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1.
Irene Szumiel Danuta Włodek György Lustyik 《Radiation and environmental biophysics》1984,23(4):255-267
Summary We examined the response of L5178Y-S (radiosensitive, LY-S) and L517SY-R (radioresistant, LY-R) lymphoblasts to X-irradiation with concomittant treatment with divalent cation ionophore, A23187 (3 h or 5 h, 5 µg/ml). Cells treated with A23187 alone progressed through the cell cycle more slowly than the untreated cells and their cloning efficiency was reduced. In both cell strains the ionophore prolonged duration of the postirradiation mitotic delay. Radiation-induced inhibition of DNA synthesis was reversed by A23187 in LY-S but not in LY-R cells.Cells subjected to the ionophore treatment survived X-irradiation in almost the same way as untreated cells, as if the effect of A23187 treatment were reversed by irradiation. There was also a reversion in the ion content: A23187 caused a marked increase in Na+ content and a decrease in K+ content, irradiation itself did not change the ion content, whereas in the A23187-treated cells it restored almost the same pattern as that found in the control cells. We found less Mg2+ ions in LY-S cells after treatment with A23187 and A23187 + X than in LY-R cells, in relation to untreated (control) cells. These observations point to the possible importance of ion transport for recovery from radiation damage. 相似文献
2.
Ehrlich ascites tumor cells lose KCl and shrink after swelling in hypotonic media and in response to the addition of 2-deoxyglucose, propranolol, or the Ca2+ ionophore, A23187, plus Ca2+ in isotonic media. All of these treatments activate cell shrinkage via a pathway with the following characteristics: (1) the KCl loss responsible for cell shrinkage does not alter the membrane potential; (2) NO3? does not substitute for Cl?; (3) the net KCl movements are not inhibited by quinine or DIDS; and (4) early in this study furosemide was effective in inhibiting cell shrinkage but this sensitivity was subsequently lost. This evidence suggests that the KCl loss in these cells occurs via a cotransport mechanism. In addition, hypotonic media and the other agents used here stimulate a Cl? -Cl? exchange, a net loss of K+ and a net gain of Na+ which are not responsible for cell shrinkage. The Ehrlich cell also appears to have a Ca2+-activated, quinine-sensitive K+ conductive pathway but this pathway is not part of the mechanism by which these cells regulate their volume following swelling or shrink in isotonic media in response to 2-deoxyglucose or propranolol. Shrinkage by the loss of K+ through the Ca2+ stimulated pathway appears to be limited by Cl? conductive movements; for when NO3?, an anion demonstrated here to have a higher conductive movement than Cl?, is substituted for Cl?, the cells will shrink when the Ca2+-stimulated K+ pathway is activated. 相似文献
3.
William Lake Howard Rasmussen David B. P. Goodman 《The Journal of membrane biology》1977,32(1):93-113
Summary Addition of 0.1–0.3 m A23187, a divalent cation ionophore, to human erythrocytes suspended in a 1.0mm
45Ca2+-containing buffer results in a small ( two fold) increase in [Ca2+]
i
, a significant decrease in osmotic fragility, and a decrease in intracellular K+ (100 mmoles/liter of cells to 70 mmoles/liter cells) without significant alteration of intracellular [Na+]. This decrease in [K+]
i
is associated with a significant decrease in packed cell volume and correlates directly with the observed alteration is osmotic fragility. Increasing extracellular K+ to 125mm prevents the A23187-induced changes in osmotic fragility, K+ content and cell volume, but does not prevent the ionophore-induced uptake of45Ca2+. Addition of 0.1–0.3 m A23187 to toad erythrocytes leads to an increase in45Ca2+ uptake comparable to that observed in human erythrocytes, but does not alter osmotic fragility, cell volume or K+ content. Higher concentrations of ionophore (3.0–10.0 m) cause a 30- to 50-fold increase in45Ca2+ uptake and concomitant change in K+ content, cell volume and osmotic fragility. These changes in cell properties can be prevented by increasing extracellular [K+] to 90mm. The difference in sensitivity of the two cell types to A23187 is attributed to the presence of additional intracellular calcium pools within toad erythrocytes that prevent an increase in cytoplasmic Ca2+ until Ca2+ uptake is increased substantially at the higher concentrations of A23187. 相似文献
4.
The possible presence and properties of the Ca2+-dependent K+ channel have been investigated in the Ehrlich ascites tumor cell. The treatment with ionophore A23187+Ca2+, propranolol or the electron donor system ascorbate-phenazine methosulphate, all of which activate that transport system in the human erythrocyte, produces in the Ehrlich cell a net loss of K+ (balanced by the uptake of Na+) and a stimulation of both the influx and the efflux of 86Rb. These effects were antagonized by quinine, a known inhibitor of the Ca2+-dependent K+ channel in other cell systems, and by the addition of EGTA to the incubation medium. Ouabain did not have an inhibitory effect. These results suggests that the Ehrlich cell possesses a Ca2+-dependent K+ channel whose characteristics are similar to those described in other cell systems. 相似文献
5.
《生物化学与生物物理学报:生物膜》1987,899(2):313-316
The increase in Ca2+ permeability by addition of ionophore A23187 in the presence of external Ca2+ did not alter the bumetanide-sensitive Na+/K+ effluxes in human red blood cells. An inhibition of this pathway by cellular Ca2+ could be observed only under conditions in which the cellular ATP content was drastically depleted. 相似文献
6.
A. Cittadini D. Bossi A.M. Dani G. Calviello F. Wolf T. Terranova 《生物化学与生物物理学报:生物膜》1981,645(2):177-182
The Ca2+ ionophore A23187 increases intracellular calcium content in normal thymic cells, while it is without effect on the corresponding neoplastic cell (Ascites thymoma) and on Ehrlich ascites tumour cells. The A23187-induced total cell calcium increase in normal thymocytes takes place both in control and energy-depleted cells, while it is lacking in neoplastic cells. In addition the ionophore stimulates aerobic glycolysis of normal thymocytes, whereas it is ineffective on neoplastic cells. The study of intracellular calcium exchange properties reveals that in normal cells the ionophore A23187 provokes a 60% increase of the exchangeable pool together with a more significant, 4-fold enlargement of the unexchangeable pool. These effects are lacking in cancer cells. The data give rise to interesting considerations concerning the regulation and compartmentalization of calcium in neoplastic cells. The results will be also discussed in relation to the models that predict altered cell calcium metabolism as a cause of cancer cell high aerobic glycolysis and uncontrolled growth. 相似文献
7.
Red cells of adult sheep, like those of other ruminants, lack the calcium-activated potassium channel which is present in the membrane of human red cells. Since the activities of other transport systems in the sheep red cell are known to decrease during maturation of the cell or during development of the animal it was investigated whether the K+ channel is present in red cells from younger animals or in reticulocytes. Using the divalent cation ionophore A23187 to increase the intracellular Ca of intact cells, it was found that the K+-selective channel is present in foetal red cells from the foetus or newborn animal but not in reticulocytes. The presence of the channel showed no dependence on the K+ genotype of the sheep and was not associated with either “high K+”-or “low K+”-type Na+ pump. No Ca2+-dependent change in K+ permeability was found in red cells from either newborn or adult donkeys suggesting that its presence in the red cells of the foetus may not be general. The role of the K+ channel in the mammalian red cell and the relationship between the K+ channel and the Na+ pump are discussed. 相似文献
8.
The tissue/medium distribution of the nonmetabolized glucose analog [14C]-3-0-methyl-D-glucose was measured in pigeon erythrocytes and related to changes in 45Ca uptake and efflux, total calcium content and ATP levels. Sugar transport was not affected by changes in external Ca2+. However, both sugar and 45Ca influx were increased by the Ca-ionophore A23187. In the absence of external Ca2+, the ionophore caused a delayed increase in sugar transport and net loss of calcium, probably through releasing Ca2+ from internal storage sites into the cytoplasm. Increasing internal Na+ through Na+ pump inhibition or using the sodium ionophore monensin did not alter influx of sugar or 45Ca, indicating Na+-Ca2+ exchange was absent in these cells. The results are consistent with A23187 causing increased Ca2+ influx or release from mitochondrial storage and the resulting rise in cytoplasmic Ca2+ stimulating hexose transport. Experiments with low Mg++ and high K+ media and measurements of ATP levels exclude alternative explanations for the action of A23187. We conclude that sugar transport regulation in avian erythrocytes is Ca2+-dependent and resembles that in muscle in its basic mechanism. It differs in the response to some modulating agents, largely because of a different pattern of Ca2+ fluxes in these cells. 相似文献
9.
The ionic requirements for K+-evoked efflux of endogenous taurine from primary cerebellar astrocyte cultures were studied. The Ca2+ ionophore A23187 evoked taurine efflux in a dose-dependent fashion with a time-course identical to that of K+-induced efflux. The Ca2+-channel antagonist nifedipine had no effect upon efflux induced by 10 or 50 mM K+. In addition, verapamil did not antagonize 50 mM K+-evoked efflux except at high, non-pharmacological concentrations (>100 M), and preincubation with 2 M -conotoxin had no effect on 50 mM K+-evoked efflux. Similarly, preincubation with 1 mM ouabain had no effect on the amount of taurine released by K+ stimulation, but did accelerate the onset of efflux by 2–4 min. Although 2 M tetrodotoxin had no effect on K+-evoked release, replacing Na+ with choline abolished the taurine efflux seen in response to K+ stimulation. Together, these findings suggest that neuronal N- and L-type Ca2+- and voltage-dependent Na+-channels are not involved in the influx of Ca2+ which appears to be necessary for K+-evoked taurine efflux, and that in addition to Ca2+, extracellular Na+ is also required. 相似文献
10.
Measurements of 86Rb efflux across the apical and basal-lateral aspects of intact monolayers of ‘high-resistance’ MDCK cells mounted in Ussing chambers have been made. A transient increase in 86Rb efflux across both epithelial borders upon stimulation with adrenalin or ionophore A23187 is observed. The increased 86Rb across the basal cell aspects is of greatest quantitative importance. Measurements of total cellular K+ contents by flame photometry of tissue extracts indicate a net loss of K+ following adrenalin addition. The effects of adrenalin and ionophore A23187 upon 86Rb efflux are abolished in ‘Ca2+-free’ media. The properties of the Ca2+ -dependent increase in 86Rb efflux show similarities to Ca2+-activated K+ conductances in other tissues, notably human red cells, including inhibition by quinine (1 mM), tetraethylammonium (25 mM) and insensitivity to bee venom toxin (apamin) (25 nM). Adrenalin is only effective when applied to the basal bathing solution suggesting that the receptors mediating adrenalin action are located upon the basal-lateral membranes. Half maximal stimulation of 86Rb efflux by adrenalin is observed at 9.1·10?7 M. The action of various adrenergic receptor agonists and antagonists are consistent with adrenalin action being mediated by an α-adrenergic receptor. 相似文献
11.
Summary Microscopic observations of isotonic suspensions of human red blood cells demonstrate that cell shape is unaltered when the transmembrane electrical potential, orE
m
, is set in the range –85 to +10 mV with valinomycin at varied external K+, or K
o
.E
m
was measured with the fluorescent potentiometric indicator, diS-C3(5), as calibrated by a pH method. Repeating Glaser's experiments in which echinocytosis was attributed to hyperpolarization, we found that at low ionic strength the pH-dependent effects of amphotericin B appear to be unrelated toE
m
. The effects of increased intracellular Ca2+, or Ca
o
, on echinocytosis and onE
m
are separable. With Ca ionophore A23187 half-maximal echinocytosis occurs at greater Ca
o
than that which induces the half-maximal hyperpolarization associated with Ca-induced K+ conductance (Gardos effect). Thus, cells hyperpolarized by increased Ca
o
remain discoidal when Ca is below the threshold for echinocytosis. With A23187 and higher Ca
o
, extensive echinocytosis occurs in cells which are either hyperpolarized or at their resting potential. The Ca-activation curve for echinocytosis is left-shifted by low K
o
, a new observation consistent with increased DIDS-sensitive uptake of45Ca by hyperpolarized cells. These results support the following conclusions: (1) the shape and membrane potential of human red blood cells are independent under the conditions studied; (2) in cells treated with A23187, the Gardos effect facilitates echinocytosis by increasing Ca. 相似文献
12.
Charybdotoxin blocks with high affinity the Ca-activated K+ channel of Hb A and Hb S red cells: Individual differences in the number of channels 总被引:4,自引:0,他引:4
Daniel Wolff Ximena Cecchi Anda Spalvins Mitzy Canessa 《The Journal of membrane biology》1988,106(3):243-252
Summary We have investigated the effect of a purified preparation of Charybdotoxin (CTX) on the Ca-activated K+ (Ca–K) channel of human red cells (RBC). Cytosolic Ca2+ was increased either by ATP depletion or by the Ca ionophore A23187 and incubation in Na+ media containing CaCl2. The Ca–K efflux activated by metabolic depletion was partially (77%) inhibited from 15.8±2.4 mmol/liter cell · hr, to 3.7±1.0 mmol/liter cell · hr by 6nm CTX (n=3). The kinetic of Ca–K efflux was studied by increasing cell ionized Ca2+ using A23187 (60 mol/liter cell), and buffering with EGTA or citrate; initial rates of net K+ efflux (90 mmol/liter cell K+) into Na+ medium containing glucose, ouabain, bumetanide at pH 7.4 were measured. Ca–K efflux increased in a sigmoidal fashion (n of Hill 1.8) when Ca2+ was raised, with aK
m of 0.37 m and saturating between 2 and 10 m Ca2+. Ca–K efflux was partially blocked (71±7.8%, mean ±sd,n=17) by CTX with high affinity (IC500.8nm), a finding suggesting that is a high affinity ligand of Ca–K channels. CTX also blocked 72% of the Ca-activated K+ efflux into 75mm K+ medium, which counteracted membrane hyperpolarization, cell acidification and cell shrinkage produced by opening of the K+ channel in Na+ media. CTX did not block Valinomycin-activated K+ efflux into Na+ or K+ medium and therefore it does not inhibit K+ movement coupled to anion conductive permeability.TheV
max, but not theK
m–Ca of Ca–K efflux showed large individual differences varying between 4.8 and 15.8 mmol/liter cell · min (FU). In red cells with Hb A,V
max was 9.36±3.0 FU (mean ±sd,n=17). TheV
max of the CTX-sensitive, Ca–K efflux was 6.27±2.5 FU (range 3.4 to 16.4 FU) in Hb A red cells and it was not significantly different in Hb S (6.75±3.2 FU,n=8). Since there is larger fraction of reticulocytes in Hb S red cells, this finding indicates that cell age might not be an important determinant of theV
max of Ca–K+ efflux.Estimation of the number of CTX-sensitive Ca-activated K+ channels per cell indicate that there are 1 to 3 channels/per cell either in Hb A or Hb S red cells. The CTX-insensitive K+ efflux (2.7±0.9 FU) may reflect the activity of a different channel, nonspecific changes in permeability or coupling to an anion conductive pathway. 相似文献
13.
Previous results with potato tuber discs showed that a treatment with abscisic acid stimulated K+ uptake. In this investigation, we determine the relationship between increased K' uptake and H+extrusion, and Ca2+ fluxes by treating tissues with specific Ca2+ channel blocker (La3+), calmodulin (CaM) inhibitors (chlorpromazine and W7), and with Ca2+ ionophore (A23187). K+ uptake increased with increasing external pH whether tissues were treated with ABA or not. Treatment of tissues with La3+ inhibited K+ uptake, whereas CaM inhibitors have no effect. By contrast ABA and A23187 produced a synergistic effect, suggesting that
ABA may act in part, on K+ uptake, like a Ca2+ agonist, in accord with Huddart's hypothesis.
This revised version was published online in July 2006 with corrections to the Cover Date. 相似文献
14.
Low concentrations of chelating agents such as EDTA prevent the air oxidation of vanadyl (VO2+, +4 oxidation state) to vanadate (VO3?, +5 oxidation state). Under these conditions, the ionophore A23187 mediates the rapid entry of vanadyl into human erythrocytes. In the presence of A23187, vanadyl at concentrations in excess of EDTA gives rise to a dramatic increase in K+ permeability, which is very similar to the Gardos Ca2+-induced K+ permeability increase with respect to ion selectivity, response to inhibitors, effects of pH, and stimulation by external K+. In ultrapure media with very low Ca2+, however, vanadyl has no effect on K+ permeability. These experiments suggest that Ca2+ is displaced from EDTA by vanadyl and then enters the cell via A23187 where it triggers the increase in K+ permeability. This hypothesis is confirmed by experiments demonstrating that vanadyl does displace Ca2+ from EDTA. Vanadate, an inhibitor of Ca2+-ATPase, causes a selective increase in K+ permeability in metabolically depleted cells, but the increase is abolished by low concentrations of EDTA, indicating that this effect is also due to entry of extracellular Ca2+. Earlier observations of effects of vanadyl and vanadate on erythrocyte K+ permeability can thus be explained on the basis of inhibition of the Ca2+ pump by vanadium, leading to an increase in intracellular Ca2+ concentration. 相似文献
15.
The efflux of K+ and Na+ from sea urchin eggs during Ca2+ ionophore A23187-induced parthenogenesis was studied in a K+ and Na+-free artificial seawater using extracellular ion-specific electrodes. We have probed this model system with monovalent cation-specific ionophores to determine if they affect K+ efflux in the unfertilized egg and whether any changes in ionophore sensitivity are observed during egg activation. In 500 mM choline chloride, 10 mM CaCl2, 50 mM MgCl2, 10 mM Tris-Cl pH 8.0, A23187 induced a rapid efflux of K+ and Na+ from the eggs after a short lag time (10–15 seconds). After the burst, the rate of K+ efflux remained higher than the pre-activation rate, but was lower than during the burst phase, while the rate of Na+ efflux became nearly zero. Monovalent cation-specific ionophores (valinomycin, gramicidin and nigericin) had no effect on K+ efflux from the unfertilized eggs in our model system. However, once the egg was activated by A23187, each of the above ionophores caused a prolongation of the burst phase for many minutes. These results show that the unfertilized egg plasma membrane (using our artificial conditions) is not susceptible to the monovalent cation-specific antibiotics and suggest that either the inserted cortical granule membrane or the developing fertilization envelope interacts with these ionophores to cause the change in rate-limiting step for K+ efflux observed egg activation. 相似文献
16.
Eewa Nånberg Eamonn Connolly Jan Nedergaard 《Biochimica et Biophysica Acta (BBA)/Molecular Cell Research》1985,844(1):42-49
We have previously demonstrated mobilization of Ca2+ in the efflux of Rb+ (K+) from isolated hamster brown adipocytes as a consequence of norepinephrine stimulation. We have now investigated the adrenoceptor subtype specificity of these responses and found them both to be of theα1-subtype. Futher, we have found that the Rb+ (K+) effux was dependent upon a primary Ca2+mobilization event in response to the α1-adrenergic stimulation, since the Rb+ efflux could also be demonstrated by the addition ionophore A23187 to the cells. The norepinephrine- and A23187-stimulated Rb+ effluxes were both inhibited by the Ca2+-dependent K+ -channel blocker apamin. Apamin also significantly attenuated Ca2+ mobilization in cells in response to a submaximal concentration of norepinephrine. We conclude that α1-adrenergic stimulation of brown fat cells leads to a mobilization of intracellular Ca2+ which, in itself or via other mechanisms, leads to an increase in cytosolic Ca2+ concentration which, in turn, activates a Ca2+ -dependent K+ channel leading to a K+ release from these cells. A possible role for this channel to sustain and augment the response toα1-adrenergic stimulation is discussed. 相似文献
17.
Ionophore A23187-mediated net influx of Ca2+ in ATP-depleted human red cells was studied as a function of the pH and the proton concentration gradient across the membranes. Utilizing the Ca2+-induced increase in K+ conductance of the cell membranes, various CCCP-mediated proton gradients were raised across the membranes of cells suspended in unbuffered salt solutions with different K+ concentrations. In ionophore-mediated equilibrium the concentration ratios of ionized Ca between ATP-depleted, DIDS-treated cells and their suspension medium were equal to the concentration ratios of protons raised to the second power. With no proton concentration gradient across the membranes the net influxes of Ca2+ as a function of pH resembled a titration curve of a weak acid, with half maximal net influx at pH 7.3, at 100 μM extracellular Ca2+. With cellular pH fixed at various values, the net influx of Ca2+ was determined as a function of the proton concentration gradient. A linear relationship between the logarithm of net influx and the difference between extracellular and cellular pH was found at all cellular pH values tested, but the proton concentration gradient acceleration was a function of the cellular pH. Accelerations between 10- and 40- times per unit ΔpH were found and net effluxes were correspondingly decreased. The results are discussed in relation to present models of the mechanism of ionophore A23187-mediated Ca2+ transport. The importance of the proton concentration gradient dependency is discussed in relation to the induced oscillations in K+-conductance of human red cell membranes previously reported (Vestergaard-Bogind and Bennekou (1982) Biochim. Biophys. Acta 688, 37ndash;44). 相似文献
18.
John A. Hickman Owen C. Blair Anita L. Stepanowski Alan C. Sartorelli 《生物化学与生物物理学报:生物膜》1984,778(3):457-462
Ionophore-induced changes in the cell-associated fluorescence of samples of approx. 50 000 individual murine L1210 leukemia cells which had been incubated with the voltage-sensitive dye 3,3′-dihexyloctacarbocyanine iodide (DiOC6(3)) were monitored by flow cytometry. The K+ ionophore valinomycin (1 μM) produced homogeneous changes in the fluorescence of the entire population, the magnitude of which was dependent upon the concentration of extracellular K+. These changes allowed the estimation of the potassium equilibrium potential of the cells, by the null-point method, to be – 11.9 mV. The Ca2+ ionophore A23187 (500 nM) produced heterogeneous changes in fluorescence, with populations of both hyperpolarised and depolarised cells. In addition, the depolarised population underwent an apparent size change, with a reduction in cell volume. This heterogeneity of response resulted in a minimal change in the median fluorescence value for the whole population, which suggests that it would not have been detectable by methods dependent upon net population-averaged changes in fluorescence. Removal of extracellular Na+ or preincubation of cells with amiloride (500 μM) effectively eliminated the depolarised population. Removal of extracellular K+ increased the hyperpolarised population. These findings provide evidence for the presence of Ca2+-induced Na+ exchange and Ca2+-induced K+ efflux mechanisms in these cells which may be expressed simultaneously in the cell population. 相似文献
19.
Patricia M. Sokolove 《BBA》1979,545(1):155-164
The conditions under which ionophore A23187 can be used as a probe of Mg2+ involvement in the reactions of intact (Type A) spinach chloroplasts have been investigated by monitoring ionophore-induced reversal of slow fluorescence quenching. The following observations were made: (1) A23187-dependent reversal of quenching is a strong function of pH. This is consistent with competition between protons and divalent cations for the carboxylic acid moiety of the ionophore. (2) In the presence of exogenous Mg2+, quenching reversal by A23187 is significantly slowed. It is suggested that formation of the dimeric A23187 · Mg2+ complex delays action of the ionophore at the thylakoid membrane by slowing equilibration of the ionophore among chloroplast membrane phases. (3) In the absence of Mg2+, significant interaction of A23187 with certain monovalent cations — Li+ and Na+, but not K+ — is observed. Evaluations of the interaction of ionophore A23187 with specific biological systems and inferences of divalent cation involvement, or lack thereof, must take these limitations into account. 相似文献
20.
Intracellular calcium content of human erythrocytes: Relation to sodium transport systems 总被引:2,自引:0,他引:2
Summary To study the possible role of intracellular Ca (Ca
i
) in controlling the activities of the Na+–K+ pump, the Na+–K+ cotransport and the Na+/Li+ exchange system of human erythrocytes, a method was developed to measure the amount of Ca embodied within the red cell. For complete removal of Ca associated with the outer aspect of the membrane, it proved to be essential to wash the cells in buffers containing less than 20nm Ca. Ca was extracted by HClO4 in Teflon® vessels boiled in acid to avoid Ca contaminations and quantitated by flameless atomic absorption. Ca
i
of fresh human erythrocytes of apparently healthy donors ranged between 0.9 and 2.8 mol/liter cells. The mean value found in females was significantly higher than in males. The interindividual different Ca contents remained constant over periods of more than one year. Sixty to 90% of Ca
i
could be removed by incubation of the cells with A23187 and EGTA. The activities of the Na+–K+ pump, of Na+–K+ cotransport and Na+/Li+ exchange and the mean cellular hemoglobin content fell with rising Ca
i
; the red cell Na+ and K+ contents rose with Ca
i
. Ca depletion by A23187 plus EGTA as well as chelation of intracellular Ca2+ by quin-2 did not significantly enhance the transport rates. It is concluded that the large scatter of the values of Ca
i
of normal human erythrocytes reported in the literature mainly results from a widely differing removal of Ca associated with the outer aspect of the membrane. 相似文献