scholarly journals Hans Henriksen Ussing. 30 December 1911 — 22 December 2000

2009 ◽  
Vol 55 ◽  
pp. 305-335 ◽  
Author(s):  
Erik Hviid Larsen

Hans Ussing was born on 30 December 1911 at Sorø Academy in Denmark, where his father Dr Henrik Ussing was a lecturer and, as historian, a leading Danish folklorist. After his doctoral thesis in marine biology, Hans Ussing came to August Krogh's laboratory, where he studied protein turnover by using deuterium-labelled amino acids. After World War II, when radioactive isotopes of light elements became available for biological research, Ussing pioneered the development of epithelial physiology by introducing new concepts and theoretical tools, such as unidirectional fluxes, exchange diffusion, the flux-ratio equation, the shortcircuiting technique, solvent drag, anomalous solvent drag and the pre-steady-state flux ratio theorem. In studies on frog skin, combining electrophysiology and radioactive tracer technology, he provided the first unambiguous demonstration of active transport of sodium ions. His two-membrane hypothesis of active transport by frog skin initiated studies of epithelial transport at the cellular level in other organs and of the mechanisms of action of hormones and drugs. His discovery of paracellular ion transports bridged the physiology of high-resistance and low-resistance epithelia. With the Na + recirculation theory of isotonic transport he continued his studies of epithelial physiology until shortly before his death. Ussing's scientific research provided analytical methods and new insights of general applicability for the study of absorbing and secreting epithelia—of equal importance to biology and medicine. Hans Ussing died on 22 December 2000 after a short illness.

1975 ◽  
Vol 65 (5) ◽  
pp. 599-615 ◽  
Author(s):  
L J Mandel

Increases in transepithelial solute permeability were elicited in the frog skin with external hypertonic urea, theophylline, and vasopressin (ADH). In external hypertonic urea, which is known to increase the permeability of the extracellular (paracellular) pathway, the unidirectional transepithelial fluxes of Na (passive), K, Cl, and urea increased substantially while preserving a linear relationship to each other. The same linear relationship was also observed for the passive Na and urea fluxes in regular Ringer and under stimulation with ADH or 10 mM theophylline, indicating that their permeation pathway was extracellular. A linear relationship between Cl and urea fluxes could be demonstrated if the skins were separated according to their open circuit potentials; parallel lines were obtained with increasing intercepts on the Cl axis as the open circuit potential decreased. The slopes of the Cl vs. urea lines were not different from that obtained in external hypertonic urea, indicating that this relationship described the extracellular movement of Cl. The intercept on the ordinate was interpreted as the contribution from the transcellular Cl movement. In the presence of 0.5 mM theophylline or 10 mU/ml of ADH, mainly the transcellular movement of Cl increased, whereas 10 mM theophylline caused increases in both transcellular and extracellular Cl fluxes. These and other data were interpreted in terms of a possible intracellular control of the theophylline-induced increase in extracellular fluxes. The changes in passive solute permeability were shown to be independent of active transport. The responses of the active transport system, the transcellular and paracellular pathways to theophylline and ADH could be explained in terms of the different resulting concentrations of cyclic 3'-5'-AMP produced by each of these substances in the tissue.


1977 ◽  
Vol 232 (6) ◽  
pp. F550-F558
Author(s):  
C. O. Watlington ◽  
S. D. Jessee ◽  
G. Baldwin

Two distinctly different mechanisms for active Cl- transport in epithelia may exist: one, ouabain-sensitive and cation-dependent, and the other, acetazolamide-sensitive and cation-independent. As a test of this hypothesis the three active Cl- transport systems in isolated short-circuited skin of Rana pipiens were examined. Sensitivity to ouabain (10(-4) M) and acetazolamide (5 X 10(-3) M) and dependence on Na+ and K+ in the medium were ascertained. The first system, net chloride influx in ordinary Ringer, exhibited specific ouabain sensitivity and acetazolamide insensitivity. As we have previously shown this system to be clearly dependent on Na+ on the cis and K+ on the trans side, cation dependence was not re-studied. The second system, isoproterenol-stimulated net Cl- outflux, was also ouabain-sensitive and acetazolamide-insensitive. It was dependent on the presence of Na+ on the cis side, but the K+ dependence was less clear. In contrast to the first two, the third system (net influx in low Cl- medium sulfate Ringer containing 2.4 mM Cl-) was largely ouabain-insensitive, completely acetazolamide-sensitive and independent of both Na+ and K+. Thus, the hypothesis of two distinct mechanisms seems to hold for the three active Cl- transport systems in frog skin. Data from various other Cl- transporting epithelia are examined, and the general applicability of such a scheme of categorization for active Cl- transport mechanisms is discussed.


1966 ◽  
Vol 67 (3) ◽  
pp. 367-373 ◽  
Author(s):  
Duncan W. Martin ◽  
Peter F. Curran
Keyword(s):  

1983 ◽  
Vol 218 (1212) ◽  
pp. 309-329 ◽  

A set of experiments was simulated on a computer version of the Koefoed-Johnsen & Ussing model for high-resistance epithelia. The results obtained were analysed according to procedures commonly applied to the analyses of experimental data and interpreted in terms of the model parameters. Although the computer model encodes a stoichiometry of 3:2 for Na-K exchange through the Na pump, the simulation of published experimental procedures yields different figures in almost every case. We show that E Na as originally defined by Ussing & Zerahn ( Acta physiol. scand . 23, 110-127 (1951)) and as obtained from flux-ratio experiments has different values under different experimental conditions with unchanged system parameters and that it is distinct from E Na measured by other methods. We also show that unless the pump is saturated with internal Na an increase in the rate of pumping cannot cause a substantial increase in the rate of transepithelial Na transport.


1982 ◽  
Vol 243 (6) ◽  
pp. F581-F587 ◽  
Author(s):  
A. Corcia ◽  
S. R. Caplan

When added to the mucosal solution bathing isolated frog skin at concentrations ranging from 5 X 10(-4) to 3 X 10(-3) M, the diuretic furosemide increased both the active transport of sodium and the electrical potential difference across the tissue in a dose-dependent way. The same effect was observed in chloride-free solutions. Mucosal furosemide also decreased the passive unidirectional fluxes of chloride. We believe that as far as electrical parameters are concerned mucosal furosemide has a double effect in frog skin: it increases the active conductance to sodium across the mucosal membrane, thus increasing active transport, and decreases the passive permeability to chloride, thus altering the passive conductance of the skin. The relative increase in short-circuit current was, however, invariably greater than the increase of the active conductance, suggesting the influence of yet a third effect. The effect of mucosal furosemide on active sodium transport was blocked by amiloride (5 X 1-(-5) M) and was independent of vasopressin. Qualitatively the effect was similar to the effect produced by triphenylmethylphosphonium ion.


1977 ◽  
Vol 232 (1) ◽  
pp. 67-75 ◽  
Author(s):  
T. U. Biber ◽  
T. L. Mullen

The transepithelial efflux of Na and several nonelectrolytes (mannitol, sucrose, and polyethylene glycol 900) were measured in the isolated frog skin under short-circuited conditions in chambers that had been specially designed to avoid edge damage. Ouabain (10(-3) and 10(-4) M) caused a dramatic increase in the efflux of Na, whereas the efflux of nonelectrolytes showed only a slight alteration. The efflux of Na increased after the application of dinitrophenol (10(-4) M), whereas the efflux of nonelectrolytes remained constant. Amiloride (10(-3) M) caused large variations in the efflux of Na, whereas the efflux of nonelectrolytes remained unchanged. The results provide evidence that these inhibitors do not alter the permeability of the paracellular pathway and that the total transepithelial efflux of Na or at least a very large portion of it, and possibly also the transepithelial efflux of Cl, proceeds via a transcellular pathway and not a paracellular pathway as has been widely accepted. The data further suggest that the Na proceeding via this pathway interacts directly or indirectly with the active transport step.


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