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A Essig

Publications and source records attributed to A Essig.

At least 73 records · Page 4Linked to original sources

Thermodynamic analysis of active sodium transport and oxidative metabolism in toad urinary bladder.

Measurements of electrical current and oxygen consumption were carried out concurrently under voltage clamp conditions in 11 toad hemibladders. Inhibition of active transport with amiloride then permitted evaluation of the passive conductance and the rate of basal oxygen consumption Jbr, allowing the simultaneous determination of the rates of active sodium transport JaNa and suprabasal oxygen consumption Jsbr-JaNa and Jabr were linear functions of the electrical potential difference over a range of +/- 80 mV. This allowed the comprehensive application of a linear nonequilibrium thermodynamic formalism, leading to the evaluation of the affinity A (negative free energy) of the metabolic reaction driving transport, all phenomenological coefficients, and the degree of coupling q relating transport to metabolism. Values of A determined by two techniques were A1=56.0 +/- 5.8 and A2=58.2 +/- 6.5 kcal per mole. Values of q determined by two techniques agreed well and were less than 1, indicating incompleteness of coupling, and hence lack of fixed stoichiometry between Na transort and O2 consumption. The affinity and the electromotive force of sodium transport ENa are not closely correlated, reflecting the fact that ENa comprises both kinetic and energetic factors.

Animals↗

Sodium transport and oxygen consumption in toad bladder. A thermodynamic approach.

The relationship between active sodium transport and oxygen consumption was investigated in toad urinary bladder exposed to identical sodium-Ringer's solution at each surface, while controlling the transepithelial electrical potential difference delta phi. Rates of sodium transport and oxygen consumption were measured simultaneously, both in the short-circuited state (delta phi = 0) and when delta phi was varied. Under short-circuit conditions, when the rates of active sodium transport changed spontaneously or were depressed with amiloride, the ratio of active sodium transport to the estimated suprabasal oxygen consumption Na/O2 was constant for each tissue, but varied among different tissues. Only when delta phi was varied did the ratio Na+/O2 change with the rate of active sodium transport; under these circumstances dNa+/dO2 was constant but exceeded the ratio measured at short-circuit [(Na+/O2)delta phi = 0[. This suggests that coupling between transport and metabolism is incomplete. The results are analyzed according to the principles of nonequilibrium thermodynamics, and intepreted in terms of a simple model of the transepithelial sodium transport system.

Animals↗

Influence of membrane heterogeneity on kinetics of nonelectrolyte tracer flows.

In a composite membrane with heterogeneous channels, prevention of net volume flow with hydrostatic pressure differences and/or impermeant osmotic solutes may induce positive isotope interaction (coupling of isotope flows) consequent to circulation of volume flow. The permeability coefficient for net flow will then exceen the tracer permeability coefficient. A permeant osmotic solute will induce either positive or negative isotope interaction, according to whether membrane heterogeneity is more marked for the test solute or the osmotic solute, respectively. Thus membrane heterogeneity may account for phenomena commonly attributed to "single file diffusion". For sufficiently small flows the general flux ratio relationship for homogeneous membranes will continue to apply.

Biological Transport↗

The thermodynamic degree of coupling between metabolism and sodium transport in frog skin.

The tightness of coupling between two processes is advantageously evaluated by the thermodynamic degree of coupling q, varying in absolute value from zero for uncoupled processes to unity for processes which are related stoichiometrically. Two methods for the determination of q in the active pathway in frog skin have been developed, employing amiloride to abolish active sodium transport. The values of q in 6 frog skins varied, but were always less than unity (mean 0.79 +/- 0.06 S.E. according to one method, 0.78 +/- 0.06 S.E. according to the other). This indicates that metabolism and sodium transport are incompletely coupled in this tissue even when passive transepithelial leakage pathways are taken into account.

Amiloride↗

Effects of 2-deoxy-D-glucose, amiloride, vasopressin, and ouabain on active conductance and ENa in the toad bladder.

The effects of various agents on active sodium transport were studied in the toad bladder in terms of the equivalent circuit comprising an active conductance Ka, an electromotive force ENa, and a parallel passive conductance Kp. For agents which affect Ka, but not ENa or Kp, the inverse slope of the plot of total conductance K against short-circuit current IO evaluates ENa, and the intercept represents Kp. Studies employing 5 X 10(-7) M amiloride to depress Ka indicate a changing ENa, invalidating the use of the slope technique with this agent. An alternative suitable technique employs 10(-5) M amiloride, which reduces IO reversibly to near zero without effect on Kp. Despite curvilinearity of the K-IO plot under these conditions, Kp may therefore be estimated fairly precisely from the residual conductance. It then becomes possible to follow the dynamic behavior of Ka and ENa (in the absence of 10(-5) M amiloride) by frequent measurements of K and IO, utilizing the relationships Ka=K-Kp, and ENa=IO/(K-Kp). 2-deoxy-D-glucose (7.5 X 10(-3)M) depressed both Ka and ENa. All of the above effects were noted promptly; Kp was unaffected. The "electromotive force of Na transport" ENa appears not to be a pure energetic parameter, but to relfect kinetic factors as well, in accordance with thermodynamic considerations.

Amiloride↗

Action of aldosterone on frog skin in the presence and absence of in vitro molting effects.

The molting which occurs in frog skin following exposure to high concentrations of aldosterone interferes with the interpretation of physiological measurements. Exposure of skins from frogs maintained in standard smooth tanks to 5 - 10(-7) M aldosterone caused within a few hours erratic responses in short-circuit current Io and conductance K followed by sustained stimulation of Io and K; 10(-8) M aldosterone caused only stimulation of Io and K. Storage of frogs in "rojgh tanks" eliminated in vitro molting on exposure to 5 - 10(-7) M aldosterone. IO and K were then superimposable for 3 h, after which Io increased far more rapidly than K. These results are consistent with an early effect on permeability of the active pathway and later effects on metabolism, either a direct effect on the pump or enhanced interaction between transport and metabolism.

Aldosterone↗

A comparison of the effects of ouabain and 2-deoxy-D-glucose on the thermodynamic variables of the frog skin.

Previous studies support the validity of a linear thermodynamic formalism relating the rates of active Na-+ transport and oxygen consumption Jr to the electrical potential difference delta-psi and the affinity A (negative free energy) of the metabolic driving reaction. The formulation was further tested in paired control and experimental hemiskins by the use of two inhibitors of Na-+ transport. Ouabain, a specific inhibitor of the Na-+ pump, might be expected to diminish the dependence of Jr on delta-psi without affecting A, whereas 2-deoxy-D-glucose, a competitive inhibitor of glucose metabolism should be expected to diminish A. Both inhibitors were used at concentrations adequate to depress Na-+ transport (i.e. short-circuit current Io) to some 50% of control level. Measurements were made of Io and dJr/d(delat-psi), and the apparent value of the affinity Aapp was calculated according to the thermodynamic formulation. Ouabain depressed minus dJr/d(delta-psi) without affecting Aapp whereas 2-deoxy-D-glucose depressed Aapp without affecting minus dJr/d(delta-psi). The demonstration of these effects indicated the utility of the formalism.

Animals↗

Tracer flow, permeability, and partial conductance.

It is often not possible to evaluate a permeability coefficient for net flow P from the small flows produced by physiological gradients of concentration or electrical potential. The common use of a tracer permeability coefficient P-x for this purpose, under the assumption that P-x = P, requires that the species be transported passively, and that there be no significant coupling between its flow and that of other chemical species, and between the flows of its tracer and abundant isotopes (isotope interaction). These conditions are often not satisfied. However, for passive transport in the absence of coupling of flows of different chemical species the measurement of tracer flow at two values of electrical potential difference evaluates (P-x/P) and thus P. In the presence of coupling of flows of different chemical species, although these measurements no longer evaluate P, they evaluate the partial conductance G. A graphical method of evaluating (p-x/P), P, and G is presented.

Animals↗

Energetics of active transport processes.

Active sodium transport across epithelial membranes has been analyzed by means of linear nonequilibirium thermodynamics. In this formulation the rates of active sodium transport JNa and the associated metabolic reaction Jr are postulated to be linear functions of both the electrochemical potential difference of sodium--XNa and the affinity A (negative free energy) of the metabolic reaction of driving transport. Experimental studies in various epithelia demonstrate that both JNa and Jr (oxygen consumption) are indeed linear functions of XNa. Theoretical considerations and experimental studies in other systems suggest that likelihood of linearity in A as well. If so, A may be evaluated. Several observations indicate that the quantity A evaluated from the thermodynamic formalism does in fact reflect the substrate-product ratio of the metabolic reaction which supports transport. This is in contrast to measurements of mean cellular concentrations, which may not reflect conditions at the site of transport. Associated studies of isotope kinetics permit the distinction between effects on the permeability of the active and passive transport pathways. With these combined approaches, it may prove possible to characterize both the energetic and permeability factors which regulate transport. The formulation has been applied to an analysis of the mechanism of action of the hormone aldosterone.

Aldosterone↗