Changes In Transport Rates Research Articles

Modeling carbonate sequence development without relative sea-level oscillations

Research Article| December 01, 2001 Modeling carbonate sequence development without relative sea-level oscillations Peter M. Burgess Peter M. Burgess 1Department of Earth Sciences, University of Cardiff, P.O. Box 914, Main Building, Park Place, Cardiff CF10 3YE, UK Search for other works by this author on: GSW Google Scholar Author and Article Information Peter M. Burgess 1Department of Earth Sciences, University of Cardiff, P.O. Box 914, Main Building, Park Place, Cardiff CF10 3YE, UK Publisher: Geological Society of America Received: 12 Apr 2001 Revision Received: 24 Jul 2001 Accepted: 09 Aug 2001 First Online: 02 Jun 2017 Online ISSN: 1943-2682 Print ISSN: 0091-7613 Geological Society of America Geology (2001) 29 (12): 1127–1130. https://doi.org/10.1130/0091-7613(2001)029<1127:MCSDWR>2.0.CO;2 Article history Received: 12 Apr 2001 Revision Received: 24 Jul 2001 Accepted: 09 Aug 2001 First Online: 02 Jun 2017 Cite View This Citation Add to Citation Manager Share Icon Share Facebook Twitter LinkedIn MailTo Tools Icon Tools Get Permissions Search Site Citation Peter M. Burgess; Modeling carbonate sequence development without relative sea-level oscillations. Geology 2001;; 29 (12): 1127–1130. doi: https://doi.org/10.1130/0091-7613(2001)029<1127:MCSDWR>2.0.CO;2 Download citation file: Ris (Zotero) Refmanager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentBy SocietyGeology Search Advanced Search Abstract Standard conceptual models propose that stratal patterns in carbonate depositional sequences are controlled predominantly by relative sea-level oscillations, even during greenhouse periods when amplitudes of relative sea-level oscillations were small. However, numerical experiments with a two-dimensional forward model of carbonate systems suggest that variations in sediment-transport rate and carbonate productivity are capable of producing similar parasequence stacking patterns, without relative sea-level oscillations. This result suggests two alternative end-member models, one driven by relative sea-level change, the other driven by changes in transport rate and productivity controlled ultimately by climatic factors. Many carbonate systems may represent some combination of these end-member possibilities. You do not have access to this content, please speak to your institutional administrator if you feel you should have access.

In vitro transepithelial drug transport by on-line measurement: Cellular control of paracellular and transcellular transport

Studies on transcellular transport across epithelial cell layers are performed mostly by discontinuous sampling of the transported compound. This has several drawbacks, e.g., it gives disturbances in volume, it limits the time-resolution, and is often laborious. In this report we introduce a method to measure transepi-thelial transport of fluorescent compounds continuously. The time-resolution is at the (sub)minute scale, allowing the measurement of the change in transport rate before and after transport modulation. We will describe how we used the method to measure transcellular and paracellular transport. For highly membrane-impermeable compounds, the paracellular transport and the regulation of the tight junctions was studied in wild-type and MDR1 cDNA transfected epithelial canine kidney cells (MDCKII). The effect of the multidrug transporter P-glycoprotein (Pgp) on the transepithelial transport was studied. Addition of the Pgp inhibitor SDZ PSC 833 showed a modulation of the idarubicin (IDA) and daunorubicin (DNR) transport, which was larger during transport from the basolateral to the apical side than in the reverse direction. By modeling the transepithelial transport, we found that in these cells Pgp had more effect on the basolateral to apical transport than vice versa, which can be attributed to a relatively large passive permeation coefficient for the cellular basolateral plasma membrane.

A Numerical Microphysical Model of the Condensational Venus Cloud

A numerical microphysical model that treats one-dimensional vertical transport of sulfuric acid/water solution aerosols, their nucleation, growth/evaporation, coagulation, and sedimentation, is applied to the condensational middle and lower Venus clouds. The model predicts the vertical profiles of sulfuric acid gas and water vapor, cloud microphysical properties, and the acid concentration of the aerosol particles. Results of model simulations agree favorably with Pioneer Venus particle size spectrometer data, extinction and backscattering coefficients measured by Pioneer Venus and Venera probes,in situand remote observations of cloud optical depth, and sulfuric acid vapor abundances retrieved from Magellan radio occultation data. It is found that the lower Venus cloud is formed as a consequence of a large upward flux of sulfuric acid vapor from the evaporation region below the cloud base. The mechanism of lower cloud formation is probably heterogeneous nucleation of sulfuric acid and water vapors on soluble nuclei. Model altitude profiles of the abundances of water vapor and gaseous sulfuric acid demonstrate the control of these vapors by the condensational cloud. Cloud processes account for the observed decline in concentration of water vapor with altitude, from ≈30 ppm below the clouds to ≈10 ppm at 60-km altitude. The structure of the lower and middle clouds is strongly dependent on the eddy diffusion coefficient. Hence, changes in transport rates may explain the variations in cloud properties revealed by the Pioneer Venus and Venera probein situmeasurements as well as by Earth-based and Galileo near-infrared observations of the lower part of the Venus cloud.

Regulation of Ion Transport in Colonic Crypts

Colonic crypt cells, depending on regulatory influences such as neurotransmitters and hormones, can absorb or secrete NaCl. The large changes in absolute rates of transport, multiplicity of regulatory pathways, and complete reversal of vectorial transport in these cells pose intriguing questions. Some of these questions have been examined recently;most answers came as a complete surprise.

Impedance investigation of the mechanism of copper electrodeposition from acidic perchlorate electrolyte

The mechanism of the copper electrodeposition from acidic perchlorate electrolyte has been investigated with polarization and impedance methods. The impedance of the copper electrode in copper perchlorate electrolytes has been measured as a function of frequency for different E dc overpotential values and different copper(II) ion concentrations. The relations between the shape of a complex plane impedance display and the copper electrode potential values as well as the concentration of Cu II ion were analysed in terms of the electrode reaction mechanism. It is shown, that the presence of the intermediate cuprous ion and its sinusoidal change of transport rate is one of the main factors determining the depressed shape of the impedance arc. The quantitative relation between the faradaic impedance and the rates of electrode reaction rates was established. The impedance arc was simulated with a set of parameters involving: rate constants, Tafel slopes, diffusion coefficient of cuprous ion and double layer capacitance. The rate constants were calculated with respect to E Cu 2 + Cu 0 0 as: k 1 0 = 6.50 × 10 −5 cm s −1, k 2 0 = 0.139 cm s −1, k −2 0 = 1.88 × 10 −7 mol cm −2 s −1.

Oxygen diffusion in a fine‐grained quartz aggregate with wetted and nonwetted microstructures

Oxygen grain boundary and bulk diffusion rates have been measured in a 1.2‐μm grain diameter quartz aggregate (Arkansas novaculite) preannealed in wetting and nonwetting fluids to determine the effect of microstructure. Samples were preannealed at 800°C and 150 MPa confining pressure for 6 to 12 days with pure water, pure CO2, or water + NaCl (∼6M) to produce equilibrium microstructures. The samples were then annealed at 450° to 800°C and 100 MPa confining pressure with 98%18O‐enriched water to determine the diffusion rates. Profiles of18O/(18O+16O) with depth from the surface were measured using an ion microprobe, and the product of the grain boundary diffusion coefficient (D′) and effective boundary width (δ) or the bulk diffusion coefficient (Dbulk) determined. Compared to the starting material, the D′δ values for samples texturally equilibrated with pure CO2(nonwetted microstructure) and pure water are about the same and about 4 times greater, respectively. Bulk diffusivities in samples preannealed with 6MNaCl (wetted microstructure) are 4 to 5 orders of magnitude greater than the bulk diffusivities in samples preannealed with pure CO2(nonwetted). In addition, the D'δ value for a sample texturally equilibrated first with 6MNaCl and then with pure CO2is about a factor of 3 greater than the value for the starting material, demonstrating that the textural equilibration process is essentially reversible. The results of this study indicate that transport rates are strongly influenced by the wetting characteristics of coexisting fluids in a polycrystalline aggregate. In nonwetted samples, changes in the effective grain boundary width or the formation of small isolated pores at triple junctions can change D′δ values. However, these effects are minor compared to the change in transport rate for samples with nonwetted versus wetted microstructures. The much faster rates for samples with a wetted microstructure are believed to be due to oxygen transport along the interconnected channels by ionic diffusion in a static fluid. The bulk diffusivities obtained for samples with a wetted microstructure are consistent with previously determined values for oxygen exchange at an igneous intrusive contact.

The effects of metabolism on Na(+)‐K(+)‐Cl‐ co‐transport in ferret red cells.

1. The effects of altering metabolism on Na(+)-K(+)-Cl- co-transport were studied in ferret red cells. Na(+)-K(+)-Cl- co-transport was measured as the bumetanide-sensitive uptake of 86Rb. 2. Glucose, but not inosine or adenosine, sustained metabolism and maintained cell ATP content ([ATP]i) at the physiological level. [ATP]i could be reduced by prolonged incubation of cells in a substrate-free medium or more quickly by incubating cells with 2-deoxyglucose or with a mixture of iodoacetamide and glucose. 3. Na(+)-K(+)-Cl- co-transport activity was inhibited when [ATP]i was reduced to below 100 mumol (1 cell)-1 by starvation or by treatment with 2-deoxyglucose. However, a unique relationship between [ATP]i and activity could not be found. [ATP]i and the method and time course of ATP depletion all influenced activity. The inhibition of Na(+)-K(+)-Cl- co-transport, caused by reducing [ATP]i could be partially reversed by restoring [ATP]i to normal. 4. Increasing the concentration of intracellular ionized magnesium [( Mg2+]i) did not stimulate co-transport activity in ATP-depleted cells. This contrasts with the substantial stimulation seen in cells with normal [ATP]i. 5. Vanadate stimulated Na(+)-K(+)-Cl- co-transport activity in ATP-depleted cells but not in cells with normal [ATP]i. Fluoride did not affect activity at any [ATP]i. 6. The effects of some sulphydryl reagents on Na(+)-K(+)-Cl- co-transport were also examined. n-Ethylmaleimide (1 mM) inhibited Na(+)-K(+)-Cl- co-transport while it stimulated bumetanide-resistant potassium transport. Dithiothreitol (1 mM) did not affect activity. Iodoacetamide (6 mM) appeared to reduce the inhibition of cotransport activity seen at low [ATP]i but also greatly increased cell fragility. 7. The data suggest that activity of the Na(+)-K(+)-Cl- co-transport system is controlled by a cycle of phosphorylation and dephosphorylation with the phosphorylated form being active. Phosphorylation and transport appear to be almost maximal in ferret red cells with normal [ATP]i. Reduction of [ATP]i may allow changes in phosphatase activity to manifest as changes in transport rate. Differences in the balance between phosphorylation and dephosphorylation may explain tissue-dependent variations in the response of the system to various stimuli.

Renin release from isolated juxtaglomerular apparatus depends on macula densa chloride transport

Transport inhibitor and ion substitution studies were performed using perfused, superfused preparations of the isolated rabbit juxtaglomerular apparatus to investigate transport dependency of macula densa-mediated renin secretion. In the first experimental series, tubular perfusion with a high-NaCl solution containing 10(-6) M bumetanide increased renin secretion compared with perfusion with high NaCl alone from 8.7 to 24.6 nano-Goldblatt hog units (nGU)/min. Bath addition of 10(-6) M bumetanide had no effect on renin release. The second series tested ability of luminal addition of 54 mmol/l Na or Cl salts to inhibit renin secretion, starting from a stimulated value produced by low-NaCl perfusion. Perfusion with a high-NaCl solution decreased renin secretion from 58.9 to 14.8 nGU/min, which served as a positive control. Addition of choline chloride decreased renin secretion from 42.7 to 16.6 nGU/min, and RbCl decreased renin secretion from 54.9 to 17.0 nGU/min. In contrast, addition of two different Na salts had no effect on renin release (from 41.7 to 31.6 nGU/min with sodium isethionate and from 14.1 to 13.5 nGU/min with sodium acetate). Also, in the presence of 26 mmol/l Cl, addition of 54 mmol/l Na had no effect on renin secretion (29.9-36.8 nGU/min). These data demonstrate that renin secretion is directly stimulated by luminal application of transport blockers and can be inhibited by increases in Cl concentration at the macula densa but not by changes in Na concentration. These results support the hypothesis that the initiating signal for macula densa control of renin secretion is an inverse change in transport rate via the luminal Na(+)-K(+)-2Cl- cotransporter.

Relation between group combustion and drop array studies

Spray combustion modeling requires a knowledge of the strength of the mass and heat sources for each drop in the spray. Since sprays involve a large number of drops, interactive transport processes must be accounted for in estimating the source strengths of the drops. Earlier approaches (called array studies) considered a finite number of drops (2 to 9), and accounted for the three dimensional variation of temperature and species mass fraction profiles in order to determine an evaporation/combustion correction factor. This correction factor is defined as the ratio of the average strength of each drop in the array to the strength of the drop if it is kept in an isolated environment. The current approach utilizes group combustion theory which involves a large number of drops, assumes top hat profiles in the interstitial space between the drops, and accounts for their variation in the radial direction. The correction factor is again determined. This paper reports the results of the current group combustion approach and compares these results with those from array studies when the group combustion approach is extended to an array consisting of as few as 2 to 9 drops. The change in transport rate due to proximity of other drops is accounted for in the present group combustion approach. An unexpected result is the close agreement of the results obtained from group combustion approach with those results from array studies. A simple algebraic expression is given for the correction factor in terms of l a ratio and total number of drops for a 2 to 9 drop array.

Influence of alkali metal cations on the transport of calcium by phosphatidate in multi-phase systems

The effects of alkali metal cations on the rates at which Ca 2+ and phosphatidic acid were cotransported from aqueous to hydrocarbon medium were examined. The alkali metal cations remained in the aqueous phase yet specifically influenced the transport of Ca 2+ into the hydrocarbon solvent. For the physiological cations, Na + and K +, there were critical concentration ranges in which small changes in concentration effected sharp changes in transport rates. The maximal rate observed with Na + was an order of magnitude greater than that with K +; however, unlike Na +, K + promoted low levels of transport below the critical concentration range. Li + effected only low levels of transport even at high concentrations, whereas Rb + and Cs + induced transport at rates proportional to their concentrations. These results are discussed in terms of a classical ionophore model for the complex composed of a neutral phosphatidic acid dimer bridged by Ca 2+.

Adaptation of HCO-3 and NH+4 transport in rat MTAL: effects of chronic metabolic acidosis and Na+ intake

In vitro microperfusion experiments were performed to determine whether chronic metabolic acidosis or chronic alterations in sodium intake cause adaptive changes in bicarbonate or ammonium transport in the medullary thick ascending limb (MTAL) of the rat. In all experiments, MTAL were studied under standard conditions in vitro with 25 mM bicarbonate in perfusate and bath. Thus changes in transport rates reflect adaptive changes in the intrinsic transport properties of the tubule cells. Chronic metabolic acidosis (induced by oral NH4Cl loading) increased MTAL bicarbonate absorption by 53% and increased net ammonium absorption by 36%. Chronic administration of NaHCO3 (0.28 M NaHCO3 drinking H2O) increased MTAL bicarbonate absorption by 50% and increased net ammonium absorption by 54%, despite systemic metabolic alkalosis. Chronic administration of NaCl (0.28 M NaCl drinking H2O) also increased bicarbonate absorption by 50%. Thus an increase in sodium intake stimulated bicarbonate absorptive capacity to a similar extent when sodium was administered with either chloride or bicarbonate. Moderate dietary sodium restriction (0.5% NaCl) reduced bicarbonate absorption by 20% compared with pair-fed sodium-replete controls (2.2% NaCl). These results demonstrate that 1) the MTAL is a site of regulation of renal acid-base transport, 2) chronic metabolic acidosis is associated with adaptive increases in MTAL bicarbonate and ammonium absorption, changes that are appropriate to correct the acidosis, and 3) dietary sodium intake is an important determinant of MTAL bicarbonate and ammonium transport capacity. The response of the MTAL to changes in sodium intake suggests that this segment may play an important role in maintaining acid-base balance when NaCl intake is altered.

Diurnal changes in leaf chemical constituents and (14)C partitioning in cottonwood.

Diurnal changes in concentrations of leaf chemical fractions and partitioning of photosynthetically fixed (14)C within the plant and among chemical fractions were studied in rapidly growing cottonwood (Populus deltoides Bartr. ex Marsh.) seedlings. During the light period, leaf weight (mg cm(-2)) increased by about 25% primarily as a result of the accumulation of starch and sucrose, and to a lesser extent because of an increase in the content of amino acids and the chloroform fraction (pigments plus lipids). In contrast, reducing sugars and organic acids decreased in concentration. The partitioning of (14)C within the plant also changed during the light period. Acropetal transport to developing leaves and stem decreased from 81 to 55% of the total (14)C translocated from a source leaf in 4 hours, whereas basipetal transport to stem and roots increased from 13 to 37%. Although assimilation rate ((14)C fixed in 0.5 h) remained constant during the light period, the percentage of fixed (14)C translocated out of the source leaf in 4 h decreased from 27 to 9%. This change in transport rate of recently fixed (14)C was caused by a shift in (14)C partitioning from transport sucrose to storage starch. During the light period, the incorporation ratio ((14)C-sugar/(14)C-starch) decreased from 40 at 0700 h to 2 at 1900 h. The partitioning of carbon to different chemical fractions within the source leaf and the interactions or feedback between different sinks and the source leaf have a major influence on plant growth and development. Control of this carbon partitioning is located in both source and sink leaves.

A method for measuring apical glucose transporter site density in intact intestinal mucosa by means of phlorizin binding.

Phlorizin binding has been widely used to estimate the site density of glucose transporters on intestinal and renal brush-border vesicles. Glucose transport measurements in the intact intestinal mucosa show that changes in transport rate postulated to arise from changes in site density occur under many physiological and pathological conditions. Exploring the basis of these regulatory phenomena would be facilitated by comparing changes in transport rate and site density measured in the same preparation. Hence we developed methods for measuring phlorizin binding in everted sleeves of intact mouse intestine. Specific binding of phlorizin to glucose carriers reached an asymptotic value within 120 sec, while nonspecific binding continued to rise thereafter. Hence we used 120-sec incubations. The rate of dissociation of specifically bound phlorizin was accelerated by Na+-free solutions and even more by 50 mM glucose, while the rate of dissociation of nonspecifically bound phlorizin was independent of these solution changes. Hence we chose a 20-sec rinse in Ringer + 50 mM mannitol, because it washes out 30-40% of the nonspecifically bound phlorizin but virtually none of the specifically bound phlorizin. Ligand-binding analysis of specific binding against phlorizin concentration suggested two classes of binding sites, of which the one with stronger affinity for phlorizin probably has the higher capacity for glucose transport in mouse jejunum. The calculated affinity and capacity of this component are independent of whether one estimates the specific component of total binding by adding glucose or by removing Na+.

Multiple tracer dilution estimates of D- and 2-deoxy-D-glucose uptake by the heart.

Permeability-surface area products of the capillary wall, PSc, and the myocyte sarcolemma, PSpc, for D-glucose and 2-deoxy-D-glucose were estimated via the multiple indicator-dilution technique in isolated blood-perfused dog and Tyrode-perfused rabbit hearts. Aortic bolus injections contained 131I-albumin (intravascular reference), two of three glucoses: L-glucose (an extracellular reference solute), D-glucose, and 2-deoxy-D-glucose. Outflow dilution curves were sampled for 1-2.5 min without recirculation. The long duration sampling allowed accurate evaluation of PSpc by fitting the dilution curves with a multiregional axially distributed capillary-interstitial fluid-cell model accounting for the heterogeneity of regional flows (measured using microspheres and total heart sectioning). With average blood flow of 1.3 ml . g-1 . min-1, in the dog hearts the PSc for D-glucose was 0.72 +/- 0.17 ml . g-1 . min-1 (mean +/- SD; n = 11), and PSpc was 0.57 +/- 0.15 ml . g-1 . min-1. In the rabbit hearts with perfusate flow of 2.0 ml . g-1 . min-1 (n = 6), PSc was 1.2 +/- 0.1 and PSpc was 0.4 +/- 0.1 ml . g-1 . min-1. PSc for 2-deoxy-D-glucose was about 4% higher than for D-glucose and L-glucose in both preparations. Relative to L-glucose, there was no measurable transendothelial transport of either dextroglucose, indicating that transcapillary transport was by passive diffusion, presumably via the clefts between cells. The technique allows repeated measurements of D-glucose uptake at intervals of a few minutes; it may therefore be used to assess changes in transport rates occurring over intervals of several minutes.

Transport of 2-deoxy- d-glucose by dissociated brain cells

The characteristics of glucose transport into dissociated cells from rat brain were determined using [1,2- 3H]2-deoxyglucose as substrate. The rate of net uptake exhibited biphasic saturation kinetics with increasing substrate concentration; two values each for K m (8.85 and 1.05 mM) and V max (20.41 ± 5.99nmol/min/mg protein) were obtained, indicating the presence of two transport systems. d-glucose competed with [1,2- 3H]2-deoxyglucose as shown by increasing degrees of inhibition of uptake of labeled substrate with increasing concentrations of d-glucose. The presence of an accelerative exchange mechanism was demonstrated by enhanced rates of uptake of labeled substrate by cells pre-loaded with high levels of unlabeled 2-deoxyglucose. Transport was inhibited by cytochalasin B, phloretin and phloridzin in a manner suggesting that the system is sodium-independent. Transport was also inhibited by sodium cyanide, potassium cyanide and dinitrophenol, but not by sodium arsenite or ouabain. Insulin status of the animals had no effect on the rate of transport of this substrate. Net transport was significantly lower in neonatal (4-day-old) rats than in either older sucklings (14–16-day-old) or adult animals; no significant difference between the latter two groups was observed. These findings demonstrate that two carrier-mediated systems for glucose transport are present on the membranes of these mixed brain cells suggesting that the kinetic characteristics of glucose transport may differ between neurons and glial cells. The age change in transport rate may reflect age-associated glial cell proliferation and/or an age-dependent increase in the number of transporters per cell in one brain cell type.

Vaginal Absorption of a Potent Luteinizing Hormone–Releasing Hormone Analogue (Leuprolide) in Rats III: Effect of Estrous Cycle on Vaginal Absorption of Hydrophilic Model Compounds

□ The effect of estrous cycle stages on vaginal absorption was determined by the use of insulin, Phenolsulfonphthalein, and salicylic acid as hydrophilic model compounds. Absorption of these compounds was markedly affected by the stage, possibly due to the change of transport rate through the pore-like pathways. The absorption of Phenolsulfonphthalein during proestrus and estrus is roughly one-tenth of that during metestrus and diestrus. An increase of the nonionized form of salicylic acid, produced by a lowered pH, resulted in an enhancement of absorption during proestrus and diestrus; higher contribution of the transport through the cell membrane possibly reduced an effect of the estrous cycle. However, consecutive daily administration of leuprolide halted the cycle at diestrus and reduced the cycle effect on the vaginal absorption of phenolsulfonphthalein; when the treatment was started at any of the four stages of the cycle, vaginal absorption was enhanced ~20%, with less variance than that observed in normal diestrous rats.

The Polarity of Movement of Endogenously Produced IAA in Relation to a Gravity Perception Mechanism

The polarity of radioactive IAA transport in segments of the leaf sheath base of Avena fatua L. is reversed upon their inversion through 180° transport towards the apex being greater than towards the base. Changes in rates of transport leading to this reversal can be detected within 10–20 min, correlating with the timing of statolith movements from the base to the apex of statocyte cells and conforming to a proposed model for the gravity control of auxin transport. Transport of H3-trytophan-derived H3-IAA was found to undergo similar changes in polarity upon re-orientation as did exogenously applied H3 or C14 IAA. It is concluded that the proposed model also relates to the movement of endogenously produced IAA.

The spontaneously diabetic BB Wistar rat: Morphologic and physiologic studies of peripheral nerve

The spontaneously diabetic “BB” Wistar rat was examined for evidence of peripheral nerve abnormalities by a combined morphologic and physiologic approach. The studies were done on rats kept severely hyperglycemic and frequently ketotic. The peripheral nerves of the lower extremities, including the most distal nerves of the intrinsic foot muscles, revealed only minimal abnormalities by histologic and morphometric examination. Sciatic nerve conduction studies, however, measured over a 2-month period did show a significant slowing in diabetics compared with age-matched controls, as well as between diabetics and weight-matched controls. In addition, fast anterograde axoplasmic transport studies were correlated with serum glucose results. Rats maintained severely hyperglycemic with or without ketosis had abnormal down flow rates of [ 3H]leucine compared to controls. Diabetic rats maintained with normal blood glucose levels showed no change in transport rates. These results suggest that persistent hyperglycemia in the “BB” Wistar rat produces significant physiologic but not significant structural abnormalities in the peripheral nerve.

Hoechst 33342 dye uptake as a probe of membrane permeability changes in mammalian cells.

Flow cytometric analysis of the uptake of the DNA-specific and fluorescent probe Hoechst 33342 (HO342) offers a simple and rapid method for measuring membrane transport rates in mammalian cells and identifying cellular subpopulations that differ in their membrane transport rates. In a Chinese hamster ovary wild-type cell line and in three colchicine-resistant lines derived from it, the rate of uptake of HO342 dye decreases as the stepwise resistance to colchicine increases. A colchicine-sensitive revertant cell line shows an increased rate of dye uptake. Drug resistance in these lines has previously been shown to be related to changes in transport rate. In a manner similar to colchicine, the rate of uptake of HO342 dye shows nonsaturation kinetics. The effects of KCN, a metabolic inhibitor, on HO342 dye uptake, both in the presence and in the absence of glucose, is similar to that previously observed for colchicine uptake. When murine spleen cells are stained with HO342 under appropriate conditions, one sees two populations of lymphocytes differing in HO342 fluorescence intensity, a difference not related to DNA content. The two subpopulations show the same relative difference in both colchicine and HO342 uptake. HO342 dye appears, therefore, to enter mammalian cells by the same mechanism as colchicine--i.e., by unmediated diffusion--and can be used as a probe of cytoplasmic membrane permeability. Potential applications of the dye in studies of drug resistance, detection of activated T cells, and recognition of lymphocyte subpopulations are discussed.

Influence of ( dl)-propranolol and Ca 2+ on membrane potential and amino acid transport in Ehrlich ascites tumor cells

1. (1) ( dl)-Propanolol and Ca 2+ are shown to alter the transmembrane potential difference of Ehrlich ascites tumor cells as measured by means of the cyanine dye, 3,3′-dipropyl-2,2′-thiodicarbocyanine iodide, whose fluorescent intensity changes as a function of membrane potential. 2. (2) The changes in membrane potential elicited by these agents are dependent on the external K + concentration in a manner which suggests that the potential changes result from a specific increase in the permeability of the plasma membrane to K +. 3. (3) Na +-dependent amino acid transport in the presence of propranolol can be modulated by varying the external K + concentration (K o +). The initial rate of uptake is stimulated by propranolol at low K o + and inhibited at high K o +. The change in transport rate is nearly directly proportional to the natural logarithm of [K +] o in the presence of propranolol. 4. (4) ATP depletion of the cells by preincubation with rotenone abolishes the changes in fluorescence and amino acid uptake seen with propranolol as a function of K o +. Restoration of cellular ATP with glucose in presence of Ca 2+ restores both fluorescence and amino acid transport changes which occur in response to propranolol. 5. (5) The fluorescence changes and amino acid transport changes in response to propranolol are pH dependent, with little effect seen at pH 6. 6. (6) It is concluded that the rate of Na +-dependent amino acid uptake is a function of membrane potential and is dependent on the electrochemical potential difference for Na +.