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Biomedical subjects

S R Caplan

Publications and source records attributed to S R Caplan.

At least 91 records · Page 5Linked to original sources

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↗

Energetics of sodium transport in frog skin. I. Oxygen consumption in the short-circuited state.

Sodium transport and oxygen consumption were studied simultaneously in the short-circuited frog skin. Sodium transport was evaluated from I(o)/F, where I(o) is the short-circuit current measured with standard Ringer's solution bathing each surface and F is the Faraday constant. Oxygen tension was measured polarographically. Under a variety of circumstances the rate of oxygen consumption from the outer solution exceeded that from the inner solution, the ratio being constant (0.57 +/- 0.09 SD). Both I(o) and the associated rate of oxygen consumption J(ro) declined nonlinearly with time, but the relationship between them was linear, suggesting that the basal oxygen consumption was constant. For each skin numerous experimental points were fitted by the best straight line. The intercept (J(ro))(Io=0) then gave the basal oxygen consumption, and the slope dNa/dO(2) gave an apparent stoichiometric ratio for a given skin. The basal oxygen consumption was about one-half the total oxygen consumption in a representative untreated short-circuited skin. Values of dNa/dO(2) in 10 skins varied significantly, ranging from 7.1 to 30.9 (as compared with Zerahn's and Leaf and Renshaw's values of about 18). KCN abolished both I(o) and J(ro). 2,4-dinitrophenol (DNP) depressed I(o) while increasing J(ro) four- to fivefold. Anti-diuretic hormone stimulated and ouabain depressed both I(o) and J(ro); in both cases apparent stoichiometric ratios were preserved.

Animals↗

Energetics of sodium transport in frog skin. II. The effects of electrical potential on oxygen consumption.

Studies were made of the dependence of the rate of oxygen consumption, J(r), on the electrical potential difference, Deltapsi, across the frog skin. After the abolition of sodium transport by ouabain the basal oxygen consumption was independent of Deltapsi. In fresh skins J(r) was a linear function of Deltapsi over a range of at least +/-70 mv. Treatment with aldosterone stimulated the short-circuit current, I(o), and the associated rate of oxygen consumption, J(ro), and increased their stability; linearity was then demonstrable over a range of +/-160 mv. Brief perturbations of Deltapsi (+/-30-200 mv) did not alter subsequent values of I(o). Perturbations for 10 min or more produced a "memory" effect both with and without aldosterone: accelerating sodium transport by negative clamping lowered the subsequent value of I(o); positive clamping induced the opposite effect. Changes in J(ro) were more readily detectable in the presence of aldosterone; these were in the same direction as the changes in I(o). The linearity of J(r) in Deltapsi indicates the validity of analysis in terms of linear nonequilibrium thermodynamics-brief perturbations of Deltapsi appear to produce no significant effect on either the phenomenological coefficients or the free energy of the metabolic driving reaction. Hence it is possible to evaluate this free energy.

Aldosterone↗

Charge-mosaic membranes: dialytic separation of electrolytes from nonelectrolytes and amino acids.

Charge-mosaic membranes were used for dialytic separations of potassium chloride from low-molecular-weight nonelectrolytes and neutral amino acids. The permeability ratio (potassium chloride to uncharged species) ranged from about 6 in the case of methanol to about 86 in that of mannitol. A theoretical model predicts that optimum rates of dialysis should be achieved by dialyzing against salt concentrations other than zero; this prediction was confirmed by experiment. These observations suggest potential applications of mosaics in laboratory separations, industrial processing, and hemodialysis.

Dialysis↗

Oxidative phosphorylation: thermodynamic criteria for the chemical and chemiosmotic hypotheses.

Oxidative phosphorylation is analyzed by means of nonequilibrium thermodynamics. It is shown that a mitochondrial system may be characterized in terms of the externally fixed affinities (negative free energies) for oxidation and phosphorylation A(o) (ex) and A(p) (ex), without knowledge of internal activities. If the electrochemical potential difference of H(+) is also fixed, a decision can be made between the chemiosmotic and chemical hypotheses. The chemiosmotic hypothesis is shown to be a limiting case of the chemical hypothesis. In general the P/O ratio cannot be expected to be constant, but will vary with A(p) (ex)/A(o) (ex); for certain ranges the variation may be marked.

Binding Sites↗

Charge-mosaic membranes: enhanced permeability and negative osmosis with a symmetrical salt.

Charge-mosaic membranes are prepared by embedding a single layer of alternating cation and anion exchange beads in silicone resin. Membranes made in an identical manner but containing only one type of exchanger serve as controls. The mosaic membranes are 50 to 100 times more permeable to potassium chloride than the controls; and furthermore they give rise to net volume flow from concentrated to dilute solutions of potassium chloride in the absence of a pressure gradient ("negative osmosis"), whereas the controls exhibit normal osmotic behavior. The negative reflection coefficients of the mosaics suggest potential applications in desalination.

Ion Exchange↗

Autonomic energy conversion. I. The input relation: phenomenological and mechanistic considerations.

The differences between completely and incompletely coupled linear energy converters are discussed using suitable electrochemical cells as examples. The output relation for the canonically simplest class of self-regulated incompletely coupled linear energy converters has been shown to be identical to the Hill force-velocity characteristic for muscle. The corresponding input relation (the "inverse" Hill equation) is now derived by two independent methods. The first method is a direct transformation of the output relation through the phenomenological equations of the converter; Onsager symmetry has no influence on the result. The second method makes use of a model system, a hydroelectric device with a regulator mechanism which depends only on the operational limits of the converter (an electro-osmosis cell operated in reverse) and on the load. The inverse Hill equation is shown to be the simplest solution of the regulator equation. An interesting and testable series of relations between input and output parameters arises from the two forms of the Hill equation. For optimal regulation the input should not be greatly different in the two limiting stationary states (level flow and static head). The output power will then be nearly maximal over a considerable range of load resistance, peak output being obtained at close to peak efficiency.

Autonomic Nervous System↗