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PubMedDate not supplied

[Effect of glucocorticoids on electrolyte excretion after expansion of the extracellular space].

The influence of glucocorticosteroids (cortisone, hydrocortisone, prednisone, dexamethasone, and triamcinolone) on the volumetric natriuresis was studied in experiments on rats. Natriuresis proved to increase considerably after the widening of the extracellular space, and exceeded sodium excretion in control animals after a similar increase of the fluid volume in control animals. Intensification of the natriuretic response to the increase of the extracellular fluid volume against the background of glucocorticoids apparently occurred as a result of production or activation under the influence of these hormone of the natriuretic factor.

Animals↗

PubMed1995

Metabolism of [3-3H]oleanolic acid in the isolated Calendula officinalis leaf cells and transport of the synthesized glycosides to the cell wall and the extracellular space.

It has been shown for the first time that [3-3H]oleanolic acid glycosides formed in the cytosol of C. officinalis leaf cells are transported to the extracellular space in the form of pentaglucoside VI (44%), whereas glucuronides derived from [3-3H]oleanolic acid 3-O-monoglucuronide (29%) as well as a part of glucosides (24%) were transported into the cell walls.

Biological Transport↗

PubMed1985

Changes in sodium activity during light stimulation in photoreceptors, glia and extracellular space in drone retina.

Ion-selective micro-electrodes were used to measure Na+ activity, aNa, in the two types of cell, photoreceptors and glial cells, and in the extracellular space, in superfused slices of the retina of the honey-bee drone, Apis mellifera male. Movements of Na+ were induced by light stimulation, or by increasing [K+] in the superfusate. In the dark, aNa in the photoreceptors was 10 mM (S.E. of the mean = 1 mM); in the glial cells it was higher: 37 +/- 2 mM. We estimate that in this preparation about 2/3 of the free Na+ in the tissue is in the glial cells. Stimulation with a train of light flashes, 1 s-1 for 90 s caused aNa in the photoreceptors to increase by 16 +/- 2 mM. K+ activity, aK, decreased by 21 +/- 3 mM. During the standard train of light flashes, aNa in glial cells decreased by only 1.5 +/- 0.3 mM, much less than the increase in aK (7 +/- 2 mM). One possible interpretation of this result is that most of the increase in aK is due to K+ uptake by a mechanism other than Na+-K+ exchange. In extracellular fluid, stimulation caused aNa to fall to a relatively steady value in about 10 s. Unlike aK, there was no tendency for aNa to return to the base line during the remainder of the 90 s stimulation. The fall in aNa was 14 +/- 1 mM: a greater fall is prevented by extracellular electric currents and a decrease in extracellular volume. When [K+] in the superfusate was increased from 7.5 to 18 mM, aNa decreased in the glial cells but not in the photoreceptors. In this tissue, stimulation causes changes in aNa in the neurones that might be large enough to modify the biochemistry of the cells. But in the glia, the fractional changes are small.

Action Potentials↗

PubMed1977

Paracellular permeability of extracellular space markers across rat jejunum in vitro. Indication of a transepithelial fluid circuit.

1. The characteristics of [51Cr]EDTA, [3H]methoxyinulin ([3H]MI), [14C]polyethylene glycol-4000 ([14C]PEG), and [3H]mannitol as markers of the extracellular space (e.c.s.) of isolated mucosa from the rat small intestine have been examined. 2. Unidirectional transmural fluxes across the rat jejunum of [3H]MI, [14C]PEG and [3H]mannitol have been measured in the absence of glucose or in the presence of 28 mM glucose. 3. Assuming that [14C]PEG does not enter the cells, [51Cr]EDTA and [3H]mannitol seem to have access to approximately 50 and 90% of the intracellular water respectively. 4. The commercially availabel [3H]MI had access to a space which exceeded th [14C]PEG space by 10%. Upon purification by gel filtration the high molecular weight fraction of the [3H]MI provided estimates of the e.c.s. identical with the estimates obtained with [14C]PEG. 5. For all the markers used the e.c.s. estimates remained constant between the 40th and 80th min of incubation. 6. In the absence of glucose the transepithelial net fluxes of each of the different markers were zero. In the presence of 28 mM glucose the serosato-mucosa fluxes of all markers were dramatically increased. The ratio between the serosa-to-mucosa and the mucosa-to-serosa fluxes increased in the order [3H]mannitol greater than [3H]MI greater than [14C]PEG. 7. The effect of glucose on the flux ratio of the marker substances suggests that glucose-induced net water transport to the serosa side of the gut wall represents the difference between a transcellular net water transport to the serosal side and a significant paracellular net water transport through the lateral intercellular spaces to the mucosal solution.

Animals↗

PubMed1979

Extracellular space and diffusion barriers in muscle fibres from Megabalanus psittacus (Darwin).

1. Muscle fibres from Megabalanus psittacus (Darwin) were used to measure the exchange of Na+ and Ca2+ between intracellular and extracellular compartments. 2. The size of the extracellular space was evaluated directly from electron micrographs at 6.1 +/- 0.5% (percentage of the fibre volume). The more conventional estimates using Na+ and 134Cs+ as space markers gave higher values, namely, 8.9 +/- 0.7 and 9.5 +/- 1.5%. 3. An average value of 9.2% was used to correct the total Na+ and K+ in the muscle fibres and to estimate the intracellular concentrations of Na+ and K+ as 39 +/- 4 and 202 +/- 11 mM respectively. 4. Na+ (and similar Ca2+) washout curves could be described using a three compartments diffusion model. The data analysed in terms of this model enabled us to estimate membrane permeabilities as PNa+ = 2.7 x 10(-7) and PCa2+ = 2.7 x 10(-7) cm/sec.

Animals↗

PubMed1993

Glucose-induced water movement from the intracellular to the extracellular space and its influence on calculations of glucose metabolism.

The osmotic effect of intravenous glucose was investigated in eight healthy volunteers. Increases in plasma glucose can induce water movement from the intracellular to the extracellular space. Serum choline esterase was used as an endogenous marker of serum dilution. Intravenous tests with 5, 15, 30 and 35 g of glucose showed that the water shift was proportional to the amount infused. The respective dilutions of choline esterase were 1.3 +/- 0.7%, 3.3 +/- 0.9%, 6.3 +/- 0.8% and 7.8 +/- 0.5%. The effect on extracellular water was maintained when plasma glucose remained elevated (inhibition of insulin secretion with a somatostatin analogue). In comparison to glucose, infusion of 10 g of a mixture of amino acids produced a less pronounced effect than expected. The acute water shift after intravenous glucose dilutes serum components including glucose (8% of total extracellular glucose at 35 g). This can be misinterpreted as glucose clearance when calculating metabolic rates. For estimated amounts a proportional correction should be made (3.5% per 5 mmol l-1 increase). A measured plasma glucose of 22.2 mmol l-1 should be corrected to 24.8 mmol l-1, while a plasma glucose value of 5.0 mmol l-1 needs no correction.

Blood Glucose↗

PubMed2003

Measurement of the extracellular space in brain tumors using 76Br-bromide and PET.

UNLABELLED: Brain edema significantly contributes to the clinical course of human brain tumor patients. There is evidence that an enlargement of the extracellular space (ECS) is involved in the development of brain edema. Although T2-weighted magnetic resonance (T2-MR) images represent brain edema by its increased water content, they do not differentiate ECS enlargement from increased intracellular water content. METHODS: On the basis of the known distribution of bromide in the ECS, we used (76)Br-bromide and PET to measure the regional ECS in 9 brain tumor patients. Transport rate constants and the distribution volume (DV) of (76)Br-bromide in normal brain and tumor were derived from dynamic PET scans and the measured (76)Br-bromide concentration in arterial plasma. We evaluated different models regarding their reliability in estimating the ECS. RESULTS: Assuming that the DV of (76)Br-bromide represents the ECS, robust estimates were possible for all investigated regions. In normal brain, ECS was within a narrow range-for example, occipital lobe, 19.9% +/- 3.1%-and was lower in 2 dexamethasone-treated patients compared with untreated patients. In 7 of 9 tumors, increased ECS ranged between 43.8% and 61.1%. ECS increases were confined to the tumor mass and did not extend into peritumoral edematous brain. Two patients with large hyperintense lesions according to T2-MR images showed normal ECS values within the lesion. CONCLUSION: (76)Br-Bromide PET allows a quantitative measurement of the ECS in brain edema and in normal brain. The discrepancies between lesions shown by T2-MRI and regional ECS enlargement as measured with PET challenge the concept of tumor-induced brain edema.

Adult↗

PubMed1978

Changes in the potassium ion concentration in the extracellular space of rat cerebral cortex during the arousal reaction.

The integrative activity of K+ ions in the CNS was studied in urethane-anaesthetized rats. Changes in the potassium ion concentration in the extracellular space ([K+]e) of the cerebral cortex were studied by means of ion-selective K+ microelectrodes introduced into the brain with an implanted micro-drive allowing measurement in the immobilized animal. EEG desynchronizations evoked by various arousal stimuli or of spontaneous origin were accompanied by a small, but definitely measurable and reliably reproducible [K+]e increment. In arousal reactions evoked by nociceptive stimuli and ammonia fumes, [K+]e rose from a resting value of 3 mM by a mean 0.31 +/- 0.04 mM and 0.61 +/- 0.15 mM respectively. The mean duration of the increase was 37 and 305 sec and the mean duration of corresponding EEG desynchronization 47 and 48 sec; the amplitude of the [K+]e change lagged 15 and 39 sec behind maximum EEG desynchronization. Periodic spontaneous desynchronizations lasting 123 sec, which were evidently associated with the sleep cycle and were accompanied by a [K+]e increment of 0.4 +/- 0.04 mM, occurred in two rats. Repeated nociceptive stimuli led to the elaboration of a conditioned arousal reaction manifested in a [K+]e increment prior to their application. [K+]e changes in arousal reactions were found to be a more sensitive index of the general activity of the neuronal population than DC potential changes.

Animals↗

PubMed1991

Extracellular space volume changes in the rat spinal cord produced by nerve stimulation and peripheral injury.

Double-barrelled potassium and tetramethylammonium-sensitive microelectrodes were used in diffusion studies with tetramethylammonium ions, which remain essentially extracellular during the measurements. Activity-related changes in the extracellular space (ECS) volume fraction (alpha), ECS tortuosity (lambda) and the dynamics of the ECS volume changes were examined in the spinal dorsal horns of rats. The alpha and lambda in L4 and L5 segments of unstimulated rats were alpha = 0.24 +/- 0.01 (i.e. ECS occupied 24 +/- 1% of the total spinal cord volume) and lambda = 1.54 +/- 0.04 (mean +/- S.D. of mean, n = 21). The values were not significantly different throughout the dorsal horn. Repetitive electrical stimulation of peripheral nerves at 3-100 Hz increased extracellular potassium concentration [( K+]e) and ECS volume in Rexed laminae III-V by 15.8 +/- 2.7% (n = 5). After the end of stimulation, when the [K+]e decreased below the original baseline (K+ undershoot), the ECS volume decreased by 20-45%. The magnitude and duration of ECS volume decrease were positively related to the stimulation frequency and duration. The ECS volume decrease was maximal at 2-10 min after the stimulation had been discontinued, and it returned to the prestimulation values in 15-40 min. The ECS volume decreased by 20-50% after injury of the ipsilateral hind paw evoked either by subcutaneous injection of turpentine (n = 5), or by thermal injury (n = 6). The maximal changes were found in Rexed laminae III-V, 5-10 min after injection of turpentine and 10-25 min after thermal injury, and persisted for more than 120 min and 30 min, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1984

Changes in extracellular space in optic nerves of regenerative and nonregenerative animals after hypertonic fixation: implications for axon regeneration.

The optic nerves of some regenerative and nonregenerative animals were compared using electron microscopy, after hypertonic perfusion. Optic axons and glial cell processes separated more readily in regenerative animals, creating large extracellular spaces. In mammals, cell processes remained in close proximity. These findings may indicate lesser adhesion between cell processes in optic nerves of regenerative animals, a characteristic that could allow "potential" space for axon regrowth after nerve injury.

Animals↗

PubMed1990

Atherosclerosis and molecular pathology: mechanisms of cholesteryl ester accumulation in foam cells and extracellular space of atherosclerotic lesions.

This article reviews aspects of the molecular pathology of cholesteryl ester accumulation in atherosclerotic lesions. 1. Transcytosis of lipoproteins through cultured endothelial monolayer. 2. Transformation to foam cell from macrophage. 3. Cholesteryl ester deposition in the extracellular space of atherosclerotic lesions. We also discuss the development and use of novel monoclonal antibodies recognizing atherosclerotic lesions and peroxidized lipoproteins prepared from atherosclerotic lesions.

Animals↗

PubMedDate not supplied

Determination of the extracellular space with nonradioactive Co3+EDTA and simultaneous estimation of Na, K, Ca, and Mg contents in isolated guinea-pig heart preparations by atomic absorption spectrometry.

A nonradioactive assay for the estimation of the size of the extracellular space (ECS) was developed utilizing Co3+EDTA as ECS marker. Co was measured by atomic absorption spectrophotometry. In a Langendorff preparation the compound was pharmacologically inert at a concentration of 3 X 10(-5) mol/l. The size of the ECS was independent of the ECS marker concentration indicating the lack of tissue adsorption. The filling of the ECS is almost completed after 3 min of perfusion. An insignificant slope of the late phase of the uptake curves in guinea-pig Langendorff heart preparations and isolated atria indicated no or very slow uptake into deep compartments. A sufficiently good estimate of the size of the ECS can be found after 15 min of equilibration. Simultaneous measurements of the size of the ECS and of ions (Na, K, Ca, Mg) can be performed within the same sample. Calculations of cellular Na, K, Mg, and Ca concentrations are in reasonable agreement with literature data.

Animals↗

PubMed1983

Potassium measurements in the extracellular spaces of normal and failing cat myocardium.

After periods of quiescence, papillary muscles and trabeculae from normal and hypertrophied-failing cat hearts were subjected to ionic stress induced by stimulation (drive) at different frequencies. Patterns of change in extracellular potassium concentration were measured using ion-selective microelectrodes and were shown to be significantly different in certain key parameters. In both types of tissue, extracellular potassium activity initially increased from the level in the bathing medium, reached a peak, and then returned toward the original levels. However, the time for this to occur was significantly longer in the hypertrophied-failing muscles than in the normal controls. Also, after more than 5 min of drive, the potassium activity in the extracellular spaces was significantly higher in the hypertrophied-failing tissue than in the normal tissue. The results of these experiments indicate that there may be quantitative differences between normal and hypertrophied-failing cardiac muscles with regard to the regulation of ionic balance.

Animals↗

PubMed2004

Modeling extracellular space electrodiffusion during Leão's spreading depression.

Computational modeling of spreading depression (SD) has been used increasingly to study the different mechanisms that are involved in this phenomenon. One of them that is still under discussion involves the mechanisms that originate the extracellular electrical field responsible for the dc potential shift. The main goal of this paper is to present a mathematical derivation for the extracellular electric field that is incorporated in a SD model that has the basic structure of Tuckwell and Miura's model, but with the ionic variations calculated electrochemically. Electrodiffusion equations were used to describe the ionic movement of the four ions Na+, K+, Cl-, and Ca2+. These are mutually coupled by the electric field within the extracellular space (ECS). The results from the simulations show that the model is able to calculate the effect of the ionic changes along the ECS on the electric field, and to reproduce the SD in respect to the most important features that characterize the phenomenon experimentally in the retina or hippocampus. It is suggested that the extracellular negative field-potential shift during SD is due to an electrical field generated by a Goldman-Hodgkin-Katz equation acting within the ECS.

Action Potentials↗

PubMed2006

Wild-type huntingtin participates in protein trafficking between the Golgi and the extracellular space.

Huntington disease (HD) is an autosomal dominant neurodegenerative disease caused by an expanded CAG trinucleotide repeat in the first exon of the HD gene, which results in a toxic polyglutamine stretch within huntingtin, the protein it encodes. Understanding the normal function of this essential protein is vital to understanding the root of the disease, yet despite more than a decade of investigation, its role in the cell remains elusive. Identifying the subcellular localization of huntingtin and understanding its effects on global gene expression are critical to this endeavor. While most reports agree that huntingtin is predominantly a cytoplasmic protein, conflicting distribution patterns have been demonstrated at the subcellular level. Here, we examine wild-type huntingtin's localization in cultured cells by expressing the full-length human protein tagged with enhanced green fluorescent protein (EGFP) within its unspliced genomic context. In fibrosarcoma and neuroblastoma cells, huntingtin shows discrete punctate, perinuclear localization overlapping largely with the trans-Golgi and cytoplasmic clathrin-coated vesicles, implicating huntingtin in vesicle trafficking. To determine whether huntingtin is involved in trafficking a specific subset of proteins, we measured changes in global transcription levels in embryonic stem cells and neurons lacking huntingtin. Huntingtin null neurons exhibit a significant reduction in transcripts encoding proteins destined for the extracellular space, many of which are components of the extracellular matrix or involved in cellular adhesion, receptor binding and hormone activity. Together, these findings support a role for huntingtin in the intracellular trafficking of proteins required for the construction of the extracellular matrix.

Animals↗

PubMed1973

Cell membrane resorption in the rat exocrine pancreas cell after in vivo stimulation of the secretion, as studied by in vitro incubation with extracellular space markers.

Pancreatic secretion in the rat was stimulated in vivo by pilocarpine injection causing 90% of the storage granules to be discharged within 2 h. Incubation in vitro with [(14)C]sorbitol indicated that maximal ingestion of this extracellular space marker occurred 3 h after secretogogue injection. Morphological cell membrane measurements on cells with stimulated secretion revealed a simultaneous decrease in amount of membrane bordering the microvilli at the cell apex, lamellar processes, and infoldings present at the latero-basal face of these cells. In 3-h stimulated cells, having the average zymogen granule content characteristic for that phase of secretion, ferritin treatment in vitro showed that the infoldings and related fragmentation vesicles had ingested ferritin and could consequently be considered as being transport vehicles for redundant cell membrane. During stimulated secretion numerous vesicles and vacuoles appeared in the apical cytoplasm. Part of these structures were postulated to be related to the Golgi complex and were discussed in relation to secretory protein transport. Another part of these structures was assumed to have an endocytotic nature, although they never contained ferritin.

Animals↗

PubMed1998

Rifampin concentrations in various compartments of the human brain: a novel method for determining drug levels in the cerebral extracellular space.

Antimicrobial therapy for brain infections is notoriously difficult because of the limited extent of knowledge about drug penetration into the brain. Therefore, we determined the penetration of rifampin into various compartments of the human brain, including the cerebral extracellular space (CES). Patients undergoing craniotomy for resection of primary brain tumors were given a standard dose of 600 mg of rifampin intravenously before the operation. A microdialysis probe (10 by 0.5 mm) was inserted into the cortex distantly from the resection and was perfused with two different rifampin solutions. Rifampin concentrations in the CES were calculated by the no-net-flux method. Intraoperatively, samples were taken from brain tumor tissue, perifocal tissue, and normal brain tissue in the case of pole resections. Rifampin concentrations in the various samples were determined by using a bioassay with Sarcinea lutea. In the various compartments, rifampin concentrations were highest within tumors (1.37 +/- 1.34 microg/ml; n = 8), followed by the perifocal region (0.62 +/- 0.67 microg/ml; n = 8), the CES (0.32 +/- 0.11 microg/ml; n = 6), and normal brain tissue (0.29 +/- 0.15 microg/ml; n = 7). Rifampin concentrations in brain tumors do not adequately reflect concentrations in normal brain tissue or in the CES. Rifampin concentrations in the CES, as determined by microdialysis, are the most reproducible, and the least scattered, of the values for all compartments evaluated. Rifampin concentrations in all compartments exceed the MIC for staphylococci and streptococci. However, CES concentrations may be below the MICs for some mycobacterial strains.

Adult↗

PubMed1980

Ultrastructural studies of subependymal extracellular spaces in adult and neonatal rat brain.

Ultrastructural studies of the subependymal neuropil of the lateral ventricular wall in the adult rat reveal two different types of enlarged extracellular spaces which appear to be due to the presence of glycosaminoglycans. Focal irregular enlargements are more numerous and are distinguished by the presence of fibrillar material. The other network is characterized by uniform width, branching processes, and an electron density identical to vascular basement membranes. The origin of the extracellular material is not revealed by these studies, but a relationship is suggested between the focal dilatation and subependymal cells. The distinction of these spaces is emphasized by the study of neonatal brain and by the use of ruthenium red (RR). Focal dilatations are very prominent in the 10 day old rat, but they do not contain fibrillar material. An adult type basement membrane-like network is present at this time. In the adult rat the focal dilatation has great affinity for RR, but the second network is very sparsely stained. The RR affinity is not present in the 10 day old rat; however, by the 26th day, the affinity is almost as great as that of an adult. These findings are considered to enhance the concept of a separate origin, composition, and probable function of these two networks.

Animals↗