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

A novel application of voltage-sensitive dyes is described. Hippocampal slices in vitro accumulated voltage-sensitive cyanine dyes under conditions presumed to cause depolarization and hyperpolarization. Increasing extracellular potassium caused a depression of dye uptake that correlated linearly with the membrane potential calculated from the Goldman equation. Veratrine depressed dye uptake, and this effect was blocked by addition of tetrodotoxin or removal of extracellular sodium. Ouabain also depressed dye uptake. Conversely, hyperpolarizing conditions using reduced extracellular sodium caused increased dye uptake. These results support a voltage-dependent mechanism for the uptake of cyanine dyes in hippocampal slices. Application of this phenomenon as an alternative to 2-deoxyglucose autoradiography for mapping neuronal activity will be presented.
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PMID:A new method of monitoring membrane potential in rat hippocampal slices using cyanine voltage-sensitive dyes. 401 Mar 31

Amrinone, a positive inotropic-vasodilator agent, was administered to anaesthetised dogs in an attempt to reverse heart failure induced by drugs possessing negative inotropic properties. Propranolol, a beta-adrenergic blocker; verapamil, a calcium slow-channel blocker procainamide, a type 1 antiarrhythmic agent; or sodium pentobarbital, a barbituate; administered as a bolus injection and/or infusion, produced a sustained depression in canine cardiac function. Cardiac depression was characterised by a greater than 40% reduction in cardiac contractile force (CF) and maximum left ventricular pressure development (LV dp/dtmax), a 30 to 50% reduction in cardiac output (CO) and concomitant increases in mean central venous or mean right atrial blood pressures (CVP, RAP, respectively). Amrinone, when administered intravenously as a bolus injection (1 or 3 mg X kg-1) plus an infusion (0.03 or 0.1 mg X kg-1 X min-1) reversed the depression in cardiac function by increasing CF, CO and LV dp/dtmax and decreasing preload CVP or RAP in all four drug-induced failure models. Due to the vasodilator properties of amrinone, afterload, total peripheral resistance (TPR), was reduced in verapamil and procainamide failures as well as in propranolol failure, the only model where TPR increases. In another model of heart failure, in which ouabain-induced arrhythmias preceded procainamide toxicity, amrinone was also an effective cardiotonic agent. Ouabain's inotropic effect was studied in propranolol-induced heart failure. Although an increase in LV dp/dtmax and a decrease in CVP were noted, ouabain (40 micrograms X kg-1 iv) increased TPR and had little effect on the depression in CF and CO. Drug-induced models of heart failure were useful pharmacological tools for evaluating the cardiotonic agent's ability to overcome severe cardiac depression. In propranolol-, verapamil-, procainamide-, and pentobarbital-induced cardiac toxicity, amrinone could be of therapeutic value.
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PMID:The beneficial effect of amrinone on acute drug-induced heart failure in the anaesthetised dog. 404 15

1. The time dependence of the increase in amplitude (facilitation) of a second end-plate potential (e.p.p.) elicited within 10-100 msec of a preceding e.p.p. was examined at neuromuscular junctions in sartorius muscles of toads. Facilitation was defined by two characteristics, initial facilitation and the time constant of its exponential decay.2. The time constant of decay of facilitation was longer at lower temperatures and the Q(10) was 4.3 in the range 10-25 degrees C. There was no significant effect of temperature on initial facilitation.3. Ouabain (10(-4)-10(-3)M), lithium substitution for sodium, sodium azide (5 mM) and N-ethylmaleimide (NEM, 0.1 mM) initially had no effect on initial facilitation or the decay of facilitation. After some time, they all caused a longer time constant of decay of facilitation and a depression of initial facilitation.4. It was concluded that the decay of facilitation is not directly dependent on active transport of sodium ions, calcium efflux, ATP-dependent movements of calcium or mitochondrial uptake of calcium following an action potential.5. Ouabain, lithium, sodium azide, and NEM all caused an increase in transmitter release. This effect, and the late effects on facilitation, were thought to be due to an increase in intracellular calcium concentration in nerve terminals.6. No relationship was found between the quantal content of e.p.p.s (range, 0.8-100) and initial facilitation, or the time constant of decay of facilitation.7. Substitution of strontium for calcium ions caused a marked prolongation of the time constant of decay of facilitation, and a depression of initial facilitation.8. The results were consistent with the hypothesis that the time constant of decay of facilitation is related to the rate of disappearance of an ;active' complex of calcium (CaA) which, of itself, is not sufficient for transmitter release. It is suggested that an action potential produces CaA which decays with the time constant of facilitation and CaS, a short-life complex of calcium which decays with the time constant of the phasic release of transmitter. The release of transmitter is proportional to some function of [CaA] and [CaS].
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PMID:On facilitation of transmitter release at the toad neuromuscular junction. 415 79

1. Slices of rat cerebral cortex, incubated anaerobically at 37 degrees , lost K(+) from an initial concentration of 102m-equiv./kg. to a concentration of 57m-equiv./kg. after 10min. On subsequent aerobic incubation they regained K(+) rapidly at a rate that varied with the K(+) concentration of the medium. 2. Lower aliphatic alcohols, present at equal thermodynamic activity, produced approximately equal degrees of inhibition of K(+) uptake during the aerobic incubation. This inhibition was reduced by an increase in K(+) content of the medium. Ethanol did not affect the rate of K(+) loss during anaerobic incubation. 3. Li(+), in concentrations of 1-10mm, also inhibited K(+) uptake by brain-cortex slices, the degree of inhibition varying with the Li(+) concentration. Ouabain also inhibited K(+) uptake. 4. The same series of alcohols, at equal thermodynamic activity, produced comparable degrees of inhibition of Na(+),K(+),Mg(2+)-stimulated adenosine-triphosphatase activity in brain microsomes. 5. It is suggested that inhibition of cation transport is an important, but not a primary, mechanism in the production of central nervous depression by alcohols and other substances.
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PMID:Effects of lower alcohols on potassium transport and microsomal adenosine-triphosphatase activity of rat cerebral cortex. 422 75

1. Ouabain given by intracerebroventricular injection to mice in small doses (0.1-0.4 mug) produced a dose related depression of central nervous activity, characterized by a reduction in spontaneous locomotor activity, hypothermia, catalepsy and ptosis, lowered body posture and lack of response to external stimuli. Doses above 0.4 mug were excitatory, convulsant and lethal.2. The depressant effects could be antagonized by (+)-amphetamine, desmethylimipramine, dibutyryl cyclic 3'5'-adenosine monophosphate and caffeine.3. The MAO inhibitor nialamide produced only a small antagonism of ouabain, resulting in a greater rate of recovery from the depressant effects of ouabain.4. The depressant effects were associated with a marked elevation of whole-brain dopamine levels with little change in noradrenaline or 5-hydroxytryptamine.5. The dopamine-beta-hydroxylase inhibitor sodium diethyldithiocarbamate, administered by intracerebroventricular injection, produced effects qualitatively similar to those seen after ouabain.6. An interference with central transmitter function is postulated as a possible mode of action of intracerebroventricularly injected ouabain.
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PMID:Pharmacological properties of centrally administered ouabain and their modification by other drugs. 432 23

The ion permeability of the membrane junctions between Chironomus salivary gland cells is strongly depressed by treatments that are generally known to inhibit energy metabolism. These treatments include prolonged cooling at 6 degrees -8 degrees C, and exposure to dinitrophenol, cyanide, oligomycin, and N-ethylmaleimide. Intracellular injection of ATP appears to prevent depression of junctional permeability by dinitrophenol or to reverse it. Ouabain, azide, p-chloromercuriphenylsulfonic acid, reserpine, and acetazolamide fail to depress junctional permeability. Thus the ion permeability of the junctional membranes appears to depend on energy provided by oxidative phosphorylation. Possible energy-linked processes for maintaining junctional permeability are discussed, including processes involving transport of permeability-modifying species such as Ca(++).
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PMID:Permeability of a cell membrane junction. Dependence on energy metabolism. 577 20

Ouabain, tetrodotoxin, and calcium selective ionophore (A23187) were administered bilaterally into the hypothalamus of the unrestrained, fully conscious cat, while body temperature and other indicators of thermoregulatory responses were monitored continuously. Posterior hypothalamic microinjection of 2.0 to 10.0 ng or tissue perfusion with 1.1 X 10(-7) to 1.1 X 10(-8) M ouabain elicited dose dependent increases in body temperature accompanied by pinnae vasoconstriction, shivering and postural changes consistent with heat conservation. Tetrodotoxin, microinjected in doses of 0.5 and 5.0 ng or tissue perfusions with 7.8 X 10(-9) to 7.8 X 10(-7) M in the posterior hypothalamus elicited dose dependent falls in body temperature. However, tetrodotoxin microinjected into the anterior hypothalamic region elicited only increases in temperature. The calcium selective ionophore, A23187, at least at the concentrations used in this study, did not appear to produce any consistent effects on thermoregulation. These data support the hypothesis that the ionic milieu of the posterior hypothalamic region is essential in the maintenance of body temperature. Further, they suggest that increasing the [Ca++]/[Na+] acts in a manner similar to a depression in the firing frequency of a distinct population of cells, which may in turn determine in some way the "set-point" for body temperature. There is no evidence to support the concept that increasing the [Ca++]/[Na+] causes an increased release of the synaptic contents of the region.
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PMID:Alterations in body temperature elicited by intrahypothalamic administration of tetrodotoxin, ouabain and A23187 ionophore in the conscious cat. 624 80

Receptor-ligand interactions at the surface of the human neutrophil induce lysosomal enzyme release and the generation of O2.-, responses which are anteceded by changes in the membrane potential (delta psi) as measured by [3H]-triphenylmethylphosphonium ion distribution. Surface stimuli (immune complexes, concanavalin A) initiated a rapid (less than 10 s) hyperpolarization response by both normal and cytochalasin B-treated cells. Replacement of extracellular Na+ with either K+ or choline depressed O2.- generation and lysosomal enzyme release in neutrophils exposed to concanavalin A or immune complexes. Replacement of Na+ with K+ led to a substantial fall in resting membrane potential, whereas replacement of Na+ with choline did not. Thus, depression of O2.- generation and lysosomal enzyme release in Na+-free medium were specifically due to a lack of extracellular Na+ and not to depolarization of the membrane. Although it has been shown that extracellular Na+, and possibly an influx of Na+, is required for optimal neutrophil function, neither depolarization nor Na+ influx per se was sufficient to activate fully these cells, since the Na+ ionophore, monensin, was not an effective stimulus for beta-glucuronidase release or O2.- generation. The hyperpolarization response to neutrophils exposed to immune complexes and to concanavalin A was greatly diminished in both high [K+] and [choline] buffers. Thus, extracellular Na+ was required for an optimal membrane potential response to receptor-ligand interaction. Since O2.- generation and lysosomal enzyme release in response to the Ca2+ ionophore, A23187, were also reduced in the absence of extracellular Na+, it was concluded that extracellular Na+ was also required after induction of Ca2+ fluxes. Ouabain (1 mM) had no effect on O2.- generation, lysosomal enzyme release or the hyperpolarization response to immune complexes, indicating that the hyperpolarization observed on stimulation cannot be due to the action of the electrogenic pump, (Na+ + K+)-ATPase. The experiments indicate that extracellular Na+ is required (1) in the delta psi response triggered by receptor-ligand interaction, and (2) at a step(s) subsequent to Ca2+ fluxes and common to O2.- generation and lysosomal enzyme release.
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PMID:Stimulus-response coupling in the human neutrophil. Transmembrane potential and the role of extracellular Na+. 625 Jun 7

Insulin is apparently not required for VMH glucose oxidation in vitro. Ouabain, an inhibitor of the Na-K pump ATPase, does not prevent VMH glucose oxidation in vitro. These data suggest (a) the VMH does not exhibit a cotransport phenomenon of glucose with the Na-K pump mechanism, and (b) glucose oxidation in the VMH is not insulin dependent. Alloxan-diabetes was induced to increase tissue insulin sensitivity. A comparison of glucose oxidation rates in alloxan-diabetic VMH tissue and normal VMH tissue, supplemented only with saline, indicated a highly significant (p < 0.001) depression of glucose oxidation in the alloxan-treated tissue. Cell membranes in the VMH are perhaps altered by alloxan.
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PMID:Glucose oxidation in the ventromedial hypothalamus is not affected by insulin or ouabain but depressed by alloxan treatment. 625 92

The cardiac glycoside, ouabain, exerts its influence on spermatozoa by binding to and inhibiting Mg2+-activated Na+, K+-dependent ATPase that is located in the midpiece-tail membranes. Ouabain decreased intracellular potassium, increased intracellular sodium, and produced a biphasic and time-dependent effect on motility--stimulation at low concentrations and inhibition at high concentrations. The motility depression consisted of decreases in numbers of motile cells, percent progressive motility, beat frequency, and amplitude. Species differences and maturational age of the sperm cells were reflected in the degree of the ouabain effect and also the distribution of the ouabain-sensitive enzyme. The presence of this enzyme in spermatozoan membranes contributes significantly to regulation of sperm cell function through modulation of cationic fluxes which in "conventional" cell types influence their excitability.
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PMID:Effects of ouabain on spermatozoan function: a review. 626 5


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