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At least 1,441 records · Page 80Linked to original sources
PubMed1972

The effect of dehydroemetine on isolated guinea-pig atria.

1. The mechanisms of the inhibitory effect of dehydroemetine on the heart was investigated using spontaneously contracting isolated guinea-pig atria.2. In normal Locke solution, dehydroemetine caused a reduction in the rate and amplitude of contraction of the atria. The effect was antagonized by adrenaline and augmented by acetylcholine.3. Increasing the potassium concentration of the bathing medium increased the inhibitory effect of dehydroemetine on the atria, while decreasing the potassium concentration antagonized the effect of dehydroemetine.4. The character of the inhibitory effect of dehydroemetine on the atria altered when the sodium concentration of the bathing solution was lowered to 75.6 mmol. In the normal sodium medium arrest of beat by dehydroemetine was gradual; in the low sodium medium, it was abrupt.5. In the low, as in the normal sodium medium, the inhibitory effect of dehydroemetine was more marked the higher the potassium concentration of the bathing medium.6. In both standard Locke solution and Locke solution containing 75.6 mmol sodium, the effect of dehydroemetine closely mimicked that obtained by adding excess potassium to the solution.7. On the basis of the foregoing it was suggested that dehydroemetine acts by increasing the permeability of the myocardial cell membrane to potassium thereby leading to the accumulation of potassium in the extracellular space.

Acetylcholine↗
PubMed2002

Astrocyte modulation of neurotoxic injury.

Astrocytes produce trophic factors, regulate neurotransmitter and ion concentrations, and remove toxins and debris from the extracellular space of the CNS, maintaining an extracellular milieu that is optimally suited for neuronal function. Consequently, astrocytic functional impairments, as well as physiological reactions of astrocytes to injury have the potential to induce and/or exacerbate neuronal dysfunction. This mini-review showcases contemporary evidence provoking reformulation of concepts of the inter-dependence between astrocytes and neurons and advances several mechanisms used by astrocytes in potentiating or nullifying the final pathway of neuropathologic injury. Though clearly possessing an array of protective systems and upregulating a large number of protective molecules in response to xenobiotic exposure, recent evidence also invokes astrocytes in secondary amplification of cell injury in multiple neurodegenerative disorders.

Animals↗
PubMed1987

Retinal spreading depression and the extracellular milieu.

We used isolated chick retina in vitro to study the participation of the extracellular milieu in the occurrence and propagation of spreading depression. The propagation was followed by visual observation or microphotometry and the ionic changes in the extracellular compartment were recorded with double-barreled ion-selective microelectrodes. The front of the spreading wave is accompanied by increased light scattering in the tissue and by decrease of Cl-, Na+, and Ca2+, increase of K+, and an alkaline-acid shift in the extracellular space, concomitant with the slow voltage changes characteristic of the wave. As the spread is related to the chemical steady-state of the extracellular milieu, the velocity of propagation is influenced by a balanced interplay of the chemical constituents of the superfusing solution, e.g., K+, HCO-3, and glucose facilitate, while Cl- and Mg2+ hinder the wave. Steady-state alterations induced by physical factors (temperature) or related to experimental conditions (speed and direction of superfusate flow) change markedly the velocity of propagation. Generally the procedures that cause increase of velocity augment the susceptibility of the preparation to the reaction and eventually may trigger it. Propagated spreading depression is considered as a chemical diffusion reaction pervading more intensively the inner plexiform layer of the retina.

Animals↗
PubMed1977

Extracellular matrix synthesis in blastula and gastrula stages of normal and hybrid frog embryos. I. Toluidine blue and lanthanum staining.

Four developmental stages of Rana pipiens, R. pipiens female X R. catesbeiana female, and R. pipiens female X R. esculenta male embryos were fixed in standard electron microscopic fixatives with or without 1% lanthanum nitrate (LN) added. Embryos fixed without LN were embedded and sectioned at 0-5 micrometer and stained with toluidine blue. Embryos fixed with LN were embedded and sectioned at 70-80 nm and examined in the electron microscope. Both techiques show a dramatic increase in the amount of stainable material in the extracellular matrix during development. Blastula stage embryos have a small amount of material in the extracellular matrix. Early gastrulae have more stainable material than blastulae and this increased amount appears to be due to an accumulation of material in the marginal zone of the embryo, especially near the dorsal lip of the blastopore. Late gastrulae have large amounts of stainable material in the extracellular spaces in almost all parts of the embryo. Interspecific arrested hybrid embryos do not show the same dramatic accumulation of stainable material in their extracellular matrices.

Animals↗
PubMed1978

Extravascular transfer within the anuran pars intermedia.

To study the transport of protein from the blood into and throughout the sparsely vascularized pars intermedia of anurans, the electrondense tracer, horseradish peroxidase (HRP) was injected into the vascular system of adult frogs. A strong reaction product was localized in small vesicles in the cytoplasm of that portion of the stellate cells immediately beneath the vascular spaces. Also, within two minutes after an injection of HRP, which was given during a period of one minute, the reaction product was seen in the extracellular spaces between the stellate and/or MSH secretory cells throughout the gland. Additionally, it appeared that HRP was pinocytosed by the stellate cell processes in the interior of the pars intermedia. Since frogs adapted to different backgrounds were perfused with HRP for a variety of time periods, from 3 to 90 min, it was thought that it would be possible to trace the pathway of the HRP-filled vesicles as they moved through the stellate cells. There did not appear to be a migration of these vesicles within the cells. Because of the electron density of the HRP, the tortuous extensions from the perivascular spaces of the capillary plexus intermedius were obvious as they ramified into the pars intermedia and pars nervosa. In the frogs not injected with HRP, it was possible to observe the substructure of these ramifications which paralleled the stellate cells and formed enlargements at the convergence of the stellate cell processes and sometimes the nerve processes. An extravascular, many-branched transport system that penetrates the parenchyma is discussed in addition to the possible transfer role of the stellate cells.

Animals↗
PubMed2002

Neuroprotective effects of increased extracellular Ca(2+) during aglycemia in white matter.

We investigated the effects of extracellular [Ca(2+)] ([Ca(2+)](o)) on aglycemia-induced dysfunction and injury in adult rat optic nerves. Compound action potentials (CAPs) from adult rat optic nerve were recorded in vitro, and the area under the CAP was used to monitor nerve function before and after 1 h periods of aglycemia. In control artificial cerebrospinal fluid (ACSF) containing 2 mM Ca(2+), CAP function fell after 29.9 +/- 1.5 (SE) min and recovered to 48.8 +/- 3.9% following aglycemia. Reducing bath [Ca(2+)] during aglycemia progressively improved recovery. For example, in Ca(2+)-free ACSF, the CAP recovered to 99.1 +/- 3.8%. Paradoxically, increasing bath [Ca(2+)] also improved recovery from aglycemia. In 5 or 10 mM bath [Ca(2+)], CAP recovered to 78.8 +/- 9.2 or 91.6 +/- 5.2%, respectively. The latency to CAP failure during aglycemia increased as a function of bath [Ca(2+)] from 0 to 10 mM. Increasing bath [Mg(2+)] from 2 to 5 or 10 mM, with bath [Ca(2+)] held at 2 mM, increased latency to CAP failure with aglycemia and improved recovery from this insult. [Ca(2+)](o) recorded with calcium-sensitive microelectrodes in control ACSF, dropped reversibly during aglycemia from 1.54 +/- 0.03 to 0.45 +/- 0.04 mM. In the presence of higher ambient levels of bath [Ca(2+)] (i.e., 5 or 10 mM), the aglycemia-induced decrease in [Ca(2+)](o) declined, indicating that less Ca(2+) left the extracellular space to enter an intracellular compartment. These results indicate that the role of [Ca(2+)], and divalent cations in general, during aglycemia is complex. While extracellular Ca(2+) was required for irreversible aglycemic injury to occur, higher levels of [Ca(2+)] or [Mg(2+)] increased the latency to CAP failure and improved the extent of recovery, apparently by limiting Ca(2+) influx. These effects are theorized to be mediated by divalent cation screening.

Action Potentials↗
PubMed1991

Mechanisms underlying the generation of cortical field potentials.

The generation of currents and potentials detectable in the space surrounding cellular elements within central nervous structures is described. The following aspects are especially taken into account: Generator structures, membrane potential changes of single neurons and of single glial cells, generation of potentials in the extracellular space, and types of cortical field potentials.

Cerebral Cortex↗
PubMed1988

Extracellular superoxide dismutase in the vascular system of mammals.

Plasma extracellular superoxide dismutase (EC-SOD) from the pig, cat, rabbit, guinea pig and mouse was found to be heterogeneous with regard to heparin affinity and could be separated into three fractions: A without affinity, B with weak affinity and C with relatively high affinity. Rat plasma EC-SOD was deviant and contained only A and B fractions. There were very large interspecies differences in total plasma EC-SOD activity and in division of the activity between the different fractions. Intravenous injection of heparin resulted in the pig, dog, cat, rabbit, guinea pig and mouse in a prompt increase in the plasma SOD activity. The increase was due to release of EC-SOD C to plasma, most probably from endothelial cell surfaces. In the rat, heparin induced no increase in plasma SOD activity, apparently because of the absence of EC-SOD C in this species. The relative heparin-induced increase in plasma EC-SOD C varied between 2 and 11 in the different species and was distinctly correlated with the heparin affinity of EC-SOD C in the particular species. Apparently the EC-SOD C, present in the vasculature, forms an equilibrium between plasma and endothelium, whereas EC-SOD A and B primarily exist in plasma. The wide diversity of EC-SOD in the vascular system of mammals with regard to total amount, division into fractions and distribution between plasma and endothelium indicates that the pathogenic potential of superoxide radicals in the extracellular space might vary much between species.

Affinity Labels↗
PubMed1994

Light-dependent hydration of the space surrounding photoreceptors in chick retina.

PURPOSE: To characterize the light-evoked increase in the volume (or hydration) of the subretinal space (SRS) of chick retina and to investigate its retinal pigment epithelial (RPE) origin. METHODS: The authors perfused chick retina-RPE-choroid preparations with the extracellular space marker, tetramethylammonium (TMA+), and estimated its concentration ([TMA+]o) using double-barreled, ion-selective electrodes. They recorded dark-light changes in subretinal [TMA+]o and studied the effects of drugs that suppress RPE ion transport and conductances. RESULTS: The authors observed a slow, light-evoked decrease in subretinal [TMA+]o, about 7% in amplitude, that slowly returned to baseline and then increased at light OFF. It was 40% to 65% inhibited by bumetanide and furosemide, known to inhibit RPE apical membrane Na-K-Cl cotransport; 70% to 80% inhibited by DIDS, an inhibitor of RPE basal membrane chloride conductance, and 50% inhibited by 0.5 mM BaCl2, a blocker of the K+ conductance of the RPE apical membrane. Decreases in subretinal [TMA+]o also were produced when the authors lowered [Cl-]o or [K+]o in the SRS by reducing concentrations in the retinal perfusate. The effect on [TMA]o was larger for [Cl-]o than for [K+]o and was inhibited by bumetanide and DIDS. CONCLUSIONS: Changes in subretinal ion concentrations in light and darkness, most likely [K+]o, modify SRS hydration by modulating RPE apical membrane Na-K-Cl cotransport, as well as the conductive effluxes of K+ across the apical membrane and Cl- across the basal membrane. These changes depend principally on the movement of water into or out of the RPE. In turn, subretinal hydration modifies local ion concentrations and the composition of the interphotoreceptor matrix.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1992

Extracellular changes of inorganic phosphate are different during spreading depression and global cerebral ischemia of rats.

Tissue levels of inorganic phosphate (iP-) and lactate (lac) increase during cerebral ischemia and cortical spreading depression (SD). Since cell membranes become leaky during these insults, iP- and lac were expected to leak into the extracellular space (ECS). In order to find out whether this occurs or does not, a microdialysis (MD) fiber was implanted into the cortex of anesthetized rats and extracellular lactate (lac(e)) and extracellular iP- (iPe-) were determined during various insults. Extracellular lactate increased to about the same extent during ischemia and SD. In contrast, iPe- increased during ischemia but not during SD. Instead, iPe- started to rise after SD and reached its maximum about 45 min later. The distinct pattern of iPe- in comparison to lac(e) during the above mentioned insults points to a qualitative difference of the underlying mechanisms: whereas lac appears within the ECS at any stressful situation, elevation of iP- within the ECS indicates depletion of energy stores in parallel to the lack of control of ion homeostasis.

Animals↗
PubMed2006

Changes in diffusion parameters, energy-related metabolites and glutamate in the rat cortex after transient hypoxia/ischemia.

It has been shown that global anoxia leads to dramatic changes in the diffusion properties of the extracellular space (ECS). In this study, we investigated how changes in ECS volume and geometry in the rat somatosensory cortex during and after transient hypoxia/ischemia correlate with extracellular concentrations of energy-related metabolites and glutamate. Adult male Wistar rats (n = 12) were anesthetized and subjected to hypoxia/ischemia for 30 min (ventilation with 10% oxygen and unilateral carotid artery occlusion). The ECS diffusion parameters, volume fraction and tortuosity, were determined from concentration-time profiles of tetramethylammonium applied by iontophoresis. Concentrations of lactate, glucose, pyruvate and glutamate in the extracellular fluid (ECF) were monitored by microdialysis (n = 9). During hypoxia/ischemia, the ECS volume fraction decreased from initial values of 0.19 +/- 0.03 (mean +/- S.E.M.) to 0.07 +/- 0.01 and tortuosity increased from 1.57 +/- 0.01 to 1.88 +/- 0.03. During reperfusion the volume fraction returned to control values within 20 min and then increased to 0.23 +/- 0.01, while tortuosity only returned to original values (1.53 +/- 0.06). The concentrations of lactate and glutamate, and the lactate/pyruvate ratio, substantially increased during hypoxia/ischemia, followed by continuous recovery during reperfusion. The glucose concentration decreased rapidly during hypoxia/ischemia with a subsequent return to control values within 20 min of reperfusion. We conclude that transient hypoxia/ischemia causes similar changes in ECS diffusion parameters as does global anoxia and that the time course of the reduction in ECS volume fraction correlates with the increase of extracellular concentration of glutamate. The decrease in the ECS volume fraction can therefore contribute to an increased accumulation of toxic metabolites, which may aggravate functional deficits and lead to damage of the central nervous system (CNS).

Animals↗
PubMed2004

Structural and functional consequences of loricrin mutations in human loricrin keratoderma (Vohwinkel syndrome with ichthyosis).

Although loricrin is the predominant protein of the cornified envelope (CE) in keratinocytes, loss or gain of loricrin function in mouse models produces only modest skin phenotypes. In contrast, insertional mutations resulting in a frameshift in the C-terminal domain of loricrin produce the characteristic ichthyosis of loricrin keratoderma in mouse and man. To ascertain the basis for the loricrin keratoderma phenotype, we assessed epidermal structure and stratum corneum (SC) function in a previously genotyped human loricrin keratoderma kindred. Our studies revealed abnormal corneocyte fragility and basal permeability barrier function, but accelerated repair kinetics. Despite fragility, increased water loss occurred predominantly via extracellular domains, which correlated with disorganized lamellar bilayers that were linked spatially to discontinuities of the CE. Accelerated barrier recovery was explicable by amplified lamellar body secretion, while partial normalization of the CE in the outer SC correlated with persistence of abundant calcium in the extracellular spaces (positioned to activate transglutaminase-1). These results show that the barrier abnormality in loricrin keratoderma is linked to a defective CE scaffold, resulting in increased extracellular permeability, as shown previously for another "scaffold disorder", lamellar ichthyosis. But in contrast to lamellar ichthyosis, the CE scaffold partially normalizes in the outer SC in loricrin keratoderma.

Adolescent↗
PubMed1977

The pituitary of Aphanius dispar (Rüppell) from hypersaline marshes and freshwater. II. Ultrastructure of the rostral pars distalis.

An ultrastructural study of the rostral pars distalis of the pituitary of Aphanius dispar specimens taken from freshwater or hypersaline marshes revealed significant structural differences which indicate higher activity of the prolactin cells in the hypotonic medium. Prolactin cells from freshwater specimens had larger secretory granules, a higher amount of endoplasmic reticulum, and expanded intercellular spaces with many secretory lakes. These cells contained an unusual cytoplasmic structure, consisting of twisted canals with vesicular lumina, connected to the endoplasmic reticulum of the cell. This structure is about 1-2 micron in diameter. Stellate cells are characterized by extracellular spacing junctions which are particularly noticeable at the confluence of the interstellate cell canaliculi and the pericapillary space.

Animals↗
PubMed1975

Is there a blood-brain barrier at the optic nerve head?

The retina and optic nerve have been demonstrated to possess a blood-brain barrier that prevents the passive passage of protein and certain dyes from the blood vessels into the extracellular space. Our observations suggest that an exception is present at the normal optic disc. Using horseradish peroxidase as a tracer for electron microscopy and the normal rhesus monkey as the experimental animal, we have demonstrated that in certain regions of the optic nerve head, horseradish peroxidase from the blood stream reaches the axons of the optic nerve through the border tissue of Elschnig from the adjacent choridal tissues. A barrier formed by a series of cell junctions between glial cells at the edge of the optic disc prevented spread of the tracer from the optic disc into the subretinal space.

Animals↗
PubMed1994

Cytoplasmic Ca2+ determines the rate of Ca2+ entry into Mardin-Darby canine kidney-focus (MDCK-F) cells.

Transformed Mardin-Darby canine kidney-focus (MDCK-F) cells exhibit spontaneous Ca2+ oscillations from an inositol 1,4,5-triphosphate-sensitive cytoplasmic Ca2+ store. In this study, Ca2+ entry from the extracellular space and its role in generation of oscillations were investigated by means of Ca2+ video imaging and the Fura-2/Mn2+ quenching technique. Oscillations were dependent on extracellular Ca2+ concentration and were inhibited by extracellularly applied La3+, Co2+ and Ni2+. Depolarization of the cell membrane with high K+ concentrations and the L-type Ca2+ channel blocker nifedipine had no effect on oscillations, indicating the lack of involvement of voltage-gated Ca2+ channels. Mn2+ quenching experiments disclosed significant Ca2+ influx into MDCK-F cells. The rate of this influx was constant between Ca2+ spikes, but markedly increased during the spontaneous Ca2+ spikes. Similar transient increases in Ca2+ entry could be mimicked by agents triggering intracellular Ca2+ release such as bradykinin and thapsigargin. We conclude that the plasma membrane of MDCK-F cells exhibits a marked voltage-independent Ca2+ permeability permitting Ca2+ entry into the cytoplasm. The rate of Ca2+ entry which determines the frequency of oscillations is most likely to be regulated by the cytoplasmic Ca2+ concentration.

Animals↗
PubMed1992

Endogenous extracellular glutamate accumulation in rat neocortical cultures by reversal of the transmembrane sodium gradient.

Glutamate excites receptors located on neurons that cause calcium and sodium influx involved in excitatory synaptic transmission. During ischemia, excess glutamate is present in the extracellular space of brain tissue, leading to abnormal levels of calcium influx and eventually to cell death. In mixed neuronal/glial cell cultures we have found that reduction of extracellular sodium concentration below approximately 10 mM causes marked increases in glutamate and aspartate in medium collected 10 min after changing to low sodium. Various data indicate that the accumulated glutamate comes from reversal of normal cellular glutamate uptake, a process also thought to occur during ischemia.

Amino Acids↗
PubMed1999

Effect of alterations in extracellular norepinephrine on adrenoceptors: a microdialysis study in freely moving rats.

Chronic electroshock treatment (once daily for 12 days) increases extracellular norepinephrine in the frontal cortex and hippocampus as measured by microdialysis. This chronic treatment produced an elevation of basal norepinephrine overflow into extracellular space while both the first and the twelfth treatments produced a transient increase in norepinephrine overflow of about 40 min. Acutely, desmethylimipramine (10 mg/kg) treatment significantly increased extracellular norepinephrine. While chronic desmethylimipramine (once daily for 10 days) increased basal overflow of norepinephrine in the frontal cortex and hippocampus, the tenth daily administration of desmethylimipramine did not produce a statistically significant increase in extracellular norepinephrine. Both daily electroshock and daily desmethylimipramine produced down regulation of beta-adrenoceptors in the hippocampus and the frontal cortex. Chronic electroshock caused up regulation of alpha-adrenoceptors in the frontal cortex but not in the hippocampus while chronic desmethylimipramine administration did not alter alpha-adrenoceptors in either structure. Depletion of norepinephrine with reserpine or with 6-hydroxydopamine prevented the down regulation of beta-adrenoceptors while depletion of this neurotransmitter did not prevent the electroshock-induced up regulation of alpha-adrenoceptors in the frontal cortex. These data suggest that down regulation of beta-adrenoceptors is mediated through increases in extracellular norepinephrine. In contrast, up regulation of alpha-adrenoceptors appears to be independent of norepinephrine release and does not require the presence of noradrenergic neurons in order to be induced by electroshock.

Adrenergic Uptake Inhibitors↗