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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    The journal of membrane biology 15 (1974), S. 87-106 
    ISSN: 1432-1424
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Summary The multicompartmental frog skin epidermis model proposed in a previous paper was applied to computer simulation studies on the kinetics of the wash-out process of Na* from frog skin. Both the kinetics of loading of the model membrane with Na* from the outside to reach steady-state conditions in all internal compartments, and of the wash-out process were followed. This was done for the case when two Na+ pumps were operative, or inoperative, simulating the inhibitory effect of ouabain on active Na+ transport in frog skin. The two pumps were characterized as transmembrane Na+ flow pumps, and internal Na+ maintenance pumps which contribute but little to net inward Na+ flux. The simulation results were in good agreement, both qualitatively and quantitatively, with data in the literature on the behavior of frog skin epidermis. This analysis gives support especially to the views held by Zerahn on location and size of the active Na+ transport pool in skin epithelium. Beyond this, however, this study clearly delineates the experimental conditions under which the estimation of the Na+ transport pool by the method of measuring the wash-out rate of Na* may be successful, and under which conditions this method will fail.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    The journal of membrane biology 15 (1974), S. 47-66 
    ISSN: 1432-1424
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Summary The operation of a seven-compartment model is described with respect to flows of Na+ within and across this system, simulating published results obtained on frog skin. The seven compartments represent: one outside and one inside solution compartment; the subcorneal space; the first reacting cell layer (1. RCL); the remaining cell compartment; the non-, or slowly exchangeable Na+ compartment; the extracellular space. Assuming reasonable volumes for the epidermal compartments and further chosing, by trial and error, appropriate rate constants, a set of seven simultaneous linear differential equations was solved by the application of the Continuous System Modeling Program (CSMP), using an IBM 1130 computer. Initial conditions for influx, backflux and net flux were taken which correspond to [Na+]0; [Na+] i =115mm. Print-out data were obtained at 0.5-min intervals for 30 min, when steady states were obtained in 13 models studied, varying certaink's thus simulating actions of chemical agents (hormones; drugs). Simulation was achieved with regard to rate of influx, backflux and net flux, steady-state time (30 min), and electrical potentials. In addition, this approach gave detailed information on Na+ pool sizes and their variations with changes ink's. These results are compared to published data on frog skin and good agreement between operation of skin epidermis and model was found.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    The journal of membrane biology 15 (1974), S. 67-86 
    ISSN: 1432-1424
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Summary The operation of the multicompartmental frog skin epidermal model 10E described in the preceding paper was tested to find out by computer simulation whether it responds to changes in [Na+] in the same manner as frog skin. In the range from 5 to 115mm [Na+]0, the rate of net Na+ flux across skin is known to increase. The results can be fitted to Michaelis-Menten's law of reaction kinetics, or, alternately, to Hoshiko's linear function, plotting fluxvs. log [Na+]0. Model 10E simulated the laboratory results on skin, provided that the rate coefficients at the site of entry of Na+ into the system were varied in exactly the same manner as they actually were found to vary in skin. In model studies, Na+ backflux (outflux) decreased with increasing [Na+]0, contrary to observations on skin. This discrepancy may be related to adaptive reactions in skins (decrease in permeability) when [Na+]0 is lowered, a feature that has not been modeled. It is known that the skin p.d. changes, mostly, by approximately 35 mV per decade change in [Na+]0. Model 10E gave very nearly the same result when the rate coefficients for entry of Na+ were changed as mentioned above (i.e., varied exactly as they were found to vary in skin). Skin and model 10E behaved similarly in that, at [Na+]0=[Na+] i =115mm, the extent to which labeling with Na* from the outside (12%) and from the inside (88%) is possible was the same. Model data are presented which show in which way the Na+ pools, [Na+] in the individual compartments, and intercompartmental fluxes changed with changing [Na+]0. Because of lack of experimental data on skin for comparison, these calculated results are purely hypothetical, but they are not unreasonable.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1615-6102
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary An apparatus for the automatic recording of the bioelectric potential of isolated frog skin and of the “short-circuit current,” which is a measure of “active” Na+ transport, is described. The equivalence of the uninterrupted short-circuit current and active Na+ transport has been checked. Current and Na+ transport agreed within 2%. The automatic ion transport recorder is particularly suited in studies where the exact time course of the effects of enzyme inhibitors, drugs and other chemicals on skin is of interest. This is illustrated by showing the effects of fluoroacetate, quinone and hydroquinone on spontaneous skin potential and short-circuit current. Attention is called to characteristic transients in the potential records which are probably related to changes in skin permeability to passively moving chloride ions.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Pflügers Archiv 385 (1980), S. 243-251 
    ISSN: 1432-2013
    Keywords: Frog skin ; Amiloride ; Sodium transport ; Distribution of sodium ; Computer simulation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Previous studies have shown that the flow of Na+ in a multicompartment, dual Na+ pump frog skin model is in all hitherto tested kinetic and thermodynamic properties consistent with observations made on skin. It is shown here, that this is also true for a simulated amiloride block by which entrance of Na+ into a “transport compartment” via two parallel pathways is stopped. By the method of computer simulation, the following results were obtained.Before amiloride, steady state transmembrane influx (nEq×cm−2×min−1)J i=21. EffluxJ e=0.5 in a “tight” model, and 3.9 in a model which is “leaky” in its paracellular pathway. Total epidermal Na+ pool (under net flux conditions (nEq/cm2)P n=330, or 160 in a model with a stronger “Na+ maintenance pump”. The steady state time was nearly 1 h.After amiloride, rapid decrease of uptake of Na+ from the outside, slower release of Na+ to the inside under influx conditions; half time (min)t h=2.2 ifP n=330; 0.9 ifP n=160. A new steady state was reached in 12–15 min.J e decreased by 45% in the tight model. In the leaky model,J e increased by 3%. Loss of Na+ from the model under net flux conditions, ΔP n=30 nEq/cm2 ifP n=330, δP n=16 ifP n=160. The kinetic analysis suggests new laboratory experiments, and detailed layouts of speculative, but plausible Na+ current fields. These include for all compartments, values for [Na+]varying from 21 (P n=160) to 63 (P n=330) mM. In the Na+ transport compartment, [Na+] decreased from 5.5 to 1.4 mM after the simulated amiloride block.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Pflügers Archiv 394 (1982), S. 130-138 
    ISSN: 1432-2013
    Keywords: Frog skin ; Ouabain ; Short-circuit current ; Na+ transport ; Na+ pools ; Computer simulation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Among 48 pieces of paired frog skins ofRana pipiens in Ringer's solution, 10 pieces showed a strictly monotone decrease in the short circuit current (SCC) following ouabain treatment (10−4 M). In 9 cases a transient attenuation, and in 27 cases a distinct wave in the ebb of the SCC, was seen. In 2 instances, two waves were seen. Associated with the not-monotone events was a transient rise in electrical skin conductance. The reasons for these mixed skin responses are unknown. One possible reason is considered here: Early during the ouabain action, some of the Na+ entering from the mucosal side is trapped in the skin by electroneutral processes, in keeping with the already known fact that ultimately cellular KCl is partly replaced by NaCl. Computer assisted model studies show how monotone, and not-monotone “transepithelial” net Na+ flux curves can be generated. Essential conditions for the generation of notmonotone Na+ flux curves are: 1. Presence of two distinct “cellular”, active Na+ pools in the model. 2. Presence of a loop pathway in which a principal “transepithelial Na+ transport compartment”, and a constitutent “Na+/K+ maintenance compartment”, are connected to each other and to the “extracellular” compartment. The model, then, predicts under which kinetic conditions monotone and not-monotone transepithelial Na+ flux curves will be seen.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Pflügers Archiv 255 (1952), S. 16-26 
    ISSN: 1432-2013
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Annals of biomedical engineering 5 (1977), S. 194-207 
    ISSN: 1573-9686
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Technology
    Notes: Abstract In this study we have applied a multicompartment whole frog skin model to a kinetic analysis of the process of washout of radioactive sodium (Na*) from both the epidermis and the underlying corium (dermis). This work is different from earlier publications from this laboratory in which only epidermis was considered. The whole skin model is designed in accordance with presently known anatomical and physiological information on frog skin. The chief aim of this analysis of well-known kinetic laboratory data was to present numerical computer data suggesting that the slow Na* washout component (t 1/2≅15 min) seen in laboratory studies, results from the participation of cellular (glandular) structures in the corium, not those in the epidermis. In addition, computed data on [Na+] profiles in the model membrane are briefly presented. Although the [Na+] values appear intuitively reasonable, they await experimental confirmation, which requires an analytical technique with a resolution power far superior over that of conventional histochemical methods. The [Na+] gradients are, however, compatible with the known total Na+ content of skin and the overall input-output flows of Na+ across frog skin.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Annals of biomedical engineering 7 (1979), S. 73-94 
    ISSN: 1573-9686
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Technology
    Notes: Abstract Epithelial membranes are multicompartment structures of microscopic and submicroscopic dimensions. Therefore, interpretations of kinetic data on solute fluxes, based on the standard three compartment model are open to criticism. We have obtained an integrated view of the kinetics of Na+ transport in frog skin epidermis by application of the computer simulation method. Epidermis and whole skin models were designed which resemble photomicrographs of these tissues. Justification is given for the way in which internal and external chamber compartments are connected (topology). The epidermis model has eight passive, and two active transfer sites. Our primary aims were 1) simulation of the transepidermal Na+ influx and the concomitant Na+ backflux saturation kinetics, and 2) localization of the so-called “outer” and “inner” Na+ responsive borders in epidermis. The analysis, based on methodical variations of transfer coefficients, suggests involvement of the “composite desmosomes” and the transepithelial Na+-pump leak pathway. These are located in the outer and the inner region of the epidermis, respectively. Reasonable functional agreement between epidermis and model was also seen in 1) Na+ saturation kinetics in ouabain, poisoned system, 2) relative independence of the two borders to the “trans” [Na+] in the external solutions, and 3) equal energy requirement, for the transmembrane Na+ pump, Na+/O2∼-20.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Annals of biomedical engineering 7 (1979), S. 202-202 
    ISSN: 1573-9686
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Technology
    Type of Medium: Electronic Resource
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