UMLS:C0011570 - FACTA Search

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Query: UMLS:C0011570 (depression)
172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The ionic mechanisms of amantadine-induced changes in membrane potential and automatic activity in guinea pig ventricular myocytes were studied using the suction-pipette whole-cell clamp method. While 25-100 microM amantadine decreased the action potential amplitude and duration, 200 and 400 microM amantadine lengthened the action potential duration and decreased the maximum diastolic potential with an appearance of diastolic depolarization and automaticity. In the presence of 25-100 microM amantadine, the preparations developed an afterpotential due to incomplete repolarization and a delayed afterdepolarization that eventually brought about triggered automaticity. The former type of afterpotential was abolished by tetrodotoxin (TTX) and the latter by Co2+. Spontaneous activity from the diastolic depolarization was also abolished by Co2+ but not by Cs+. Amantadine suppressed the calcium current to as much as half of the control at the concentrations used (25-200 microM). The drug also produced a depression of the inward rectifier K+ current. The outward current showing time-dependent decay was activated at the plateau voltages by concentrations lower than 100 microM, whereas the delayed outward K+ current was depressed by the drug in a concentration-dependent manner at more positive potentials. Amantadine activated the TTX-sensitive and TTX-insensitive inward currents on repolarization from depolarized states, without producing the transient inward current. These results indicate that the amantadine-induced diastolic depolarization and afterpotentials are caused by changes in multiple ionic currents and that, therefore, the drug can be used as a unique model for the study of arrhythmogenesis.
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PMID:Amantadine-induced afterpotentials and automaticity in guinea pig ventricular myocytes. 279 Dec 24

1. Electrophysiological recordings were made from an identified neuron, F1, in the isolated suboesophageal ganglionic mass of Helix aspersa. 2. Bath applied adenosine (AD) (60-600 nM) depressed the depolarisation induced in the cell F1 by bath or iontophoretically applied acetylcholine (ACh). L-Phenylisopropyladenosine (L-PIA) also depressed the ACh response but NECA had no depressive effect. This effect of AD or L-PIA is inhibited by 12 microM 8-phenyltheophylline and is believed to be mediated by an A1 receptor. 3. If the proportion of the excitatory ACh response that was carried by calcium ions was increased, the percentage depression of this modified response by AD was significantly greater. 4. There was a residual current evoked by ACh in high calcium/sodium free Ringer. This ACh induced current was antagonized by 3 mM cobalt or 50 microM verapamil suggesting that it was calcium mediated. This residual current was also completely abolished by 0.6 microM AD. 5. Lower bath concentrations of AD (0.6-6 nM) and L-PIA than caused the depression of the ACh response and also adenosine triphosphate (ATP) (0.7 microM) and alpha,beta-methylene ATP (0.6 microM), enhanced the ACh D response. The relative potencies of AD and its two analogues 5'-N-ethylcarboxamideadenosine (NECA) and L-PIA in causing this enhancement of the ACh response were: NECA greater than AD greater than L-PIA. This is the potency ranking described for an A2 receptor.
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PMID:An analysis of the adenosine receptors responsible for modulation of an excitatory acetylcholine response on an identified Helix neuron. 289 Apr 75

Sympathetic preganglionic neurons of the intermediolateral nucleus were identified by antidromic stimulation in the slice of the T2 or T3 segment of the cat spinal cord. In normal Krebs solution, the action potential of these neurons had a shoulder on the repolarization phase and was followed by a long-lasting afterhyperpolarization (AHP). The AHP had a fast and a slow component. Superfusion of the slice with noradrenaline (NA), 10-50 microM, resulted in depression of the shoulder on the repolarization phase of the action potential, in the appearance of an afterdepolarization (ADP), which was absent in control conditions, and in depression of the slow component of the AHP. These effects were present whether the membrane potential of the sympathetic preganglionic neurons was decreased, increased, or not changed by NA. A typical ADP had time to peak of 50 ms and decay time of 200-500 ms; the amplitude was variable and large ADPs could be suprathreshold, causing repetitive firing. The amplitude and duration of the ADP increased with NA concentration. The appearance of the ADP seemed to be independent of the depressant effect of NA on the slow AHP. The ADP was associated with a decrease in neuron input resistance and was voltage dependent, being depressed in nonlinear fashion by membrane hyperpolarization. The ADP decreased in amplitude or disappeared within a range of membrane potentials from -70 to -90 mV. The ADP was reversibly suppressed by the Ca-channel blocker cobalt (2 mM), by low Ca Krebs (0.25 mM), and by iontophoretic injection of ethyleneglycol-bis(B-aminoethyl-ether)-N,N'-tetraacetic acid into the cell. Increasing Ca concentration from 2.5 to 10.0 mM had no effect. The ADP was unaffected by tetrodotoxin, at a concentration blocking the Na spike, but was suppressed in Na-free medium, even when the Ca spike was prolonged by tetraethylammonium 20 mM. Changes in external K concentration from 3.6 to 2.5 or 10.0 mM did not change the ADP. Increasing intracellular Cl concentration or decreasing extracellular Cl concentration had no effect on the ADP. It is concluded that the ADP, evoked by NA, is due to an increase in membrane conductance involving Na and Ca ions, possibly a Ca-activated Na conductance. The ADP provides a mechanism with which NA may modulate sympathetic preganglionic neuron responsiveness to excitatory synaptic inputs.
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PMID:Noradrenaline-induced afterdepolarization in cat sympathetic preganglionic neurons in vitro. 303 11

In anesthetized spinal cats, perfusion of lumbosacral spinal cord with artificial CSF containing manganese (1.5-3.0 Mm/l) or cobalt (6.0 mM/l) ions, led to reversible suppression of negative dorsal root potentials (DRP), induced by stimulation of ipsilateral hindlimbs' afferent nerves. The depression of the DRP proceeded in connection with the depression of presynaptic inhibition of extensor monosynaptic reflexes induced with impulse volleys in the group I flexor muscle afferents. The depression of inhibition was not associated with changes in amplitudes of testing monosynaptic reflexes. The DRP is concluded to have a synaptic origin.
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PMID:[Suppression of the dorsal root potentials of the cat spinal cord by manganese and cobalt ions]. 341 29

The pathophysiology, clinical features, and management of cyanide toxicity are reviewed and sources of cyanide are listed. Cyanide is a deadly poison that is found in many foods and household and industrial products, including some that are readily available. Cyanide binds with cytochrome oxidase, the enzyme responsible for oxidative phosphorylation, and paralyzes cellular respiration. Because the tissues cannot use oxygen that is delivered, aerobic metabolism ceases. The signs and symptoms of cyanide poisoning reflect the extent of cellular hypoxia. Manifestations may include respiratory abnormalities (progressing from tachypnea and dyspnea to respiratory depression and apnea), hemodynamic instability, metabolic acidosis, and, possibly, local irritant effects after oral ingestion of cyanide. The mainstays of therapy are 100% oxygen and specific antidotes to cyanide. Sequential treatment with amyl nitrite by inhalation, intravenous sodium nitrite 3%, and intravenous sodium thiosulfate 25% is directed toward decreasing the amount of cyanide available for cellular binding. Nitrites convert hemoglobin to methemoglobin, which reacts with cyanide to form cyanomethemoglobin. Sodium thiosulfate serves as a source of sulfur groups, which are needed for conversion of cyanide to thiocyanate, a compound that is relatively less toxic and is excreted renally. Supportive care also is important. Cobalt EDTA, hydroxocobalamin, and aminophenols have also been used but are not considered standard treatments. Cyanide poisoning is a medical emergency that requires prompt recognition and immediate and aggressive treatment.
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PMID:Clinical features and management of cyanide poisoning. 353 Jun 15

A coincubation system composed of hepatocytes in primary monolayer culture and erythrocytes suspended in the culture medium was developed and used as a model for investigations of mechanisms of cyanide antidote action at the cellular level. Hepatocyte ATP was used as the cytotoxicity indicator. Treatment of rat hepatocytes in the coincubation system with KCN (1.0 mM) for 10 min at 37 degrees C selectively reduced hepatocyte ATP levels to 33 +/- 15% of control (no KCN added) levels. 4-dimethylaminophenol (DMAP), cobalt(II) chloride, sodium nitrite, sodium thiosulfate, or a combination of the last two antidotes added to the KCN-containing medium significantly reversed ATP depression and the response was concentration dependent. The relative effectiveness, on a molar basis, was estimated to be DMAP greater than CoCl2 much greater than NaNO2 congruent to Na2S2O3. NaNO2 and DMAP induced methemoglobin formation in the absence of cyanide and cyanmethemoglobin formation in its presence; erythrocytes were required in the medium for effectiveness. CoCl2 produced neither cyanmethemoglobin nor thiocyanate in appreciable quantities nor required erythrocytes for antagonism. Na2S2O3 converted cyanide to thiocyanate and reversed ATP depression without erythrocytes in the medium. The addition of erythrocytes increased these rates significantly and to a greater extent than albumin. The overall results are consistent with previously proposed modes of action for these antidotes. However, the enhancement in cyanide metabolism and ATP recovery with Na2S2O3 and erythrocytes in the system was unexpected and raises the possibility that erythrocytes may contribute to cyanide disposition and antagonism in vivo when this antidote is administered.
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PMID:Application of a hepatocyte-erythrocyte coincubation system to studies of cyanide antidotal mechanisms. 356 31

Intracellular recordings were performed in Cs-loaded sympathetic preganglionic neurons (SPNs) of the intermediolateral nucleus, identified by antidromic stimulation, in the slice of the T2 or T3 segment of the cat spinal cord. Loading the neurons with Cs resulted in broadening of the action potential, depression of the fast component of the afterhyperpolarization (AHP), and appearance of an afterdepolarization (ADP). A typical ADP in a Cs-loaded neuron had time to peak of 45-110 ms, half-decay time of 70-250 ms, and amplitude of 2-10 mV at membrane potentials between -60 and -70 mV and at a Ca and K concentration of 2.5 and 3.6 mM, respectively, in the superfusion medium. The ADP was associated with a decrease in neuron input resistance and increased in magnitude with hyperpolarization of the cell membrane. The relation between peak ADP amplitude and membrane potential was linear within the range of membrane potentials from -60 to -100 mV. The ADP was reversibly suppressed by the Ca-channel blocker cobalt (2 mM) or by low Ca Krebs solution (0.25 mM). Superfusion with BaCl2 (1.0 mM) or tetraethylammonium (TEA) (10-20 mM) caused an increase in amplitude of the ADP and an increase in action potential duration. Hyperpolarizing pulses, delivered during the course of the spike shoulder, resulted in a decrease of spike duration and ADP amplitude. The ADP was not affected by tetrodotoxin, at a dose blocking the Na-spike, and was enhanced, in association with an increase in action potential duration, when NaCl in the Krebs solution was replaced with choline chloride. Increasing intracellular Cl concentration or decreasing extracellular Cl concentration had no effect on the ADP. Changes in external K concentration from 3.6 to 10 or 0.36 mM increased and decreased, respectively, the amplitude of the ADP. In the absence of Cs, and ADP, with similar time course to that recorded in Cs-loaded SPNs, was recorded when CaCl2 was replaced by BaCl or NaCl was replaced by TEAC1. It is concluded that the SPN afterpotential includes a Ca-dependent inward current, in addition to the already described fast and slow outward K currents of the AHP.
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PMID:Afterdepolarization mechanism in the in vitro, cesium-loaded, sympathetic preganglionic neuron of the cat. 358 70

Muscarinically induced depressions of the shoulder in the falling phase as well as the after-spike-hyperpolarization and -depolarization of the action potential in the isolated sympathetic neurons of rabbits were mimicked by a novel peptide Ca channel blocker, omega-conotoxin (synthetic; 0.1-0.5 microM). Cobalt ions (0.1-2 mM) showed bidirectional effects on the shoulder, an early depression followed by a later prolongation, while they consistently induced depressions of other components. Organic Ca channel blockers, verapamil and D-600 (1-50 microM) and nifedipine (0.1-1 microM) appeared to have other effects as they rather caused a prolongation of the falling phase that was shortened by further application of acetylcholine.
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PMID:Effects of Ca antagonists on the action potential and their relationship to the muscarinic ACh actions in isolated sympathetic neurons of rabbits. 380 74

Implantation of cobalt-agar rods into the visual cortex of 16 adult rats induced in some of the animals epileptiform bioelectrical activity and provoked in all of them histological and histochemical changes in the region of the implantation (primary focus) as well as in some ipsilateral projection sites of the visual cortex (secondary foci). The changes within the secondary foci are demonstrated in the Corpus geniculatum laterale, pars dorsale (dLGN), by means of 18 histochemical and 5 histological methods. Together with the appearance of hyperactive and degenerating neurones combined with neuronophagy and diminution of the number of synapses a marked gliosis developed, especially an increase of microglia. The destruction of the tissue induced a depression of energy and transmitter metabolism and intensified lytic processes. This is confirmed by the decreased activities of LDH, SDH, GPDH, G6PDH, NAD(P)H-TR, GABA-T and GDH and the increased activity of acid phosphatase in the neuropil of the secondary foci. Single hyperactive nerve and glial cells were accented by high activities of those enzymes which had a reduced activity in the neuropil. Since in our experiments agar-rods without cobalt never induced histological or histochemical changes in subcortical grisea of the visual system, the secondary foci seem to result from the direct influence of the cobalt, migrating in the corticothalamic projection pathway and identifiable in the dLGN by the TIMM technique.
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PMID:[Morphologic and histochemical changes in the secondary focus following cobalt-induced epileptogenic bioelectrical activity of the visual cortex in the adult rat]. 393 55

A variety of chemical and electrophysiological evidence indicates that the onset of afterdischarge and the subsequent profound enhancement of spike broadening that occur in the bag cell neurons of Aplysia are related to an increase in adenosine 3',5'-monophosphate-(cAMP) dependent protein phosphorylation. We have now used a two-electrode voltage clamp to study the properties of isolated bag cell neurons in cell culture and their response to 8 benzylthio-cAMP (8BTcAMP) and N6-n-butyl 8BTcAMP. These membrane-permeant and phosphodiesterase-resistant cAMP analogs induce spontaneous discharge and spike broadening in both the intact bag cell cluster and isolated bag cell neurons in cell culture. The dominant inward current in these cultured cells was found to be the calcium current, Ica, which was abolished by Co2+ (20 mM) or Ni2+ (10 mM) and could be observed in Na+-free media. In a minority of cells (2 of 12), in normal ionic media, a transient inward current was observed that was unaffected by Co2+ and Ni2+ and probably represents a sodium current. The three characterized potassium currents, the delayed rectifying current IK, the calcium-dependent current IC, and the early transient current IA, distinguished by their differing pharmacological and voltage-activation properties, were present in all healthy cells. Three effects of the cyclic AMP analogs (0.5 mM) on the electrical properties of these cells were 1) the emergence of a region of negative slope resistance in the steady-state I-V relations, 2) a depression of the net sustained outward currents due to depolarizing commands, and 3) a marked reduction in IA. When outward currents had been largely suppressed using high concentrations of tetraethylammonium (TEA) ions (100-460 mM) no effects of the cyclic AMP analogs could be observed on peak inward currents using NA+ and Ca2+ or Ba2+ as carriers of inward current. At least part of these electrical effects of the cyclic AMP analogs could be accounted for by a depression of a delayed potassium current and the A current.
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PMID:A voltage-clamp analysis of currents underlying cyclic AMP-induced membrane modulation in isolated peptidergic neurons of Aplysia. 609 Jun 5

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