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Rubidium uptake in single cells.

Rubidium uptake was measured in single erythroid and myeloid cells of rabbit by means of X-ray microanalysis. It was found in the nucleated bone marrow cells that after incubation in rubidium the sums of potassium and rubidium concentrations were similar to the original potassium concentrations, indicating that there was one-to-one replacement of potassium by rubidium. Although the nuclear potassium and rubidium concentrations were higher than those in the cytoplasm, the nuclear and cytoplasmic ratios of K/Rb were similar. This implies that the potassium in both compartments exchanged freely with rubidium. In the erythroid line of cells there was a continuous reduction of potassium transport activity during the maturation process as indicated by the decrease in rubidium uptake rates. The uptake was measured in seven groups of cell types that could be distinguished on the basis of morphology and chemical composition. The order of the groups from high to low rubidium uptake were: esosinophilic myelocyte greater than early erythroblast and thin-rimmed erythroblast greater than late erythroblast greater than early bone marrow red cell greater than late bone marrow red cell greater than peripheral blood red cell. Thus, there is a continuous decrease in rubidium transport as the erythroid cells mature.

Animals↗

The effects of long-term administration of rubidium or lithium on reactivity to stress and on dopamine output in the nucleus accumbens in rats.

Rubidium and lithium are alkali metals belonging to the same periodic series as sodium, potassium and cesium. In the present report the effects of lithium and rubidium on animal reactivity to stressful stimuli and on dopamine output in the nucleus accumbens were studied. A dose-response curve with rubidium, administered acutely before exposure to unavoidable stress, showed a maximal protective activity on escape deficit development at the dose of 0. 41 mEq/kg. Rubidium injected at doses of 0.008-0.08 mEq/kg 72 h before the unavoidable stress had the same efficacy as the acute 0. 41 mEq/kg dose. Tolerance to the effect of rubidium developed after 9 days of treatment and, on day 15, rats presented a spontaneous escape deficit. The acute effect of lithium, administered for 3.5 days at the dose of 0.8 mEq/kg, i.p. twice a day before the exposure to unavoidable stress, was analogous to that of rubidium, but after repeated treatment a spontaneous escape deficit developed. Rats showing an escape deficit secondary to chronic stress also presented decreased extraneuronal dopamine concentrations in the nucleus accumbens. Accordingly, microdialysis studies showed significantly lower extracellular dopamine levels in rats chronically treated with lithium or rubidium compared to control animals. Cocaine (5 mg/kg i. p.) administered acutely increased extracellular dopamine concentrations in control rats, as well as in rats chronically stressed or chronically treated with lithium or rubidium. However, the dopamine increase was significantly higher in controls compared to the other groups. In conclusion, long-term treatment with lithium or rubidium, or the exposure to chronic stress, produced a condition of behavioral hypo-reactivity accompanied by a decreased dopamine output in the nucleus accumbens.

Animals↗

Membrane potential and conductance during transport of sodium, potassium and rubidium in frog muscle.

1. Muscles with high intracellular sodium concentrations can extrude sodium into solutions which contain 10 m-equiv/l. of either potassium or rubidium. Potassium or rubidium replaces the extruded intracellular sodium. These cation movements take place equally well when the external anion is chloride or sulphate, though muscles deteriorate if left for long periods in sulphate solutions.2. Measurements of intracellular potentials during extrusion of sodium into solutions containing potassium show:(a) an internal potential more negative than the potassium equilibrium potential (E(K)); at 20 degrees C the difference is nearly 20 mV.(b) that a difference between the membrane potential and E(K) is dependent on temperature and is abolished by 10(-5)M ouabain.(c) an internal potential which becomes more negative in the presence of 0.1% cocaine, a concentration of cocaine which substantially increases the membrane resistance to potassium movement. In the absence of potassium or rubidium no such hyperpolarization occurs.3. When muscles extrude into solutions which contain rubidium they have internal potentials which are 10-20 mV more negative than when extruding sodium into corresponding solutions containing potassium.4. Measurements of electrical conductance in the potassium solution suggest that the electrochemical potential difference for potassium ions may be large enough to account for the measured inward potassium movements during sodium extrusion. The reliability of the measurements does not, however, exclude the possibility that some part of the inward potassium movement is chemically linked to outward movement.5. Measurements of membrane conductance in solutions containing rubidium, and of net movements of rubidium in the presence and absence of ouabain, lead to the conclusion that at least 90% of the inward rubidium movement during sodium extrusion must be chemically linked to the sodium movement.6. The hyperpolarization during extrusion of sodium could be explained on the basis of a fall of the potassium or rubidium concentration in a region of the extracellular space immediately external to the membrane. It is argued that certain characteristics of the hyperpolarization make it difficult to explain the hyperpolarization on this basis alone, though some part of it may be due to extracellular depletion of either potassium or rubidium.The main conclusion is that the sodium pump is capable of transferring electric charge across the membrane in which it is operating, but that, in a given time, the net charge transferred is less than the charge on the sodium ions that the pump has transported, by an amount that corresponds to the charge on the potassium or rubidium ions chemically transported by the pump.

Animals↗

Effect of low dietary rubidium on plasma biochemical parameters and mineral levels in rats.

The effects of low dietary rubidium on plasma biochemical parameters and mineral levels in tissues in rats were studied. Eighteen male Wistar rats, weighing about 40 g, were divided into two groups and fed the diets with or without supplemental rubidium (0.54 vs 8.12 mg/kg diet) for 11 wk. Compared to the rats fed the diet with supplemental rubidium, the animals fed the diet without rubidium supplementation had higher urea nitrogen in plasma; lower rubidium concentration in tissues; lower sodium in muscle; higher potassium in plasma, kidney and tibia, and lower potassium in testis; lower phosphorus in heart and spleen; lower calcium in spleen; higher magnesium in muscle and tibia; higher iron in muscle; lower zinc in plasma and testis; and lower copper in heart, liver, and spleen, and higher copper in kidney. These results suggest that rubidium concentration in tissues reflects rubidium intake, and that rubidium depletion affects mineral (sodium, potassium, phosphorus, calcium, magnesium, iron, zinc, and copper) status.

Animals↗

The kinetics of ouabain inhibition and the partition of rubidium influx in human red blood cells.

IN THE DEVELOPMENT OF OUABAIN INHIBITION OF RUBIDIUM INFLUX IN HUMAN RED BLOOD CELLS A TIME LAG CAN BE DETECTED WHICH IS A FUNCTION OF AT LEAST THREE VARIABLES: the concentrations of external sodium, rubidium, and ouabain. The inhibition is antagonized by rubidium and favored by sodium. Similar considerations could be applied to the binding of ouabain to membrane sites. The total influx of rubidium as a function of external rubidium concentration can be separated into two components: (a) a linear uptake not affected by external sodium or ouabain and not requiring an energy supply, and (b) a saturable component. The latter component, on the basis of the different effects of the aforementioned factors, can be divided into three fractions. The first is ouabain-sensitive, inhibited by external sodium at low rubidium, and requires an energy supply; this represents about 70-80% of the total uptake and is related to the active sodium extrusion mechanism. The second is ouabain-insensitive, activated by external sodium over the entire range of rubidium concentrations studied, and dependent on internal ATP; this represents about 15% of the total influx; it could be coupled to an active sodium extrusion or belong to a rubidium-potassium exchange. The third, which can be called residual influx, is ouabain-insensitive, unaffected by external sodium, and independent of internal ATP; this represents about 10-20% of the total influx.

Adenosine Triphosphate↗

Evidence for the ordered release of rubidium ions occluded within individual protomers of dog kidney Na+,K+-ATPase.

1. When magnesium and orthophosphate are added to Na+,K+-ATPase containing occluded rubidium ions, and suspended in a medium containing free rubidium ions, only 50% of the occluded rubidium is released rapidly. This is because the release of occluded rubidium is ordered, and the replacement (by rubidium ions from the medium) of the first occluded rubidium ions to leave slows the departure of the remaining occluded ions. 2. Since the Na+,K+-ATPase probably exists in the membrane as a structural dimer, the ordered release might represent either the ordered emptying of the two halves of the dimer, or the ordered release of the two rubidium ions thought to be contained in each promoter. 3. The present experiments were designed to decide between these possibilities by examining the behaviour of Na+,K+-ATPase in which about half of the protomers had been randomly inactivated by pre-treatment either with fluorescein isothiocyanate or with alpha-chymotrypsin. 4. The results show that the release of rubidium ions from each protomer is ordered.

Animals↗

Cell rubidium uptake: a method for studying functional heterogeneity in the nephron.

Rubidium uptake into individual tubule cells of rat renal cortex as measured by energy-dispersive X-ray microanalysis on freeze dried cryosections was used as an index of potassium transport. Over a 30 second period following intravenous infusion of rubidium (0.5 mmol/kg body wt) rubidium content increased in all cells. After 30 seconds, rubidium contents were (in mmol/kg dry wt): 225 +/- 8 in distal convoluted tubule cells, 156 +/- 7 in connecting tubule cells, 110 +/- 7 in principal cells, 86 +/- 4 in proximal tubule cells and 24 +/- 2 in intercalated cells (mean +/- SEM). When distal sodium and potassium transport were stimulated by hypertonic saline loading, rubidium uptake was selectively increased into distal convoluted tubule cells by 38%, into connecting tubule cells by 36%, and into principal cells by 52%. However, rubidium uptake into proximal tubule and into intercalated cells remained unchanged. The preferential uptake of rubidium into distal convoluted tubule cells, connecting tubule cells, and principal cells correlates well with the known transport functions of sodium and potassium, whereas intercalated cells are distinguished by low sodium and potassium transport activity.

Animals↗

[New vistas on rubidium].

Rubidium salts have been used in human therapy since the end of the last century. The fact that an actual use in psychiatry has been considered is mainly due to Meltzer and al's works in 1969. The pharmacological studies do not reveal any psychopharmacological "provile" presently known; they point out that Rubidium has stimulant properties, whick, in certain conditions, can increase activity, central excitability and sometimes aggressiveness, among the animals used for the experiments. The hypothesis of a contingent antidepressant action of Rubidium is essentially based on the existence of properties opposite to those of Lithium. This is especially true in the biochemical field: Rubidium may enhance the release of Norepinephrine whereas Lithium has an opposite effect. The toxicological studies show that, because of some properties common to Rubidium and Potassium, it is necessary to control Potassium intake and to avoid that Rubidium replace too high a percentage of this ion: the extended half-life (about forty days in man) makes necessary the working up of chronical studies to evaluate the toxicity which is linked to its long-term accumulation. For Rubidium blood concentrations superior to 1 mEq/1., the first clinical studies seem to point out that an antidepressant action would exist. Nevertheless a certain delay of action is necessary to the onset of a therapeutic effect; no noticeable adverse effect has been detected.

Animals↗

Relation between regional myocardial uptake of rubidium-82 and perfusion: absolute reduction of cation uptake in ischemia.

Experiments were undertaken using rubidium-82 and position tomography to examine the relation between myocardial perfusion and cation uptake during acute ischemia. Rubidium-82 was repeatedly eluted from a strontium-82-rubidium-82 generator. In six dogs emission tomograms were used to measure the delivered arterial and myocardial concentrations at rest and after coronary stenosis, stress and ischemia. There was a poor overall relation between regional myocardial uptake and flow measured by microspheres and a large individual variability. Extraction of rubidium-82 was inversely related to flow. Significant regional reduction of cation uptake was detected in the tomograms when regional flow decreased by more than 35 percent. This reduction was significantly greater when ischemia was present. A small but significantly greater when ischemia was present. A small but significant decrease (33.0 +/- 9.1 percent, mean +/- standard deviation) in the myocardial uptake of rubidium-82 was detected only when flow was increased by more than 120 percent in relation to a control area after administration of dypiridamole. The technique using rubidum-82 and tomography was applied in five volunteers and five patients with angina pectoris and coronary artery disease. Myocardial tomograms recorded at rest and after exercise in the volunteers showed homogeneous uptake of cation in reproducible and repeatable scans. In contrast, the patients with coronary artery disease showed an absolute mean decrease of 36 +/- 14 percent in regional myocardial uptake of rubidium-82 after exercise. These abnormalities persisted in serial tomograms for more than 20 minutes after the symptoms and electrocardiographic signs of ischemia.

Adult↗

A medium-throughput functional assay of KCNQ2 potassium channels using rubidium efflux and atomic absorption spectrometry.

Heterologous expression of KCNQ2 (Kv7.2) results in the formation of a slowly activating, noninactivating, voltage-gated potassium channel. Using a cell line that stably expresses KCNQ2, we developed a rubidium flux assay to measure the functional activity and pharmacological modulation of this ion channel. Rubidium flux was performed in a 96-well microtiter plate format; rubidium was quantified using an automated atomic absorption spectrometer to enable screening of 1000 data points/day. Cells accumulated rubidium at 37 degrees C in a monoexponential manner with t(1/2)=40min. Treating cells with elevated extracellular potassium caused membrane depolarization and stimulation of rubidium efflux through KCNQ2. The rate of rubidium efflux increased with increasing extracellular potassium: the t(1/2) at 50mM potassium was 5.1 min. Potassium-stimulated efflux was potentiated by the anticonvulsant drug retigabine (EC(50)=0.5 microM). Both potassium-induced and retigabine-facilitated efflux were blocked by TEA (IC(50)s=0.4 and 0.3mM, respectively) and the neurotransmitter release enhancers and putative cognition enhancers linopirdine (IC(50)s=2.3 and 7.1 microM, respectively) and XE991 (IC(50)s=0.3 and 0.9 microM, respectively). Screening a collection of ion channel modulators revealed additional inhibitors including clofilium (IC(50) = 27 microM). These studies extend the pharmacological profile of KCNQ2 and demonstrate the feasibility of using this assay system to rapidly screen for compounds that modulate the function of KCNQ2.

Anthracenes↗

Effects of external cesium and rubidium on outward potassium currents in squid axons.

We have studied the effects of external cesium and rubidium on potassium conductance of voltage clamped squid axons over a broad range of concentrations of these ions relative to the external potassium concentration. Our primary novel finding concerning cesium is that relatively large concentrations of this ion are able to block a small, but statistically significant fraction of outward potassium current for potentials less than approximately 50 mV positive to reversal potential. This effect is relieved at more positive potentials. We have also found that external rubidium blocks outward current with a qualitatively similar voltage dependence. This effect is more readily apparent than the cesium blockade, occurring even for concentrations less than that of external potassium. Rubidium also has a blocking effect on inward current, which is relieved for potentials more than 20-40 mV negative to reversal, thereby allowing both potassium and rubidium ions to cross the membrane. We have described these results with a single-file diffusion model of ion permeation through potassium channels. The model analysis suggests that both rubidium and cesium ions exert their blocking effects at the innermost site of a two-site channel, and that rubidium competes with potassium ions for entry into the channel more effectively than does cesium under comparable conditions.

Animals↗

Effects of rubidium on behavioral responses to methamphetamine and tetrabenazine.

Different groups of mice were injected subcutaneously every other day with rubidium chloride at three doses (0.41(50), 1.23(150) and 3.69(450) meq/kg (mg/kg)) or with saline as a control for a period of 2-3 weeks. Rubidium administered acutely did not affect spontaneous locomotor activities, while it tended to increase the activities when administered repeatedly though the increase was not statistically significant. The methamphetamine-induced hyperlocomotor activities were potentiated in the rubidium groups as compared with those in the saline group, this effect of ribidium being increased with prolongation of repeated administrations. Monotonic decreases in ambulation after tetrabenazine were not significantly affected in the rubidium-treated animals though the decreases were sometimes preceded by slight increases and recovery from the decrement tended to be more rapid. After tetrabenazine in the rubidium-treated groups, incidences of catalepsy were increased and jumping behavior and Straub tail responses occurred in a few cases. The results suggest that rubidium potentiates the excitatory action of methamphetamine on spontaneous locomotor activities, as contrasted with inhibitory influence of lithium.

Animals↗

[Changes in the plasma and erythrocyte concentrations of rubidium in patients with renal failure].

Rubidium concentrations were measured by flame emission spectrophotometry in whole blood, plasma and red cells from male and female controls and from dialyzed and non-dialyzed patients of both sexes with chronic renal failure. Rubidium concentrations (mumol/l) in male and female controls respectively were: 2.29 +/- 0.29 and 1.96 +/- 0.46 in plasma: 36..79 +/- 5.90 and 30.19 +/- 6.11 in whole blood; 74.57 +/- 10.37 and 72.22 +/- 12.76 in erythrocytes. The red cell rubidium/plasma rubidium ratios were 32.6 in males and 38.3 in females. Compared with controls, dialyzed male and female patients showed, before dialysis, a decrease in rubidium concentrations of respectively -30% and -17% in plasma, -64% and -61% in whole blood, -40% and -33% in erythrocytes. A further decrease of 25% in rubidium plasma concentrations was observed after dialysis. Non dialyzed patients had an increase in plasma concentrations (+14% in males, +23% in females) and a decrease in erythrocyte concentrations (-16% in males, -20% in females) as compared with controls. Our data show that plasma and red cell rubidium concentrations are fairly constant and probably regulated in healthy subjects but vary considerably in patients with renal failure.

Adult↗

Rubidium reduces potassium permeability and fluid secretion in Malpighian tubules of Locusta migratoria, L.

The basal membrane potential (V(b)) of Locusta Malpighian tubule cells in control saline results from its relatively high permeability to potassium. In the presence of 1 mM barium added to the control saline V(b) hyperpolarized from a mean resting potential of -72.1 mV to -90.1 mV. On substituting rubidium for potassium in the control saline, V(b) also hyperpolarized to a value of -91.4 mV. Rubidium was also similarly effective in hyperpolarizing the basal membrane even in the presence of control concentrations of potassium in the bathing medium. Substitution of rubidium for potassium also effected a approximately 50% reduction in the rate of fluid secretion. The action of inhibitors on V(b) in the presence of rubidium showed that V(b) under these conditions probably originated from the bafilomycin-sensitive electrogenic potential generated across the apical membrane by a V-type ATPase. The responses of V(b) to potassium, barium and rubidium and their inhibition of fluid secretion suggest the presence of a substantial rubidium-blockable potassium conductance located on the basal membrane of Locusta Malpighian tubule cells.

Journal Article↗

Crystal structure and ionic conductivity of three polymorphic phases of rubidium trifluoromethyl sulfonate, RbSO3CF3.

The crystal structures of three polymorphic phases of rubidium trifluoromethyl sulfonate (RbSO3CF3, rubidium 'triflate') were solved from X-ray powder diffraction data. At room temperature, rubidium triflate crystallizes in the monoclinic space group Cm with lattice parameters of a = 19.9611(5) A, b = 23.4913(7) A, c = 5.1514(2) A, beta = 102.758(2) degrees; Z = 16. At T = 321 K, a first-order phase transition occurs toward a monoclinic phase in space group P2(1) with lattice parameters at T = 344 K of a = 10.3434(5) A, b = 5.8283(3) A, c = 5.1982(3) A, beta = 104.278(6) degrees; Z = 2). At T = 461 K, another phase transition, this time of second order, occurs toward an orthorhombic phase in space group Cmcm with lattice parameters at T = 510 K of a = 5.3069(2) A, b = 20.2423(10) A, c = 5.9479(2) A; Z = 4. As a common feature within all three crystal structures of rubidium triflate, the triflate anions are arranged in double layers with the lipophilic CF3 groups facing each other. The rubidium ions are located between the SO3 groups. The general packing is similar to the packing in cesium triflate. Rubidium triflate can be classified as a solid electrolyte with a specific ionic conductivity of sigma = 9.89 x 10(-9) S/cm at T = 384 K and sigma = 3.84 x 10(-6) S/cm at T = 481 K.

Journal Article↗

Renal tolerance of rubidium chloride: short-term clinical evaluation.

The rubidium and lithium ions are known to have opposite effects on a wide range of biochemical and behavioral parameters in experimental animals. Based on the proven effectiveness of lithium as an antimanic agent, several trials have been conducted with rubidium in the acute treatment of the depressive phase of bipolar illness. The results to date are promising. However, the 30- to 60-day biologic half-life of rubidium has mandated careful studies of potential toxicity before engaging in long-term administration of this ion to depressive subjects. One area of potential concern is the possibility of renal toxicity, which could be expressed as unexpectedly increased retention of rubidium. The data in this paper show that after 15 days of rubidium administration, there are no changes beyond the normal range in a variety of kidney function tests, including in four enzymes which are specific markers of tubule cell function.

Aged↗

Comparison of thallium-201 SPECT redistribution patterns and rubidium-82 PET rest-stress myocardial blood flow imaging.

To compare regional thallium-201 SPECT redistribution patterns with rubidium-82 PET, we studied 81 patients with both imaging modalities. Sixty patients had significant coronary artery disease. All patients underwent PET imaging after dipyridamole infusion, while SPECT imaging was performed after exercise stress (38 patients) and dipyridamole (43 patients). Sixty-eight percent of patients with prior infarct had fixed defects on SPECT, compared to 39% with PET. Sixty-one percent of patients with prior infarct had PET perfusion defects which exhibited 'reflow' or normal rubidium-82 tracer uptake (p < 0.05 vs. SPECT). Similar results were seen in patients without prior infarct (26% fixed defects on SPECT vs. 12% for PET, p < 0.05). Regional analysis showed that 57% of fixed SPECT defects corresponded to PET defects with reflow or normal rubidium-82 uptake, while 78% of 'fixed' PET defects corresponded to fixed SPECT defects. PET reflow and normal rubidium-82 uptake in sites of fixed thallium-201 SPECT perfusion defects suggest that imaging modalities employing separate tracer injections at rest and after stress, such as rubidium-82 PET, may be more specific in the assessment of myocardial viability, especially in patients with prior myocardial infarction.

Aged↗

Optimisation of parameters for determination of rubidium in spent CAPD fluids by flame and electrothermal atomic absorption spectrometry.

An analytical procedure is reported for the determination of rubidium in spent continuous ambulatory peritoneal dialysis (CAPD) fluids by flame and electrothermal atomic absorption spectrometry (FAAS, ETAAS). Samples of spent CAPD fluids were collected as 5 ml aliquots in polyethylene tubes and stored in a freezer at -20 degrees C. Before analysis, samples were equilibrated to room temperature and analysed within 8 h. A total of 2 mg ml(-1) of caesium was added to each sample and standard solution to overcome interferences from ionisation. An air-acetylene flame was applied in FAAS determinations. Analysis was performed against aqueous standards. The calibration graph was linear from 30.0 up to 5000 microg l(-1) Rb, while the limit of detection (3 s) was found to be 20.0 microg l(-1) rubidium. Good repeatability of measurement (RSD 1%) was obtained. Parameters were also optimised for determination of rubidium in spent CAPD fluids by ETAAS. Ten-fold diluted samples (3.5% nitric acid) were analysed applying standard addition calibration. The calibration graph was linear from 2.0 up to 30.0 microg l(-1) rubidium, while the limit of detection (3 s) was found to be 1.0 microg l(-1) rubidium (sample volume 10 microl). Good repeatability of measurement (RSD 5%) was obtained. The results of direct determination by FAAS and ETAAS were compared to those obtained after acid digestion of samples in Parr bombs. The accuracy of the procedure for direct determination was checked by spiking samples. In 73% of samples analysed, the differences between the results obtained by the two techniques, either for direct determinations of samples or for samples digested in a Parr bomb did not exceed +/-10%.

Dialysis Solutions↗