Large Transient Increase Research Articles

Simple spike responses of gaze velocity Purkinje cells in the floccular lobe of the monkey during the onset and offset of pursuit eye movements.

1. We recorded the simple spike firing rate of gaze velocity Purkinje cells (GVP-cells) in the flocculus/ventral paraflocculus of two monkeys during the smooth pursuit eye movements evoked by a target that was initially at rest, started suddenly, moved at a constant velocity, and then stopped. 2. For target motion in the preferred direction, GVP-cells showed a large transient increase in firing rate at the onset of pursuit, a smaller but sustained increase during the maintenance of pursuit, and a smooth return to baseline firing with little undershoot at the offset of pursuit. For target motion in the nonpreferred direction, GVP-cells showed a small decrease in firing rate at the onset of pursuit, a similar sustained decrease during the maintenance of pursuit, but a large transient increase in firing rate at the offset of pursuit before returning to baseline firing. 3. We pooled the data in our sample of horizontal GVP-cells by subtracting the population average of firing rate recorded during pursuit in the nonpreferred direction from the population average recorded during pursuit in the preferred direction. We transformed this net population average by passing it through a model of the brain stem final common pathway and the oculomotor plant. This yielded a signal that closely matched the observed trajectory of eye velocity during pursuit. We conclude that the transient overshoots exhibited in the firing rate of GVP-cells can provide appropriate compensation for the lagging dynamics of the oculomotor plant.

Spontaneous Ca2+ release from a caffeine and ryanodine-sensitive intracellular Ca2+ store in freshly prepared hepatocytes

A considerable fraction of freshly prepared hepatocytes loaded with the fluorescent [Ca2+]i indicator fura-2 exhibited spontaneous rhythmic fluctuations that tended to decrease with increasing length of incubation after isolation. These oscillations were dependent on the external Ca2+. They could no longer be observed when a Ca2+ chelator-(ethylenebis [oxyethylenenitrilo]) tetraacetic acid--was added to medium. Addition of thapsigargin, which is known to release Ca2+ from inositol 1,4,5-trisphosphate-sensitive and -insensitive Ca2+ stores, induced a large transient increase in [Ca2+]i and abolished the fluctuations. When the cells were treated with 2 mmol/L caffeine, frequency was increased, whereas 10 mmol/L caffeine induced a single large peak followed by a persistent plateau. Moreover, addition of dibutyryl cAMP led to decreased frequency of fluctuations. Ryanodine caused larger fluctuations; thereafter the [Ca2+]i level became much higher and the spikes ceased. These results suggest that spontaneous rhythmic fluctuations in freshly prepared hepatocytes are driven by Ca2+ release from a caffeine- and ryanodine-sensitive calcium-induced calcium release pool.

19F nuclear magnetic resonance studies of free calcium in heart cells

19F nuclear magnetic resonance is used in conjunction with 5,5'-difluoro-1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (5FBapta), a fluorinated calcium chelator, to report steady-state intracellular free calcium levels ([Ca2+]i) in populations of resting, quiescent, isolated adult heart cells. 31P nuclear magnetic resonance shows that 5FBapta-loaded cells maintain normal intracellular high-energy phosphates, pH, and free Mg2+. The intracellular free calcium concentration of well perfused, isolated heart cells is 61 +/- 5 nM, measured with 5FBapta, which has a dissociation constant (Kd) for calcium chelation of 500 nM. A similar value is obtained with Quin-MF, another fluorinated calcium chelator with Kd and maximum calcium sensitivity at 80 nM. We find that the steady-state level of intracellular free calcium is increased by decreased extra-cellular sodium concentration, omission of extracellular magnesium, decreased extracellular pH, hyperglycemia, and upon treatment with lead acetate. Further, extracellular ATP caused a large transient increase in [Ca2+]i. Thus, while heart cells maintain a very low level of intracellular free Ca2+, acute alterations in extracellular environment can cause derangement of calcium homeostasis, resulting in measurable increases in [Ca2+]i.

Importance of tonicity of carbicarb on the functional and metabolic responses of the acidotic isolated heart

In this study, the physiological and metabolic effects of Carbicarb administered as an isotonic (150 mmol/L Na [n|]l+) or hypertonic (1 mol/L Na [n|]l+) solution over 2 minutes in the acidotic isolated heart were compared. Physiological monitoring as well as 31P and 23Na nuclear magnetic resonance spectroscopy were performed. Both isotonic and hypertonic Carbicarb induced comparable dose-dependent increases in intracellular pH as well as decreases in inorganic phosphate and increases in creatine phosphate concentrations, which were sustained for 20 minutes. However, immediate functional improvement was greater in hearts receiving isotonic Carbicarb. Metabolic acidosis conditions resulted in a 27% increase in cytosolic sodium by 30 minutes ( P < .05). In this setting, hypertonic Carbicarb induced a large transient increase in cytosolic sodium, whereas isotonic Carbicarb caused immediate and sustained decreases in cytosolic sodium. These data suggest that isotonic Carbicarb may have more beneficial effects on cardiac function than hypertonic Carbicarb. These effects may be related to associated changes in cytosolic sodium.

Differences in Ca2+ mobilization by muscarinic agonists in tracheal smooth muscle

The muscarinic agonists acetylcholine (ACh) and McN-A-343 activate a homogeneous population of M3 receptors in canine tracheal smooth muscle. However, ACh is much more efficacious than McN-A-343 both at stimulating force development and active shortening and at antagonizing relaxation induced by isoproterenol. In other tissues, the same muscarinic receptor may be coupled to multiple subcellular pathways, but activate different pathways depending on the efficacy of the agonist. The present study investigated mechanisms of excitation-contraction coupling in canine tracheal smooth muscle by muscarinic agonists of different efficacy. ACh was more effective at stimulating inositol phosphate production and elicited a large initial transient increase in intracellular Ca2+ concentration ([Ca2+]i), whereas McN-A-343 elicited only a slow gradual rise in [Ca2+]i. Extracellular Ca2+ influx through voltage-operated channels played a minor role in contractions induced by either agonist. Results suggest that contractions by ACh and McN-A-343 may be mediated by the same subcellular pathways; however, the greater potency of ACh at stimulating those pathways results in very different kinetics of Ca2+ activation.

Effect of quinine on autoreceptor-regulated dopamine release in the rat striatum.

In vivo brain microdialysis was used to examine the role of potassium channel activation in dopamine (DA) autoreceptor function in the striatum of freely moving rats. Local application of the D2 receptor agonists quinpirole or N-0437 through the dialysis probe significantly reduced extracellular concentrations of DA. Local application of the D2 antagonist (-)-sulpiride produced significant increases in DA. Local perfusion with quinine, a K+ channel blocker, completely blocked the (-)-sulpiride-induced increases in DA but did not affect the DA agonist-induced decreases. (-)-Sulpiride completely blocked the effect of quinpirole on DA both in control and in quinine-treated animals. At the highest dose used, quinine caused a large transient increase in extracellular DA. Local application of tetrodotoxin or infusion of Mg2+ in the absence of Ca2+ did not prevent this quinine-induced transient increase in extracellular DA. These results demonstrate that DA autoreceptors in the striatum regulate DA release in awake, behaving animals. Local application of (-)-sulpiride increases DA levels by blocking the tonic activation of autoreceptors by endogenous DA. Quinine blocks the neuroleptic-induced increase in DA, perhaps by preventing the K+ channel opening that would normally accompany endogenous autoreceptor activation. The fact that exogenously applied DA receptor agonists can decrease extracellular DA levels in the presence of quinine suggests that they may be acting at extrasynaptic autoreceptors that are not tonically active in vivo. The effect of DA agonists on this site is via a DA receptor because it is blocked by (-)-sulpiride. However, this receptor does not appear to be coupled to a quinine-sensitive potassium channel.

Wrong‐way behavior of packed‐bed reactors: Influence of reactant adsorption on support

AbstractWrong‐way behavior refers to a large transient temperature increase caused by a sudden reduction in the feed temperature or increase in the feed rate to a packed‐bed reactor operating at an intermediate or high level of conversion. This dynamic temperature rise may be affected by reactant adsorption on the inert catalyst support. The wrong‐way behavior usually leads to formation of a downstream‐moving temperature front. In such cases, reactant adsorption tends to moderate and decrease the maximal transient temperature of these fronts. However, when the wrong‐way behavior generates an upstream‐moving temperature front, reactant adsorption may substantially increase the temperature rise over that attained in its absence and ignite the reactor. Reactant adsorption may also lead to surprising dynamic effects upon changes in feed velocity.

Thapsigargin activates a calcium influx pathway in the unfertilized mouse egg and suppresses repetitive calcium transients in the fertilized egg.

At fertilization, the sperm initiates development of the mouse egg by inducing a large transient increase in the intracellular Ca2+ concentration ([Ca2+]i), which is followed by repetitive transient increases in [Ca2+]i. To determine how the repetitive Ca2+ transients are produced, thapsigargin, an inhibitor of the endoplasmic reticulum Ca-ATPase, was used to deplete intracellular Ca2+ stores within the egg. In the unfertilized egg, thapsigargin (1-50 microM) caused a slowly rising and falling transient increase in [Ca2+]i with or without extracellular Ca2+. An influx pathway for Ca2+ is activated by thapsigargin, since an immediate increase in [Ca2+]i occurred when Ca2+ was added to eggs after thapsigargin treatment in a Ca2+, Mg(2+)-free medium. This suggests that Ca2+ entry in the mouse egg may be coupled to the emptying of an intracellular store. The magnitude of the first Ca2+ transient at fertilization was reduced by as much as 84% in eggs pretreated with thapsigargin. Reduction of extracellular Ca2+, by addition of a Ca2+ chelator, suppressed the repetitive Ca2+ transients following fertilization. The Ca2+ transients also require filling of an intracellular store; they were suppressed when thapsigargin was added before or after fertilization. These results support the hypothesis that the first sperm-induced Ca2+ transient at fertilization depletes an intracellular Ca2+ store, triggering an increase in plasma membrane Ca2+ permeability, and that the enhanced Ca2+ influx causes repetitive Ca2+ transients due to the periodic filling and emptying of an intracellular Ca2+ store.

Is there a calcium paradox in isolated bovine aortic endothelial cells?

When bovine aortic endothelial (BAE) cells are superfused with a solution containing low calcium (approximately 10 nM) and subsequently exposed to a solution containing normal Ca2+ (2 mM) a large transient increase in intracellular calcium is seen. This elevation in [Ca2+]i is similar to that described as the calcium paradox in cardiac cells. If the cells are exposed to the agonist, ATP, during the period in low-Ca2+ solution the paradoxical rise in [Ca2+]i is increased. Removal of external Na+ from the low-Ca2+ solution reduces the rise in [Ca2+]i on returning to 2mM-Ca2+ solution. These data are consistent with the presence of a calcium paradox in these cells and with the hypothesis that the underlying mechanism involves the loading of the cell with Na+ during the period in low Ca2+. This process may occur as a result of the altered selectivity of the ATP-activated Ca2+ influx mechanism.

Effects of inorganic phosphate on calcium and tension oscillations in saponin-treated rat cardiac muscle.

The effects of inorganic phosphate (Pi) on the sarcoplasmic reticulum (s.r.) were studied in saponin-treated rat cardiac muscle. Ca2+ -uptake and release by the s.r. was detected using Indo-1. Oscillations of Ca2+ and tension occurred when the [Ca2+] of the bathing solution was around the threshold for force production. Introduction of Pi (20mM) caused a slow transient release of Ca2+ from the s.r. The oscillations were abolished in the presence of Pi. Removal of Pi caused a rapid fall in Ca2+ followed by a large transient increase in [Ca2+] and tension. Results are consistent with a phosphate-induced decrease Ca2+ available for release.

Repetitive calcium transients and the role of calcium in exocytosis and cell cycle activation in the mouse egg

The role of calcium in cortical granule exocytosis and activation of the cell cycle at fertilization was examined in the mouse egg using the calcium chelator BAPTA (1,2-bis( o-aminophenoxy)ethane- N,N,N′,N′-tetraacetic acid) and the fluorescent calcium indicator fluo-3. BAPTA and fluo-3 were introduced into zona-free mouse eggs by a 30-min incubation with 0.01–50 μ M BAPTA acetoxymethyl ester (AM) and/or 1–20 μ M fluo-3 AM prior to in vitro fertilization. Incubation of eggs in ⩾5.0 μ M BAPTA AM inhibited cortical granule exocytosis in all cases. Introduction of the calcium chelator into the egg blocked second polar body formation at ⩾1.0 μ M BAPTA AM. Sperm entry occurred in all eggs regardless of the BAPTA AM concentration. Sperm induce a large transient increase in calcium lasting 2.3 ± 0.6 min, followed by repetitive transients lasting 0.5 ± 0.1 min and occurring at 3.4 ± 1.4-min intervals. Incubation with ⩾5.0 μ M BAPTA AM inhibited all calcium transients. Introduction of BAPTA also inhibited calcium transients, exocytosis, and the resumption of meiosis following application of the calcium ionophore A23187 or SrCl 2, which activate eggs. These results demonstrate that the calcium increase at fertilization is required for cortical granule exocytosis and resumption of the cell cycle in a mammalian egg.

Inhibition of Ca2+ inflow causes an abrupt cessation of growth-factor-induced repetitive free Ca2+ transients in single NIH-3T3 cells

In single NIH-3T3 fibroblasts loaded with fura-2, bombesin induced one of three patterns of increase in the concentration of intracellular free Ca2+ [( Ca2+]i): a single transient increase, a sustained increase, or repetitive transient increases in [Ca2+]i. Foetal-calf serum and ATP also gave these three patterns of response, although a lower proportion of cells gave repetitive Ca2+ transients in response to ATP. An increase in the concentration of bombesin from 1 to 25 nM increased the proportion of cells which exhibited repetitive Ca2+ transients. At 25 nM-bombesin, the proportion of cells which exhibited repetitive Ca2+ transients increased as the extracellular Ca2+ (Ca2+o) concentration was increased from 1 to 5 mM. Removal of Ca2+o by addition of EGTA, or inhibition of Ca2+ inflow by treatment of cells incubated in the presence of Ca2+o with verapamil or an activator of protein kinase C, abruptly terminated repetitive Ca2+ transients, with only one transient observed after the cessation of Ca2+ inflow. Repetitive Ca2+ transients were not observed in cells incubated in the absence of Ca2+o and in the presence of EGTA. Addition of Ca2+o to cells previously incubated in the presence of EGTA caused a resumption of repetitive Ca2+ transients. Addition of thapsigargin alone induced a large transient increase in [Ca2+]i, whereas much smaller transient increases in [Ca2+]i were induced in about 30% of cells tested by caffeine or carbonyl cyanide m-chlorophenylhydrazone (CCCP) plus oligomycin. Thapsigargin or the combination of CCCP plus oligomycin completely inhibited bombesin-induced repetitive Ca2+ transients, whereas caffeine had no effect. It is concluded from the studies of the role of Ca2+o that NIH-3T3 cells differ from other cell types in the anatomical or chemical links between extracellular Ca2+ and the intracellular stores involved in the generation of Ca2+ transients, whereas the results of the experiments with inhibitors indicate that the generation of repetitive Ca2+ transients in NIH-3T3 cells is unlikely to involve Ca(2+)-induced Ca2+ release from caffeine-sensitive stores.

Myo-inositol and betaine transporters regulated by tonicity are basolateral in MDCK cells

Myo-inositol and glycinebetaine are compatible osmolytes accumulated in the renal medulla and in MDCK cells cultured in hypertonic media. Both osmolytes are taken up by MDCK cells on Na-coupled transporters. The maximal velocity (Vmax) of both cotransporters is increased by culture in hypertonic medium. When hypertonic MDCK cells are shifted to isotonic medium there is a large transient efflux of osmolytes. To determine the polarity of the cotransporters and the transient efflux, we grew MDCK cells on a porous support to assay transport separately at their apical and basolateral surfaces. In hypertonic cells, basolateral uptake of both osmolytes was 1) more than 10-fold apical uptake, 2) greater than 96% Na dependent, 3) 25- (myo-inositol) and 16-fold (glycinebetaine) uptake in isotonic cells, reaching a maximum 24 h after the switch to hypertonic medium. When medium osmolarity was decreased from hypertonic to isotonic, myo-inositol uptake reversed to the isotonic level within 1 day; glycinebetaine uptake decreased more slowly. When medium osmolarity was decreased from hypertonic to isotonic, there was a large transient increase in basolateral efflux of both osmolytes.

Intracellular mediators of bombesin action on rat pancreatic acinar cells

The effects of bombesin on physiological responses (amylase secretion, protein synthesis) and intracellular mediators [inositol 1,4,5-trisphosphate (1,4,5-IP3), [Ca2+]i, and diacylglycerol] were studied in isolated rat pancreatic acini and compared with the actions of cholecystokinin (CCK). Bombesin stimulated amylase secretion to the same extent as CCK. However, it failed to reproduce the inhibition of amylase secretion by high concentrations of CCK and likewise did not inhibit incorporation of [3H]leucine into protein in contrast to high concentrations of CCK. Low concentrations of bombesin (1-100 pM) induced repetitive oscillations in [Ca2+]i, whereas higher concentrations of bombesin (1-10 nM) induced a large transient increase in [Ca2+]i followed by a small sustained plateau. Bombesin (1-100 nM) induced an early peak of 1,4,5-IP3 at 5-15 s but was without measurable effect at lower concentrations. These effects on [Ca2+]i and 1,4,5-IP3 were similar to those seen with CCK except that bombesin was approximately 10-fold less potent than CCK. Bombesin induced an increase in acinar 1,2-diacylglycerol with a biphasic time course similar to CCK. However, the magnitude of the response to bombesin was much smaller than the response to CCK. The results suggest that bombesin receptors initiate similar intracellular messengers as does CCK. However, CCK induces a larger increase of diacylglycerol and probably an as yet unidentified messenger responsible for its inhibitory effects.

Ca2+ Dynamics in Rat Pancreatic AR-42J and AR-IP Cells.

Spatiotemporal change of the cytosolic free Ca2+ concentration ([Ca2+]i) in response to a variety of secretagogues was examined in rat pancreatoma AR-42J and AR-IP cells by microspectroflurometry and digital imaging microscopy after loading with fura-2. In the presence of external Ca2+, carbachol, CCK-OP (cholecystokinin-octapeptide), gastrin, norepinephrine or high K+ evoked a large transient increase in [Ca2+]i in AR-42J cells which declined to a sustained level before slowly declining towards the resting level. In the absence of external Ca2+, a transient increase in [Ca2+]i were evoked by all the ligands except for high K+ stimulation, which declined rapidly towards the resting level. The [Ca2+]i increase caused by carbachol and high K+ treatment was inhibited by muscarinic receptor antagonist, atropine, and by L-type Ca2+ channel blocker, nifedipine, respectively. The transient [Ca2+]i increase induced by gastrin stimulation was not blocked by Ca2+ channel blocker, lanthanum. In the AR-IP cells, which are non-differentiated pancreatoma cell line, all stimulations including high K+ treatment have failed to evoke [Ca2+]i response. These intracellular Ca2+ mobilizations in response to ligands in AR-42J cells were displayed by digital imaging microscopy. From these results we conclude that AR-42J cells has an alpha-adrenergic receptor, in addition to muscarinic acetylcholine receptor, CCK-OP receptor, gastrin receptor and voltage dependent Ca2+ channel. In marked contrast, AR-IP cells have neither any hormone receptor for the above ligands nor voltage dependent Ca2+ channel.

Cell cycle and gene expression in the insulin producing pancreatic cell line ?TC1

The pancreatic cell line beta TC1, established from insulinomas of transgenic mice carrying a hybrid insulin-promoted large T antigen gene, has retained several characteristics of normal cells, including the insulin content and inducibility of insulin secreting by glucose. We show here that the growth of beta TC1 cells is arrested in low serum-concentration medium. Cells exposed for three days to 0.25% fetal calf serum ceased to incorporate [3H]thymidine but were still able to resume the cell division cycle upon addition of serum. In this cell line, we have determined by cytofluorometry the cell cycle kinetic parameters to be of 21 h, 10 h 30 min and 12 h for the G1, S and G2/M phases, respectively. Quiescent beta TC1 cells constitutively expressed the protooncogene c-jun that codes for the transcriptional factor AP1, as well as cdc2, another cell cycle-related gene. A large transient increase in the expression of the c-fos gene was obtained rapidly, 30 min after addition of serum and a similar increase in c-jun expression after one hour. Expression of the cdc2 gene was also enhanced to a lesser extent. The same effects were also observed in the presence of cycloheximide, thus proving that the expression of these three genes is directly stimulated by serum growth factors. Consequently, quiescent beta TC1 cells provide a good model for studying the short- and long-term effects of growth factors on Beta-cell proliferation.

3-Hydroxy-3-methylglutaryl Coenzyme A Reductase from Spruce ( Picea abies). Properties and Regulation

Abstract HM GCoA reductase was identified in seedlings, callus cultures, cell suspension cultures and in needles of spruce ( Picea abies) (L.) (Karst). Activity was found in both the 18 K pellet and in the 105 K pellet with different ratios between the two fractions from the various sources. The enzyme has a pH-optimum of 7.9 and an absolute requirement for NADPH . The presence of a thiol reagent such as dithiothreitol is required for activity. Km for HM G CoA is 20 -25 μM. Detergents have differential effects on the activity. In seedlings, enzyme activity was considerably higher in the hypocotyls than in the cotyledons. Enzyme activity was high in dark-grown and low in light-grown seedlings. When the light conditions were reversed, levels of activity adapted to the respective new conditions (increase or decline of specific activity). Aerobic incubations of seedlings, callus cultures or needles in medium containing a carbon source, resulted in a large (up to 20-fold) transient increase of HMGCoA reductase activity. Transfer of stationary phase cell suspension cultures into new medium caused a similarly large increase of activity. A number of carbohydrates induced the enzyme, glucose, fructose and sucrose being most effective. The increase of activity was prevented by cycloheximide. All changes of activity were much more pronounced in the 18 K pellet HMG CoA reductase

Ineffective Thrombopoiesis

In effective thrombopoies is has been inferred to occur in several disease sates from considerations of megakaryocyte mass and platelet kinetics. Microscopic examination has demonstrated increased numbers of megakaryocytes, with a typical forms particularly pronounced, in primary myelofibrosis. It has not been documented if megakaryocyte ever fail to reach maturity in non-pathological situations. A major difficulty of establishing this is that the number of megakaryocytes normally present in the marrow is extremely low. A large transient increase in megakaryocytopoiesis can how ever be induced in mice by an injection of 5-fluorouracil. We have utilised this treatment and report here evidence for in effective thrombopoies is in healthy mice.Adult mice were perfused (2% glutaraldehyde in 0.08M phosphate buffer, pH 7.4) 8 days following an injection of 5-fluorouracil (150mg/kg). Femurs were subsequently decalcified in 10% neutral E.D.T.A. and embedded in Spurrs resin. Transverse sections of marrow revealed many megakaryocytes at various stages of maturity. Occasional megakaryocytes (less than 1%) were found to be under going degeneration prior to achieving full maturation and releasing cytoplasm as platelets. These cells were characterized by a peripheral rim of dense cytoplasm which enveloped a mass of organelles and vacuoles (Fig. 1). Numerous microtubules were foundaround and with in the organelle-rich zone (Fig 2).

Induction of glia-derived nexin after lesion of a peripheral nerve.

Glia-derived nexin (GDN), also known as protease nexin I, is a serine protease inhibitor of deduced relative molecular mass 41,700, identified in conditioned media of glioma cells by its neurite-promoting activity. GDN can promote neurite outgrowth in vitro from neuroblastoma cells, sympathetic neurons and hippocampal neurons (L. Farmer et al., manuscript in preparation). In vivo, GDN is constitutively expressed in all parts of the olfactory system, where axonal regeneration and neurogenesis occur continuously throughout life. This observation indicates that GDN could be important for axonal regeneration in vivo. To investigate this possibility, we have taken advantage of the fact that damage to nerves in the peripheral nervous system leads to their regeneration, whereas in the central nervous system no such regeneration can occur. Here we report that after lesion of the rat sciatic nerve there is a large transient increase in the amount of GDN messenger RNA and of released GDN. The cells showing GDN immunoreactivity are mainly localized distal to the lesion site. These results further support the suggestion that GDN is important for axonal regeneration in vivo, and indicate that protease inhibitors could have a role in Wallerian degeneration and peripheral nerve regeneration.

Changes in the permeability of membranes due to their decompression during permeation

Release of pressure during permeation experiments leads to a large transient increase in the apparent diffusivity of gases. In some systems changes in the diffusivity are coupled with increases in the selectivity. The apparent diffusion coefficients of O 2 and of CO 2 increase by a factor of 35 in natural rubber (NR) membranes and by a factor of 50 (for oxygen) in internally plasticized PVC. This phenomenon is ascribed to transient changes that take place in the membrane as result of a sudden build up of the internal pressure of the dissolved gases. The relaxation constants for the return of the system to equilibrium were calculated to be in the range of 30-50 sec. Improvement of the performance of permeation systems by a cyclic mode of operation, which permits the exploitation of the high flow rates coupled with high selectivities that momentarily may be induced at low pressures is also discussed.