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PubMed1987

Barium spikes are generated in the spines of the sea urchin Diadema antillarum.

In the presence of calcium, Ba2+ ions, at concentrations as low as 1-2 mM, block the action potentials (a.p.'s) elicited by the electrical stimulation of the primary spines of Diadema antillarum. Lower concentrations of barium (0.1 mM) potentiate the a.p.'s recorded from spines equilibrated with Ca-Free artificial sea water (ASW). Exposure of the spines to a saturated solution of EDTA in Ca-free, unbuffered ASW reversibly blocks their electrical activity. Spines blocked by EDTA continue to generate a.p.'s following their equilibration with Ca-free ASW containing 1 mM of Ba2+ ions. The time course of the a.p.'s recorded from spines equilibrated with normal ASW is only slightly affected by the combined action of 15 mM of tetraethylammonium (TEA) and 5 mM of 4-aminopyridine (4-AP). In contrast, the duration of the a.p.'s recorded from spines blocked by EDTA and placed in 1 mM barium is markedly increased by the combined actions of TEA and 4-AP at the above concentrations. We conclude that the Ca-channels of the neurites present in Diadema spines are not, at least qualitatively, an exception with regard to their permeation by Ba2+. The blocking action of low concentrations of these ions, particularly in the presence of calcium, may be explained by the extremely high surface to volume ratio prevailing in neurites with a diameter of only less than 0.1-0.3 micron.

4-Aminopyridine↗
PubMed1995

Properties of slow early potassium current in neurons of snail Helix pomatia.

1. In isolated neurons of visceral ganglia of snail Helix pomatia a slow early outward current (IA) was studied using a two-microelectrode voltage clamp technique. 2. The time of activation and inactivation of IAS at -40 mV were 90-120 msec and 3-5 sec respectively. The removal of inactivation at -120 mV took 2-5 min. 3. The reversal potential of the IAS was about -80 mV in normal saline and was sensitive to the external potassium concentration, changing about 35 mV per fivefold change in potassium over the range from 4 to 20 mM. The results suggest that IA were due to K+. 4. The IA persisted in Ca2+ -free medium and in the presence of Ca2+ -channels blockers, e.g., Cd2+. 5. The IA were blocked by 1-10 microM extracellular 4-aminopyridine, 1 mM of tetraethylammonium ions, 1 mM of Ba2+, but one was resistant to 1 mM Cs+. 6. 4-aminopyridine had a dual effect on the IA. It blocked the normal current, and then appeared to increase the inactivated currents.

4-Aminopyridine↗
PubMed1988

Ba2+-induced ATP release from adrenal medullary chromaffin cells is mediated by Ba2+ entry through both voltage- and receptor-gated Ca2+ channels.

We have measured on-line the exocytotic secretion of ATP from adrenal medullary chromaffin cells induced by Ba2+ using a luciferin/luciferase assay. We have found that Ba2+-induced ATP release requires the entry of Ba2+ through either voltage- or receptor-gated Ca2+ channels. This conclusion is based on the observations that short preincubations with low concentrations of either nicotine or K+ greatly enhance Ba2+-induced ATP release and that this augmentation can be blocked with the nicotinic receptor antagonist, hexamethonium, and the Ca2+ antagonist, nifedipine, respectively. Moreover, both nicotine and K+ stimulate 133Ba2+ uptake, which in the case of K+ is inhibited by nifedipine. These results support the hypothesis that the cellular events leading to Ba2+-induced secretion coincide at least in part with the events leading to Ca2+-dependent exocytosis.

Adenosine Triphosphate↗
PubMed1988

Drug-induced and toxic granulomatous hepatitis.

The ability to induce granulomatous hepatitis has been attributed to numerous drugs; some sixty causative drugs have been culled from the literature for this review. Additionally, granulomas or granulomatoid lesions have resulted from occupational exposure to toxic substances (e.g. silica, copper sulphate, beryllium compounds), and particulate material from various therapeutic or diagnostic procedures (e.g. reactions to starch, talc, suture material, polyvinyl pyrrolidone, silicone, barium sulphate, thorium dioxide) or from intravenous drug abuse (e.g. talc). Clinically, patients with drug-induced or toxic granulomatous hepatitis may be asymptomatic. More frequently, the presentation is that of an acute febrile illness, with or without a rash and eosinophilia, followed by jaundice and biochemical evidence of hepatic dysfunction. The diagnosis of drug-induced granulomatous hepatitis is based largely on ruling out other aetiologies. Liver biopsy plays a key role in diagnosis. Recovery is the rule following withdrawal of the drug. Morphologically, drug-induced granulomas may be impossible to distinguish from those due to other causes. Associated lesions suggesting a drug aetiology include significant tissue eosinophilia, unicellular hepatocytic degeneration and necrosis, cholestasis and acute cholangitis or vasculitis. Special stains, polarizing and phase contrast microscopy, transmission and scanning electron microscopy and energy dispersive X-ray microanalysis all play a role in the aetiologic diagnosis of some types of granulomas.

Chemical and Drug Induced Liver Injury↗
PubMedDate not supplied

Currents in the presynaptic terminal arbors of barnacle photoreceptors.

We have described the currents flowing across the presynaptic membranes of the four median photoreceptors of the giant barnacle, Balanus nubilus, using a quasi-voltage clamp arrangement. Membrane potential, measured in the terminal region of one photoreceptor, was controlled in all four terminals by feedback current supplied through the nerve containing the photoreceptors' axons. The [Ca2+]o in the saline was reduced to decrease the Ca2+ current, enabling better voltage control, and tetraethylammonium ion (TEA, 20 mM) was added to block a fast voltage-dependent K+ conductance. Depolarizing voltage steps from the resting potential in the dark (-60 mV) evoked slow, inward Ca(2+)-dependent currents which could be blocked by Co2+, Mg2+, or Cd2+. The Ca2+ currents were followed by large outward currents that persisted for many seconds after the offset of moderate or large pulses. These tail currents increased in magnitude and duration with pulse duration and reversed at about -80 mV, consistent with previous evidence for a Ca(2+)-activated K+ conductance in this membrane. When the Ca(2+)-activated outward current was reduced to zero by increasing the [K+]o so as to set EK at -20 mV, and then stepping the voltage to this value, the step evoked a steady inward Ca2+ current. Thus, the Ca2+ current did not show voltage- or Ca(2+)-dependent inactivation. When Ba2+ was substituted for Ca2+, 500-ms depolarizing steps evoked steady inward currents but no outward currents. In any given experiment, the activation voltage of the Ca2+ or Ba2+ current did not depend on holding potential. At the barnacle photoreceptor's synapse, the postsynaptic cell adapts to maintained presynaptic voltage by a mechanism that is not understood. We conclude that neither Ca2+ current inactivation nor a shift in activation voltage with holding potential can account for this adaptation.

Adaptation, Physiological↗
PubMed1987

Pharmacological characterization of the serotonin-sensitive potassium channel of Aplysia sensory neurons.

The effects of a variety of K+ channel blockers on current flow through single serotonin-sensitive K+ channels (the S channels) of Aplysia sensory neurons were studied using the patch-clamp technique. Tetraethylammonium (TEA), 4-aminopyridine (4-AP), and Co2+ and Ba2+ were first applied to the external membrane surface using cell-free outside-out patches. At concentrations up to 10 mM, these agents had little or no effect on single S-channel currents. At higher concentrations, external TEA acted as a fast open-channel blocker, reducing the single-channel current amplitude according to a simple one-to-one binding scheme with an apparent Kd of 90 mM. Blockage by external TEA is voltage independent. Internal TEA also acts as an open-channel blocker, with an apparent Kd of approximately 40 mM and a relatively weak voltage dependence, corresponding to an apparent electrical distance to the internal TEA-binding site of 0.1. Both internal and external TEA block the open channel selectively, with an affinity that is 10-100-fold greater than the affinity for the closed channel. Internal Ba2+ acts as a slow channel blocker, producing long closures of the channel, and binding with an apparent Kd of approximately 25-30 microM. These results show that single S-channel currents share a similar pharmacological profile with the macroscopic S current previously characterized with voltage clamp. On the basis of these results, a structural model for S-channel opening is proposed.

4-Aminopyridine↗
PubMed1967

Effects of tetrodotoxin on excitability of squid giant axons in sodium-free media.

The effect of tetrodotoxin on excitability of internally perfused squid giant axons immersed in various sodium-free media was examined. Action potentials were found to be suppressed by this substance, with or without sodium ion in the external medium. Tetrodotoxin showed a strong suppressive effect upon action potentials produced in media containing salts of only divalent cations (CaCl(2), CaBr(2), SrCl(2), or BaCl(2)). Our findings concerning the action of tetrodotoxin do not support the separate-channel hypothesis for excitable membranes.

Animals↗
PubMed2002

The role of radiological imaging in the diagnosis of acute appendicitis.

Several strategies have been employed to improve the accuracy of the diagnosis of appendicitis and to reduce the associated perforation rate. Because clinical algorithms have been disappointing, many physicians resort to radiological modalities. Plain abdominal x-rays are nonspecific, barium enema examination has relatively low accuracy, scintigraphy scans require considerable time and are difficult to interpret, and magnetic resonance imaging is relatively unstudied. The most promising modalities are graded compression sonography and computed tomography. In expert hands, these techniques can achieve a high degree of accuracy. Nevertheless, most published studies have been marred by methodological difficulties. Moreover, ultrasound is more useful in detecting than in ruling out appendicitis. The radiological criteria for acute appendicitis, the accuracy of various imaging modalities and the limitations of the available research are described.

Acute Disease↗
PubMed2005

Colorectal cancer prevention.

Colorectal cancer is the second leading cause of mortality in the United States. In the United States, the cumulative lifetime risk of developing colorectal cancer for both men and women is 6%. Despite advances in the management of this disease, the 5-year survival rate in the United States in only 62%. Because only 38% of patients are diagnosed when the cancers are localized to the bowel wall, it is likely that widespread implementation of screening could significantly improve the outcome. Colorectal cancer screening is cost effective, irrespective of the methods used. In addition to currently available methods (fecal occult blood, flexible sigmoidoscopy, colonoscopy, and double contrast barium enema), computed tomographic colonography (virtual colonoscopy) and stool-based molecular screening are under development. Four classes of chemopreventive compounds have demonstrated efficacy in reducing recurrent colorectal adenomas and/or cancer in randomized, controlled trials. They are selenium, calcium carbonate, hormone replacement therapy, and nonsteroidal anti-inflammatory drugs. The mechanisms of action of nonsteroidal anti-inflammatory drugs include inhibition of the cyclooxygenase system as well as cyclooxygenase-independent effects. Considerable effort is being expended to define chemopreventive activity, optimal dose, administration schedule, and toxicity for the coxibs in adenoma recurrence prevention trials. The threshold for tolerating toxicities is very low in asymptomatic individuals at minimally increased risk for colorectal neoplasia.

Adenomatous Polyps↗
PubMed2002

[IR spectra of dicarboxylate of alkali-earth metal].

The IR spectra of thirty dicarboxylates of alkali-earth metal have been investigated. It was found that carboxylates of different metal ion have different coordinate structure. Chelate structure prevails in carboxylates of Mg, Sr and Ba. Both chelate structure and bridge structure appear in carboxylates of Ca and Zn. The kind of acid was found to have no effect on the coordinate structure of carboxylate. Through melting the sebacates different kinds of coordinate structure changes can be observed. The Mg salt changes from chelate to bridge and Ca salt becomes inter-molecular chelate form insteat of in-molecular bridge, the structure of Se and Ba salt keep same as before.

Barium↗
PubMed1989

[A single calcium channel with anomalous rectification in mollusk neurons].

The patch clamp technique was used to examine the properties of an inward-rectifying potassium channel in the cell membrane of freshwater mollusc Planorbarius corneus neurons. Inward currents of single channels were observed at potentials more negative than potassium equilibrium potential (EK), when microelectrode contained potassium ions (50 mmol/l) and potassium channel blockers: tetraethylammonium, barium or cesium ions (10-20 mmol/l). The conductance of the single channel was equal to 81 +/- 12 pS at 50 mmol/l potassium ion concentration in the patch electrode. At potentials more positive than EK the conductance sharply decreased to 0 pS. The times of the open state of the closed one of the channel and probability of the open state existing for the ionic channel were estimated with various constant potentials. It was revealed that the channel openings were grouped in bursts. The lifetime of the open state and burst duration decreased with hypopolarization of the patch.

Action Potentials↗
PubMed1981

[Increase in the after-depolarization of a single node of Ranvier of isolated nerve fibers after application divalent (Ca2+, Ba2+, Mn2+, Zn2+, Ni2+) and trivalent (La2+) ions].

It has been shown that a 5.5-fold increase in Ca2+ concentration in the external solution leads to the rise in negative after depolarization (NAD) of a single node of Ranvier of myelinated nerve fibres isolated from Rana ridibunda. The NAD amplitude and duration increase 1.3-fold and 1.6 fold, respectively. Introduction in the external solution of Ba2+ and Mn2+ (up to 10 mM) leads to a negligible increase in NAD. A more pronounced effect on action potential and NAD of the node of Ranvier is exerted by Zn2+ and Ni2+ (1.5 and 10 mM), entailing a 5-fold and 10-fold increase in NAD duration. Combined action of Ni2+ and tetraethylammonium brings about a depolarization plateau lasting 50-150 ms followed by the development of NAD lasting 14-30 ms. Introduction in the external solution of La3+ produces a 3--7-fold increase in NAD. Under all exposures cited the decrease in NAD in exponential in character, as is the case in normal Ringer's solution. The changes in NAD described are likely to be accounted for by the effect of the ions on the time constants of the processes of activation and inactivation.

Action Potentials↗
PubMed1994

Adenosine decreases action potential duration by modulation of A-current in rat locus coeruleus neurons.

The possibility that adenosine modulates voltage-dependent conductances in locus coeruleus neurons was investigated in current-clamp and voltage-clamp experiments in a totally submerged rat brain slice preparation. Adenosine (100 microM) reduced the duration of control action potentials and action potentials prolonged by 1 mM barium. Adenosine (100 microM) also reduced the amplitude and slightly reduced the duration of TTX-resistant "calcium" action potentials. Action potential duration was also reduced by the adenosine receptor agonist 2-chloroadenosine in a concentration-dependent manner and the adenosine-induced reduction of action potential duration was blocked by the adenosine receptor antagonist 8-(p-sulfophenyl)theophylline, indicating that this action of adenosine is mediated by an adenosine receptor. The adenosine-induced reduction of action potential duration persisted in the presence of externally applied tetraethylammonium ion (6 mM) and cesium (3 mM). By contrast, adenosine did not reduce the duration of the action potential in the presence of 500 microM 4-aminopyridine (4-AP). Furthermore, 4-AP (30 microM) blocked the adenosine-induced reduction of action potential duration recorded in the presence of 1 mM barium. These data suggested that adenosine may be acting on the voltage-dependent, 4-AP-sensitive potassium current, IA. Single-electrode voltage clamp was used to study IA directly. IA was activated by depolarizing voltage pulses from a hyperpolarized holding potential and was blocked by 1 mM 4-AP. Adenosine (300 microM) enhanced IA by shifting the steady-state inactivation curve in the depolarizing direction.(ABSTRACT TRUNCATED AT 250 WORDS)

4-Aminopyridine↗
PubMed1997

Iron deficiency anaemia in general practice: presentations and investigations.

Twenty-six patients over the age of 50 years with proven iron deficiency anaemia were identified, investigated and followed up in general practice over a five-year period. The anaemia was symptomatic in 50% of patients but only 20% had symptoms related to the gut. Faecal occult blood testing was positive in five patients only and negative tests occurred in three patients with significant disease, including one caecal carcinoma. All patients agreed to oesophagogastroduodenoscopy (OGD) and fibreoptic sigmoidoscopy carried out on the same occasion. In eight patients, significant abnormalities were found on OGD and in two patients on sigmoidoscopy. Four patients declined barium enema examinations, two of whom had significant OGD abnormalities. Barium enema examination of the other 22 patients showed polyposis of the colon and a caecal carcinoma and initially missed one carcinoma of the caecum which was found subsequently. The likelihood of finding significant disease in iron-deficient patients over 50 years of age is high and should be assumed to be due to blood loss into the gut. Investigation by OGD, sigmoidoscopy and barium enema in the first instance seems warranted and is a condition that can be safely managed by the GP.

Aged↗
PubMed1994

A tetraethylammonium-insensitive inward rectifier K+ channel in Müller cells of the turtle (Pseudemys scripta elegans) retina.

Ion channels present in isolated glial (Müller) cells from the retina of the turtle (Pseudemys scripta elegans) were studied with the patch clamp technique. The predominant conductance in these cells was due to an inward rectifying potassium current. The whole-cell conductance of the inward rectifier was 20.2 +/- 1.9 nS (n = 7 cells) in a standard extracellular saline solution (3 mM extracellular potassium). This conductance was dependent on the extracellular potassium concentration, with a 2.88-fold change in conductance per tenfold shift in concentration. The relative permeability sequence to potassium of the inward rectifier was found to be: potassium (1.0) > rubidium (0.7) > ammonium (0.2) > lithium (0.1) = sodium (0.1), which corresponded to the Eisenman sequence IV or V for a strong-field-strength potassium binding site on the channel. The single channel conductance measured in cell-attached patches with potassium chloride (150 mM) in the pipette was 68.5 +/- 6.0 pS (n = 3 patches). The inward rectifier current was not blocked by extracellular tetraethylammonium (TEA+, 20 mM), but was blocked by extracellular barium (5 mM) or cesium (5 mM). The TEA+ insensitivity of the inward rectifier potassium channel in Müller cells is unusual, given that this type of channel in most excitable cells is sensitive to micromolar concentrations of this compound, and may be a characteristic of inward rectifier potassium channels that are primarily involved with extracellular potassium regulation.

4-Aminopyridine↗