[Periodic variations of the chloride electrochemical potential difference during spontaneous oscillations of the membrane potential in Nitella].
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Cell Membrane↗
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Contribution of the K(Ca) channel to membrane potential and O2 sensitivity is decreased in an ovine PPHN model.
Ca2+-sensitive K+ (K(Ca)) channels play an important role in mediating perinatal pulmonary vasodilation. We hypothesized that lung K(Ca) channel function may be decreased in persistent pulmonary hypertension of the newborn (PPHN). To test this hypothesis, pulmonary artery smooth muscle cells (PASMC) were isolated from fetal lambs with severe pulmonary hypertension induced by ligation of the ductus arteriosus in fetal lambs at 125-128 days gestation. Fetal lambs were killed after pulmonary hypertension had been maintained for at least 7 days. Age-matched, sham-operated animals were used as controls. PASMC K+ currents and membrane potentials were recorded using amphotericin B-perforated patch-clamp techniques. The increase in whole cell current normally seen in response to normoxia was decreased (333.9 +/- 63.6% in control vs. 133.1 +/- 16.0% in hypertensive fetuses). The contribution of the K(Ca) channel to the whole cell current was diminished in hypertensive, compared with control, fetal PASMC. In PASMC from hypertensive fetuses, a change from hypoxia to normoxia caused no change in membrane potential compared with a -14.6 +/- 2.8 mV decrease in membrane potential in PASMC from control animals. In PASMC from animals with pulmonary hypertension, 4-aminopyridine (4-AP) caused a larger depolarization than iberiotoxin, whereas in PASMC from control animals, iberiotoxin caused a larger depolarization than 4-AP. These data confirm the hypothesis that the contribution of the K(Ca) channel to membrane potential and O2 sensitivity is decreased in an ovine model of PPHN, and this may contribute to the abnormal perinatal pulmonary vasoreactivity associated with PPHN.
4-Aminopyridine↗
Measurement of the sieve tube membrane potential.
A procedure is described for the measurement of the sieve tube membrane potential in the phloem of bark strips from Salix exigua Nutt. Measurements were made by inserting a measuring microelectrode into sap exuding from severed stylets of the willow aphid, Tuberolachnus salignus. Data taken from 20 bark strips gave an average potential of -155 +/- 9 millivolts. Evidence is presented for an electrogenic component of the sieve tube membrane potential. The occurrence of a saturable sucrose-induced membrane depolarization is consistent with the concept of sugar accumulation by a sucrose/H(+) co-transport mechanism.
Journal Article↗
Insulin does not act by causing a change in membrane potential or intracellular free sodium and potassium concentration of adipocytes.
The influence of insulin on the intracellular free sodium and potassium ion concentrations ([Na+]i, [K+]i) and resting membrane potential of rat epididymal adipocytes was examined to determine its potential for mediating insulin's action on other cellular processes. Direct intracellular measurements of [Na+]i, [K+]i, and the resting membrane potential were made using ion-selective and conventional microelectrodes. The use of these microelectrodes enabled us to continuously monitor these parameters in the same cell before, during, and after periods of insulin stimulation of up to 20-min duration. The electrical potentials measured in these experiments remained unchanged when the cells were stimulated with insulin (0.01, 0.1, or 1.0 mU/ml). Varying the extracellular glucose concentration had no effect on these results. Our results provide the first direct measurement of [Na+]i and [K+]i in adipose tissue and clearly demonstrate that the response to insulin's association with its receptors on the cell surface and subsequent action on hexose transport and cellular metabolism does not involve a change in membrane potential or intracellular sodium and potassium ions.
Adipose Tissue↗
Osmolality influences bistability of membrane potential under hypokalemic conditions in mouse skeletal muscle: an experimental and theoretical study.
The membrane potential in mouse skeletal muscle depends on both extracellular osmolality and potassium concentration. These dependencies have been related to two membrane transporters, Na+/K+/2Cl- co-transporter and the inward potassium rectifier channel. To investigate the relation of the Na+/K+/2Cl- co-transporter and the inward potassium rectifier channel in a qualitative way, a combined electrophysiological and modelling approach was used. The experimental results show that the bistability of the membrane potential, which is related to the conductive state of the inward potassium rectifier channel, is shifted to higher extracellular potassium values when medium osmolality is increased. These results are confirmed by the computer simulation calculations for increased co-transporter flux. The combined results indicate that the co-transporter is capable of modulating the conductive state of the inward potassium rectifier channel.
Animals↗
Membrane potentials, electrolyte contents, cell pH, and some enzyme activities of fibroblasts.
The resting membrane potential of the cultured fibroblasts derived from rabbit subcutaneous tissues was -10.2 +/- 0.20 mV (n = 390). This potential was affected by the potassium concentration in the culture medium, but not by other chemical or hormonal preparations, such as dibutyryladenosine 3',5'-cyclic monophosphate (0.5 to 5.0 mmol/l), sodium fluoride (10(-5) to 10(-4) M), hydrocortisone (10(-7) to 10(-6) M), parathyroid extract (0.5 to 1.0 U/ml), or thyrotrophin (5 to 10 mU/ml). The Na+, K+, and Cl- concentrations of the cultured fibroblasts were 35.4, 85.7, and 22.6 mmol/l cell water, respectively. The water and protein contents of these cells were 82.1 and 9.18 g/100-g cells, respectively. The intracellular pH of fibroblasts as determined by [14C] dimethyloxazolidine-2, 4-dione, and 3H2O ranged between 6.9 and 7.1 when the pH of the culture medium was maintained at 7.4. The activities of Na+, K+-, HCO3(-)-, and Ca++, Mg++-ATPases in these cultured cells were 19.0 +/- 2.1, 13.6 +/- 2.1, and 6.6 +/- 1.2 nmol pi/mg protein per minute, respectively, and the carbonic anhydrase activity was 0.054 U/mg protein. Calculations based on the values for the membrane potential and the electrolyte concentrations observed in this study indicate that Na+, K+, Cl-, and H+ are not distributed according to their electrochemical gradients across the cell membrane. Na+, Cl-, and H+ are actively transported out of the cells and K+ into the cells.
Adenosine Triphosphatases↗
Changes in membrane potential of cultured porcine and human thyroid cells in response to thyrotrophin and other agents.
Thyrotrophin (TSH), cyclic AMP, cyclic GMP and 1-methyl-3-isobutyl-xanthine (MIX) promoted the reassociation of isolated porcine and human thyroid cells into follicular structures in culture and stimulated the uptake of radio-iodide. Monolayer cells were present in all cultures, but in decreasing proportions as the concentration of stimulator was increased. The resting membrane potential of porcine thyroid cells cultured for 4 days in the presence of TSH was -54 +/- 3.6 (mean +/- S.D.) mV for follicular cells and -31 +/- 2.6 mV for monolayer cells. In the absence of TSH, only monolayer cells were present and their membrane potential was -24 +/- 2.0 mV. Removal of hormone by washing resulted in hyperpolarization to -70 +/- 2.9 mV (follicular cells) or -59 +/- 3.4 mV (monolayer cells). Subsequent replacement of TSH, or addition of cyclic AMP, MIX, prostaglandin E1 (PGE1) or long-acting thyroid stimulator immunoglobulin resulted in depolarization of previously hyperpolarized cells, to approximately the membrane potential observed before washing. Incubation in MIX resulted in enhanced sensitivity to the depolarizing effect of TSH. Cells cultured in the absence of TSH were unresponsive to TSH or other stimulators. The membrane potential of human thyroid cells behaved similarly in response to TSH, to hormone removal and replacement, and to MIX and PGE1.
1-Methyl-3-isobutylxanthine↗
Contribution of the hyperpolarization-activated current to the resting membrane potential of rat nodose sensory neurons.
1. The voltage- and time-dependent characteristics of the hyperpolarization-activated current (IH) and its contribution to the resting membrane potential of neonatal rat nodose sensory neurons were investigated using the whole-cell tight seal method of voltage and current clamp recording. 2. IH was found in all neonatal nodose neurons in vitro, contrary to previous reports where its presence was particular for A-type neurons. We used the presence of both tetrodotoxin-sensitive (TTX-S) and tetrodotoxin-resistant (TTX-R) sodium currents to distinguish C- from A-type neurons (TTX-S only). We obtained further support for the presence of IH in C-type neurons with experiments in which IH was demonstrated in a subset of neurons sensitive to capsaicin. 3. In both groups IH activated at potentials negative to -50 mV, developed slowly with time and was inhibited by 1-5 mM extracellular caesium. At -120 mV, IH activated with a fast time constant of 73 +/- 3 ms in A-type neurons and 163 +/- 37 ms in C-type neurons (P < 0.05). A second, slower time constant of 682 +/- 83 ms was observed in A-type neurons and 957 +/- 122 ms in C-type neurons. 4. A- and C-type neurons differed in the amplitude of IH. The mean magnitude of IH at -110 mV was -2338 +/- 258 pA in A-type neurons but only -241 +/- 40 pA (P < 0.001) in C-type neurons. This disparity persisted when currents were normalized for capacitance. The reversal potentials for IH were -39 +/- 4 mV for A-type neurons and -37 +/- 5 mV for C-type neurons (P > 0.05). 5. During current clamp recording IH caused time-dependent rectification in response to hyperpolarizing current injections from the resting membrane potential. CsCl abolished the rectification and hyperpolarized the resting potential of A-type neurons from -55 +/- 3 mV to -61 +/- 4 mV and C-type neurons from -62 +/- 2 mV to -71 +/- 3 mV. Taken together, the results in these studies indicate that IH contributes to the resting membrane potential in all nodose neurons.
Animals↗
Indications for acceleration-dependent changes of membrane potential in the flagellate Euglena gracilis.
The effects of the calcium sequester EGTA on gravitactic orientation and membrane potential changes in the unicellular flagellate Euglena gracilis were investigated during a recent parabolic-flight experiment aboard of an Airbus A300. In the course of a flight parabola, an acceleration profile is achieved which yields subsequently about 20 s of hypergravity (1.8 g(n)), about 20 s of microgravity, and another 20 s of hypergravity phases. The movement behavior of the cells was investigated with real-time, computer-based image analysis. Membrane potential changes were detected with a newly developed photometer which measures absorption changes of the membrane potential-sensitive probe oxonol VI. To test whether the data obtained by the oxonol device were reliable, the signal of non-oxonol-labelled cells was recorded. In these samples, no absorption shift was detected. Changes of the oxonol VI signals indicate that the cells depolarize during acceleration (very obvious in the step from microgravity to hypergravity) and slightly hyperpolarize in microgravity, which can possibly be explained with the action of Ca-ATPases. These signals (mainly the depolarization) were significantly suppressed in the presence of EGTA (5 mM). Gravitaxis in parallel was also inhibited after addition of EGTA. Initially, negative gravitaxis was inverted into a positive one. Later, gravitaxis was almost undetectable.
Acceleration↗
Proton slippage in cytochrome c oxidase of Paracoccus denitrificans. Membrane-potential measurements with the two-subunit and three-subunit enzyme.
Isolated cytochrome c oxidase from Paracoccus denitrificans, containing either two or three subunits, was reconstituted into liposomes and the membrane potential was measured at different rates of respiration using a triphenylmethylphosponium bromide electrode. Both enzymes revealed a non-linear increase of the membrane potential with increasing respiratory rates. The ratios of the respiratory rates of the two proton pumps decreased with increasing membrane potential, suggesting slippage of proton pumping, as has been shown before with two cytochrome c oxidases from bovine heart, differing in H+/e- stoichiometries due to chemical modification [Steverding, D. & Kadenbach, B. (1991) J. Biol. Chem. 266, 8097-8101]. The data suggest that slippage of proton pumping represents an intrinsic property of cytochrome c oxidase associated with the two catalytic subunits, I and II.
Electron Transport Complex IV↗
A theory for the membrane potential of living cells.
We give an explicit formula for the membrane potential of cells in terms of the intracellular and extracellular ionic concentrations, and derive equations for the ionic currents that flow through channels, exchangers and electrogenic pumps. We demonstrate that the work done by the pumps equals the change in potential energy of the cell, plus the energy lost in downhill ionic fluxes through the channels and exchangers. The theory is illustrated in a simple model of spontaneously active cells in the cardiac pacemaker. The model predicts the experimentally observed intracellular ionic concentration of potassium, calcium and sodium. Likewise, the shapes of the simulated action potential and five membrane currents are in good agreement with experiment. We do not see any drift in the values of the concentrations in a long time simulation, and we obtain the same asymptotic values when starting from the full equilibrium situation with equal intracellular and extracellular ionic concentrations.
Action Potentials↗
The effects of caffeine on sodium transport, membrane potential, mechanical tension and ultrastructure in barnacle muscle fibres.
1. The effects of graded concentrations of caffeine on the Na efflux were investigated. External application of 10 mM caffeine usually caused a biphasic response, viz. a fall, followed by a rise in the Na efflux. 1 and 5 mM caffeine usually caused stimulation. Only the stimulatory phase of this response depended on the presence of external Ca(2+).2. Internal application of 100 mM caffeine caused a small rise in the Na efflux, the magnitude of which was independent of external Ca(2+) and comparable to that obtained with external application of 1 mM caffeine. This action, however, could be greatly augmented by pre-treating the fibre with 5 x 10(-5)M ouabain.3. The rise in Na efflux caused by external application of 10 mM caffeine could be greatly augmented by pre-treating the fibre with 5 x 10(-5)M ouabain. The observed stimulatory response was biphasic, more so in the absence of external Ca(2+). Restoration of external Ca(2+) following the onset of the second stimulatory phase resulted in further rise of the Na efflux. Measurements of the Na efflux during treatment with graded concentrations of ouabain and 10 mM caffeine showed that the rate coefficient for Na efflux varied with the ouabain concentration in the range 10(-8)-10(-4)M. Measurements of the ouabain-insensitive Na efflux before and during treatment with 10 mM caffeine in bathing media containing varying concentrations of Ca, disclosed the existence of two Ca(2+)-thresholds, one in the 0-2.5 mM range and the other in the 12.5-15 mM range.4. Comparisons were made between the effects on the Na efflux of 10 mM caffeine followed by external acidification, and external acidification, followed by 10 mM caffeine. The magnitude of the response of the ouabain-insensitive Na efflux to external acidification before treatment with 10 mM caffeine was greater than that found when external acidification followed external application of the alkaloid. It also was considerably greater than that of the response to external application of 10 mM caffeine before external acidification.5. External application of 10 mM procaine prevented 10 mM caffeine from stimulating the Na efflux, and from inducing contractures. Internal application of 100 mM-EGTA reduced the response of the Na efflux to 10 mM caffeine, and also prevented the fibre from contracting. External application of 10(-4)M diphenylhydantoin reduced the response of the Na efflux to 10 mM caffeine but failed to prevent the development of contractures.6. Internal application of 0.05 M-cGMP, cAMP or its dibutyryl derivative caused a large rise in the Na efflux. The magnitude of the effects observed in ouabain-poisoned fibres was often greater than that in unpoisoned fibres. Internal application of 2.5 units/ml. phosphodiesterase beforehand failed to reduce the magnitude of the stimulatory response to injected cyclic nucleotides. Injected phosphodiesterase also failed to reduce the response of the Na efflux to 10 mM caffeine.7. External application of 10 mM caffeine to unpoisoned and ouabain-poisoned fibres caused a fall of approximately 10 mV in the membrane potential. In unpoisoned fibres this effect was transitory. The response of the membrane potential to internal application of graded concentrations of CaCl(2) was biphasic. When low concentrations of CaCl(2) were used the membrane potential underwent a small rise but when high concentrations were used the opposite was found. These results could not be repeated with graded concentrations of MgCl(2).8. The effects of graded concentrations of caffeine on tension development were also studied. Strong contractures were observed with caffeine concentrations as low as 4 mM, while peak tetanus tension was usually exceeded with 7-8 mM concentrations. The tension-external Ca(2+) curve was sigmoidal in shape.9. Electron microscopic studies showed that 10 mM caffeine in ASW caused little or no distension and disorganization of cisternal fine structure. Such structural changes, however, were far more pronounced in fibres suspended in Ca(2+)-free ASW and then treated with 10 mM caffeine in Ca(2+)-free ASW. Fibres soaked in Ca(2+)-free ASW had ruptured mitochondria and mitoplasts, whereas those additionally treated with 10 mM caffeine had relatively intact mitochondria.10. The main conclusions drawn from this work are: (i) that caffeine stimulates the ouabain-insensitive Na efflux (and inhibits the transport enzyme) by raising the internal free Ca(2+) concentration; (ii) that in the presence of inhibition of the transport enzyme, the magnitude of the stimulatory response to 10 mM caffeine depends not only on the external Ca(2+) concentration but mainly on the residual level of activity of the transport enzyme; (iii) that the Ca(2+)-sensitive and CO(2)-sensitive components of the ouabain-insensitive Na efflux, though not the same, may overlap at the level of the plasma membrane or share a common metabolic step away from the membrane; (iv) that cyclic nucleotides participate in the control of the magnitude of the ouabain-insensitive Na efflux, and that the phosphodiesterase system under the present experimental conditions does not seem to be involved in the mechanism underlying the stimulatory action of caffeine; (v) that the membrane potential changes caused by caffeine fail to explain the stimulatory response of the Na efflux, as well as contracture of these fibres; (vi) that the contractile machinery in these fibres is considerably more sensitive to caffeine than that in vertebrate muscle and the muscles of other arthropods, and (vii) that the Ca(2+) released by the sarcoplasmic reticulum which leads to a biphasic response of the Na efflux is the result of cisternal disorganization caused by caffeine.
Acetates↗
Determination of membrane potentials in human and Amphiuma red blood cells by means of fluorescent probe.
1. Changes in the fluorescent intensity of the dye, 3,3'-dihexyl-2,2'-oxacarbocyanine, added to suspensions of human and Amphiuma red blood cells were measured in parallel with changes in the membrane potentials of these cells. In these studies the membrane potential was altered in three different ways: by the addition of valinomycin to alter the ratio, P(K)/P(Cl), by a change in the pH of the medium to alter the ratio, Cl(c)/Cl(0), and by the substitution of impermeant anions for Cl(0) again to alter the ratio, Cl(c)/Cl(0). In each case hyperpolarization led to a decrease and depolarization to an increase in fluorescent intensity.2. The change in fluorescence with the addition of valinomycin was dependent on the concentration of K in both the cells and the medium. Changes in fluorescence were not observed when valinomycin was added to suspensions of frozen-thawed, haemoglobin-free ghosts with dye in KCl or NaCl solutions. Such changes were observed with reconstituted ghosts provided that there was a K concentration gradient across the membrane.3. From values of cellular K and the corresponding external K concentrations for which there were no changes in fluorescence with valinomycin, estimations of membrane potentials were made. The potential was -5 to -8 mV for the human red cell and -19 mV for Amphiuma. These values are in good agreement with the potentials estimated from the Cl ratios (-9 mV for human and -17 to -20 mV for Amphiuma) and from those obtained by direct electrical measurements (-15 mV for Amphiuma).4. Fluorescent intensity of the dye in suspensions of human red cells was shown to be a linear function of the log Cl(c)/Cl(0).5. The dye (2.9 x 10(-6)M) increased the inward rate constants for (24)Na (3-4-fold) and (42)K (0.5-2-fold) for human red cells. In addition, the dye was found to be haemolytic (5-6% in 1 hr) at 22 degrees C.6. In contrast, the dye did not alter the rate of (35)SO(4) efflux at 37 degrees C from human red cells previously equilibrated with a Cl-free SO(4) medium.7. The dye was also seen to interact with certain impermeant anions and other compounds, e.g. inhibitors of anion permeability, of interest. These interactions and other limitations of the use of this dye are discussed.
Animals↗
Quantitative measurement of cationic fluxes, selectivity and membrane potential using liposomes multilabelled with fluorescent probes.
Liposomes of egg PC/PG (8:2, mol/mol) were multilabelled with PBFI, pyranine and oxonol VI, fluorescent probes for, respectively, K+, H+ and membrane potential. Monitoring fluorescence with a multichannel photoncounting spectrofluorometer during K+ filling experiments allowed to measure K+ influx, the associated H+ efflux and the membrane potential, continuously and simultaneously. The proton net efflux quantitatively mirrored the K+ net influx. The rate of the K+/H+ exchange diminished progressively as a quasi-equilibrium was reached for both K+ and H+. In the presence of valinomycin, the measured membrane potential during the K+ filling actually corresponded to the Nernst potential calculated from the observed K+ gradient. In the absence of valinomycin, it corresponded to the Nernst potential calculated from the observed H+ gradient. In the latter case, the permeability coefficient of liposomes to K+, calculated from the Goldman-Hodgkin-Katz relation, was 6.10(-13) m s-1. The selectivity sequence for alkali cations of liposomes was determined from the measured H+ efflux associated to the influx of the different cations. The selectivity sequence corresponded to the series VI of Eisenman, suggesting interaction of the cation with an anionic field of intermediate strength.
Arylsulfonates↗
Effect of hydralazine on tension and membrane potential in the rat caudal artery.
To determine whether the vasodilator, hydralazine (HYD), produces hyperpolarization of vascular muscle cells, we measured the effect of HYD on membrane potential and contractile responses to phenylephrine and K+. HYD (1 microM) caused a 4 mV hyperpolarization of phenylephrine-depolarized arteries (compared with controls without HYD), which could possibly account for up to three-fourths of the 39% decrease in tension measured. K+-contracted vessels were also 34% relaxed by 1 microM HYD without an effect on membrane potential. In addition, HYD further relaxed phenylephrine-stimulated vessels previously relaxed by D-600, suggesting that Ca++ channel blockade may not be an important mechanism of vasodilation for HYD. The evidence suggests that a nonmembrane action of HYD on arterial muscle probably multiplies the relaxant effect of membrane potential hyperpolarization. Both mechanisms would attenuate the effects of adrenergic stimulation.
Animals↗
The effect of juglone on the membrane potential and whole-cell K+ currents of human lymphocytes.
Using flow cytometric membrane potential measurements with the oxonol dye, we determined that 5.7-57 microM juglone depolarizes human lymphocytes in a dose dependent manner. The depolarizing effect of juglone was verified by patch-clamp. Juglone decreased whole-cell n-type K+ currents in human peripheral blood lymphocytes and accelerated inactivation; however, it did not influence the kinetics of activation of the K+ conductance. The percentage increase in K+ channel inactivation rate and the degree of drug induced block was independent of membrane potential, K+ channel block by juglone fully developed within 4 minutes and was not removable by washing with drug free extracellular solution. Blocking of n-type K+ channels by juglone is in concert with its depolarizing effect on human lymphocytes.
Cytotoxins↗
Assessment of membrane potential changes using the carbocyanine dye, diS-C3-(5): synchronous excitation spectroscopy studies.
The fluorescence of the voltage sensitive dye, diS-C3-(5), has been analyzed by means of synchronous excitation spectroscopy. Using this rather rare fluorescence technique we have been able to distinguish between the slightly shifted spectra of diS-C3-(5) fluorescence from cells and from the supernatant. It has been found that diS-C3-(5) fluorescence in the supernatant can be selectively monitored at lambda exc = 630 nm and lambda em = 650 nm, while the cell associated fluorescence can be observed at lambda exc = 690 nm and lambda em = 710 nm. A modified theory for the diS-C3-(5) fluorescence response to the membrane potential is presented, according to which a linear relationship exists between the logarithmic increment of the dye fluorescence intensity in the supernatant, 1n I/I degrees, and the underlying change in the plasma membrane potential, delta psi p = psi p - psi p degrees. The theory has been tested on human myeloid leukemia cells (line ML-1) in which membrane potential changes were induced by valinomycin clamping in various K+ gradients. It has been demonstrated that the membrane potential change, delta psi p, can be measured on an absolute scale.
Benzothiazoles↗
17beta-estradiol stimulates MAPK signaling pathway in human lens epithelial cell cultures preventing collapse of mitochondrial membrane potential during acute oxidative stress.
17beta-estradiol (17beta-E2) protects against H2O2-mediated depletion of intracellular ATP and lessens the degree of depolarization of mitochondrial membrane potential (DeltaPsi(m)) in cultured lens epithelial cells consequential to oxidative insult. We now report that 17beta-E2 acts as a positive regulator of the survival signal transduction pathway, MAPK which, in turn, acts to stabilize DeltaPsi(m) in effect, attenuating the extent of depolarization of mitochondrial membrane potential in the face of acute oxidative stress. The SV-40 viral transformed human cell line, HLE-B3 was treated with 17beta-E2 over a time course of 60 min and phosphorylation of ERK1/2 was analyzed by Western blot. ERK1/2 was phosphorylated within 5-15 min in the presence of 17beta-E2. Cell cultures were exposed to the MEK1/2 inhibitor, UO126, subsequent to H2O2+/-17beta-E2 treatment and the DeltaPsi(m) examined using JC-1, a potentiometric dye which serves as an indicator for the state of mitochondrial membrane potential. UO126 treatment attenuated ERK1/2 phosphorylation irrespective of whether estradiol was administered. Mitochondrial membrane depolarization resulting from H2O2 stress was substantially greater in the presence of UO126. The greater the extent of depolarization, the less effective 17beta-E2 treatment was in checking mitochondrial membrane depolarization, indicating that the relative degree of ERK phosphorylation influences mitochondrial stability with oxidative insult. The data support a positive correlation between 17beta-E2 stimulation of ERK1/2 phosphorylation and mitochondrial stabilization that would otherwise cause a complete collapse of DeltaPsi(m).
Animals↗