syndrome of X-linked myoclonic epilepsy with generalized spasticity and intellectual disability (XMESID) and identify the gene defect underlying this disorder. Methods: The authors studied a family in which six boys over two generations had intractable seizures using a validated seizure questionnaire, clinical examination, and EEG studies. Previous records and investigations were obtained. Information on seizure disorders was obtained on 271 members of the extended family. Molecular genetic analysis included linkage studies and mutational analysis using a positional candidate gene approach. Results: All six affected boys had myoclonic seizures and TCS; two had infantile spasms, but only one had hypsarrhythmia. EEG studies show diffuse background slowing with slow generalized spike wave activity. All affected boys had moderate to profound intellectual disability. Hyperreflexia was observed in obligate carrier women. A late-onset progressive spastic ataxia in the matriarch raises the possibility of late clinical manifestations in obligate carriers. The disorder was mapped to Xp11.2-22.2 with a maximum lod score of 1.8. As recently reported, a missense mutation (1058C>T/P353L) was identified within the homeodomain of the novel human Aristaless related homeobox gene (ARX). Conclusions: XMESID is a rare X-linked recessive myoclonic epilepsy with spasticity and intellectual disability in boys. Hyperreflexia is found in carrier women. XMESID is associated with a missense mutation in ARX. This disorder is allelic with X-linked infantile spasms (ISSX; MIM 308350) where polyalanine tract expansions are the commonly observed molecular defect. Mutations of ARX are associated with a wide range of phenotypes; functional studies in the future may lend insights to the neurobiology of myoclonic seizures and infantile spasms.
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We investigate the utility of nonclassical states of simple harmonic oscillators, particularly a superposition of coherent states, for sensitive force detection. We find that like squeezed states, a superposition of coherent states allows displacement measurements at the Heisenberg limit. Entangling many superpositions of coherent states offers a significant advantage over a single-mode superposition state with the same mean photon number.
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Calcium-activated potassium channels are a large family of potassium channels that are found throughout the central nervous system and in many other cell types. These channels are activated by rises in cytosolic calcium largely in response to calcium influx via voltage-gated calcium channels that open during action potentials. Activation of these potassium channels is involved in the control of a number of physiological processes from the firing properties of neurons to the control of transmitter release. These channels form the target for modulation for a range of neurotransmitters and have been implicated in the pathogenesis of neurological and psychiatric disorders. Here the authors summarize the varieties of calcium-activated potassium channels present in central neurons and their defining molecular and biophysical properties.
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Background: Mutations in SCN1A, the gene encoding the alpha1 subunit of the sodium channel, have been found in severe myoclonic epilepsy of infancy (SMEI) and generalized epilepsy with febrile seizures plus (GEFS(+)). Mutations in SMEI include missense, nonsense, and frameshift mutations more commonly arising de novo in affected patients. This finding is difficult to reconcile with the family history of GEFS(+) in a significant proportion of patients with SMEI Infantile spasms (IS), or West syndrome, is a severe epileptic encephalopathy that is usually symptomatic. In some cases, no etiology is found and there is a family history of epilepsy. Method: The authors screened SCN1A in 24 patients with SMEI and 23 with IS. Results: Mutations were found in 8 of 24 (33%) SMEI patients, a frequency much lower than initial reports from Europe and Japan. One mutation near the carboxy terminus was identified in an IS patient. A family history of seizures was found in 17 of 24 patients with SMEI. Conclusions: The rate of SCN1A mutations in this cohort of SMEI patients suggests that other factors may be important in SMEI. Less severe mutations associated with GEFS(+) could interact with other loci to cause SMEI in cases with a family history of GEFS(+). This study extends the phenotypic heterogeneity of mutations in SCN1A to include IS.
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Fifth-grade children were given a series of word reading tasks. First, two sets of 16 disyllabic words with medial VCV spellings, and with a long initial vowel were selected, varying in frequency but with similar word-initial segments. Nonwords were derived from these sets of words by exchanging initial onsets. Children read these nonwords in a first testing session. In a second test session, children were given the Woodcock Word Identification Test and the set of analogue words from which the nonwords were derived. Initial analyses examined only nonwords derived from words that were correctly read. Both sets of nonwords were more likely to be read with a long initial vowel than a short initial vowel, although this tendency was stronger in nonwords derived from high frequency words. Furthennore, Word Identification ability showed a strong relationship with the preference for long initial vowels in this type of disyllabic nonword, both for nonwords derived from known analogues and for nonwords derived from words that children could not read correctly. This preference was also correlated with the preference for context-sensitive grapheme-phoneme correspondences in the reading of ambiguous monosyllabic nonwords.These results have strong implications for current theories of word reading.
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Background There are few population-based data on long-term management of patients after coronary artery bypass graft (CABG), despite the high risk for future major vascular events among this group. We assessed the prevalence and correlates of pharmacotherapy for prevention of new cardiac events in a large population-based series. Methods A postal survey was conducted of 2500 randomly selected survivors from a state population of patients 6 to 20 years after first CABG. Results Response was 82% (n = 2061). Use of antiplatelet agents (80%) and statins (64%) declined as age increased. Other independent predictors of antiplatelet use included statin use (odds ratio [OR] 1.6, 95% CI 1.26-2.05) and recurrent angina (OR 1.6, CI 1.17-2.06). Current smokers were less likely to use aspirin (OR 0.59, CI 0.4-0.89). Statin use was associated with reported high cholesterol (OR 24.4, CI 8.4-32.4), management by a cardiologist (OR 2.3, CI 1.8-3.0), and the use of calcium channel-blockers. Patients reporting hypertension or heart failure, in addition to high cholesterol, were less likely to use statins. Angiotensin-converting enzyme inhibitors were the most commonly prescribed agents for management of hypertension (59%) and were more frequently used among patients with diabetes and those with symptoms of heart failure. Overall 42% of patients were on angiotensin-converting enzyme inhibitors and 36% on beta-blockers. Conclusions Gaps exist in the use of-recommended medications after CABG. Lower anti-platelet and statin use was associated with older age, freedom from angina, comorbid heart failure or hypertension, and not regularly visiting a cardiologist. Patients who continue to smoke might be less likely to adhere to prescribed medications.
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To better understand the biochemical mechanisms underlying anisosmotic extracellular regulation in the freshwater Brachyura, we kinetically characterized the V-ATPase from the posterior gills of Dilocarcinus pagei, acclimated for 10 days to salinities up to 21%.. Specific activity was highest in fresh water (26.5 +/- 2.1 U mg(-1)), decreasing in 5 parts per thousand to 21 parts per thousand, attaining 3-fold less at 15 parts per thousand. Apparent affinities for ATP and Mg(2+) respectively increased 3.2- and 2-fold at 10 parts per thousand, suggesting expression of different isoenzymes. In a 240-h time-course study of exposure to 21%., maximum specific activity decreased 2.5- to 4-fold within 1 to 24 h while apparent affinities for ATP and Mg(2+) respectively increased by 12-fold within 24 h and 2.4-fold after 1 h, unchanged thereafter. K(I) for bafilomycin A(1) decreased 150-fold after 1 h, remaining constant up to 120 h. This is the first kinetic analysis of V-ATPase specific activity in crustacean gills during salinity acclimation. Our findings indicate active gill Cl(-) uptake by D. pagei in fresh water, and short- and long-term down-regulation of V-ATPase-driven ion uptake processes during salinity exposure, aiding in comprehension of the biochemical adaptations underpinning the establishment of the Brachyura in fresh water. (C) 2011 Elsevier Inc. All rights reserved.
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Using whole cell recordings from acute slices of the rat amygdala, we have examined the physiological properties of and synaptic connectivity to neurons in the lateral sector of the central amygdala (CeA). Based on their response to depolarizing current injections, CeA neurons could be divided into three types. Adapting neurons fired action potentials at the start of the current injections at high frequency and then showed complete spike-frequency adaptation with only six to seven action potentials evoked with suprathreshold current injections. Late-firing neurons fired action potentials with a prolonged delay at threshold but then discharged continuously with larger current injections. Repetitive firers discharged at the start of the current injection at threshold and then discharged continuously with larger current injections. All three cells showed prolonged afterhyperpolarizations (AHPs) that followed trains of action potentials. The AHP was longer lasting with a larger slow component in adapting neurons. The AHP in all cell types contained a fast component that was inhibited by the SK channel blocker UCL1848. The slow component, not blocked by UCL1848, was blocked by isoprenaline and was significantly larger in adapting neurons. Blockade of SK channels increased the discharge frequency in late firers and regular-spiking neurons but had no effect on adapting neurons. Blockade of the slow AHP with isoprenaline had no effect on any cell type. All cells received a mixed glutamatergic and GABAergic input from a medial pathway. Electrical stimulation of the lateral (LA) and basolateral (BLA)nuclei evoked a large monosynaptic glutamatergic response followed by a disynaptic inhibitory postsynaptic potential. Activation of neurons in the LA and BLA by puffer application of glutamate evoked a small monosynaptic response in 13 of 55 CeA neurons. Local application of glutamate to the CeL evoked a GABAergic response in all cells. These results show that at least three types of neurons are present in the CeA that can be distinguished on their firing properties. The firing frequency of two of these cell types is determined by activation of SK channels. Cells receive a small input from the LA and BLA but may receive inputs that course through these nuclei en route to the CeA.
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Diadromous freshwater shrimps are exposed to brackish water both as an obligatory part of their larval life cycle and during adult reproductive migration; their well-developed osmoregulatory ability is crucial to survival in such habitats. This study examines gill microsomal Na,K-ATPase (K-phosphatase activity) kinetics and protein profiles in the freshwater shrimp Macrobrachium amazonicum when in fresh water and after 10-days of acclimation to brackish water (21 parts per thousand salinity), as well as potential routes of Na(+) uptake across the gill epithelium in fresh water. On acclimation, K-phosphatase activity decreases 2.5-fold, Na,K-ATPase alpha-subunit expression declines, total protein expression pattern is markedly altered, and enzyme activity becomes redistributed into different density membrane fractions, possibly reflecting altered vesicle trafficking between the plasma membrane and intracellular compartments. Ultrastructural analysis reveals an intimately coupled pillar cell-septal cell architecture and shows that the cell membrane interfaces between the external medium and the hemolymph are greatly augmented by apical pillar cell evaginations and septal cell inviginations, respectively. These findings ire discussed regarding the putative movement of Na(+) across the pillar cell interfaces and into the hemolymph via the septal cells, powered by the Na,K-ATPase located in their invaginations. (C) 2008 Elsevier Inc. All rights reserved.
Resumo:
Different stoichiometries are observed between alpha and beta subunits of Na,K-ATPase that depend on the method employed to solubilize and purify the enzyme. It is not known whether this variability is due to loss of protein-protein association, or is a result of the replacement of essential phospholipids by detergent molecules. With the aim of understanding the effect of enzyme/surfactant ratio on both the catalytic activity and the enzyme structure, we have investigated the bulk and surface properties of the enzyme. The circular dichroism (CD) spectra, surface tension and dilatational surface elasticity results were compared with the residual ATPase activity of the Na,K-ATPase in different surfactant and protein concentrations. Na,K-ATPase in the (alpha beta)(2) form dissociated to the alpha beta form on dilution, and associated to the (alpha beta)(4) form when concentrated. These different stoichiometries have similar ATPase activities and are in equilibrium at C(12)E(8) concentrations below the CIVIC (0.053 mg mL(-1)). At detergent concentrations above the CIVIC the ATPase activity of all forms was abolished, which is concomitant with the dissociation of the a and subunits. (C) 2008 Elsevier Inc. All rights reserved.