bluuebunny/crossref_metadata_2025 huggingface dataset:
On the Molecular Characterization of the Sodium-Potassium Transport Adenosine Triphosphatase
Authors: Hokin Lowell E.
Published: May 2004

The phosphorylated intermediate in the (Na + K)-activated adenosine triphosphatase (Na-K ATPase) has been characterized as an L-glutamyl-γ-phosphate residue in the enzyme. This has been accomplished by digestion of the phosphorylated and nonphosphorylated forms of the enzyme with pepsin, reaction of the pepsin digests with [2,3-3H]N-(n-propyl)hydroxylmine, further digestion of the derivatized peptides with pronase in the presence of carrier L-glutamyl-γ-N-(n-propyl)hydroxamate and carrier L-aspartyl-N-(n-propyl)hydroxamate, and chromatographic purification. An increment in radioactivity migrated with authentic L-glutamyl-γ-N-(n-propyl)hydroxamate in a total of seven electrophoretic and chromatographic systems and on gel filtration. No increment in radioactivity was associated with authentic L-aspartyl-ß-N-(n-propyl)hydroxamate in five out of the seven chromatographic and electrophoretic systems. At the last stage of purification the radioactivity from the phosphorylated enzyme which migrated as L-glutamyl-γ-N-(n-propyl)hydroxamate was 2½ times that from the nonphosphorylated enzyme. On the basis of these results it is concluded that the phosphorylated intermediate in the Na-K ATPase is an L-glutamyl-γ-phosphate residue. The beef brain Na-K ATPase has been solubilized with the nonionic detergent, Lubrol, and has been purified 10 times over that in the original microsomes. The soluble enzyme remains stable in the presence of ATP and either Na+ or K+. If the partially purified enzyme is electrophoresed in 3% polyacrylamide, followed by incubation with ATP, Na+, K+, and Mg++, a single, somewhat diffuse, ATPase band, which is ouabain-sensitive is seen. Protein impurities are also seen on the gel. Gel electrophoresis, after treatment of the partially purified enzyme with phenol-acetic acid-urea, shows about 12 discrete protein bands. Studies on the site-directed alkylation of the (Na + K)-activated adenosine triphosphatase with haloacetate derivatives of cardiotonic steroids are reviewed. Efforts are now underway to specifically alkylate the cardiotonic steroid site of the Na-K ATPase with hellebrigenin 3-[2-3H]iodoacetate and to purify the subunit of the enzyme containing the cardiotonic steroid site by following radioactivity. Finally, a working model for the role of the Na-K ATPase in the coupled transport of Na and K is presented.
Resolution and Reconstitution of a Mammalian Membrane
Authors: Racker Efraim
Published: May 2004

The problem of the resolution and reconstitution of the inner mitochondrial membrane has been approached at three levels. (1) Starting with phosphorylating submitochondrial particles, a "resolution from without" can be achieved by stripping of surface components. The most extensive resolution was recently obtained with the aid of silicotungstate. Such particles require for oxidative phosphorylation the addition of several coupling factors as well as succinate dehydrogenase. (2) Starting with submitochondrial particles that have been degraded by trypsin and urea a resolution of the inner membrane proper containing an ATPase has been achieved. These experiments show that at least five components are required for the reconstitution of an oligomycin-sensitive ATPase: a particulate component, F1, Mg++, phospholipids, and Fc. Morphologically, the reconstituted ATPase preparations resemble submitochondrial particles. (3) Starting with intact mitochondria individual components of the oxidation chain have been separated from each other. The following components were required for the reconstitution of succinoxidase: succinate dehydrogenase, cytochrome b\, cytochrome c1, cytochrome c, cytochrome oxidase, phospholipids and Q10. The reconstituted complex had properties similar to those of phosphorylating submitochondrial particles; i.e., the oxidation of succinate by molecular oxygen was highly sensitive to antimycin.
Intra-Protein Interactions Across a Fluid Membrane as a Model for Biological Transport
Authors: Stein W. D.
Published: May 2004

A model is proposed for the mechanism of action of the glucose transport system of the human erythrocyte. The model is based on the possibility of there being interaction through the membrane between superficially disposed protein subunits, these units being embedded within the bimolecular lipid layer, anchored to the aqueous phase, perhaps mobile in the plane of each face of the membrane. The subunits have the ability to bind sugar and, when associated with the symmetrical protein at the opposite face of the membrane, transfer sugar across the membrane. Evidence for the model is presented. The possibility that this model may also be a model for the cell membrane as such is briefly touched upon.
The Effect of Osmotic Shock on Release of Bacterial Proteins and on Active Transport
Authors: Heppel Leon A.
Published: May 2004

Osmotic shock is a procedure in which Gram-negative bacteria are treated as follows. First they are suspended in 0.5 M sucrose containing ethylenediaminetetraacetate. After removal of the sucrose by centrifugation, the pellet of cells is rapidly dispersed in cold, very dilute, MgCl2. This causes the selective release of a group of hydrolytic enzymes. In addition, there is selective release of certain binding proteins. So far, binding proteins for D-galactose, L-leucine, and inorganic sulfate have been discovered and purified. The binding proteins form a reversible complex with the substrate but catalyze no chemical change, and no enzymatic activities have been detected. Various lines of evidence suggest that the binding proteins may play a role in active transport: (a) osmotic shock causes a large drop in transport activity associated with the release of binding protein; (b) transport-negative mutants have been found which lack the corresponding binding protein; (c) the affinity constants for binding and transport are similar; and (d) repression of active transport of leucine was accompanied by loss of binding protein. The binding proteins and hydrolytic enzymes released by shock appear to be located in the cell envelope. Glucose 6-phosphate acts as an inducer for its own transport system when supplied exogenously, but not when generated endogenously from glucose.
Swelling of the Transverse Tubular System in Frog Sartorius
Authors: Rapoport Stanley I. , Peachey L. D. , Goldstein D. A.
Published: May 2004

Electron microscopy shows that the transverse tubular system of frog sartorius swells in Ringer fluid in which NaCl is partially replaced by sucrose (sucrose isotonic solutions). At constant tonicity, the degree of swelling is roughly proportional to the decrease in ionic strength and to the sucrose concentration of the bathing solution. Swelling is time-dependent and reversible within 2 hr. The late after potential which follows a train of impulses is prolonged with swelling, but not to the extent expected from the model of Adrian and Freygang. This discrepancy remains unexplained, as does the mechanism of swelling of the transverse tubular system, although some suggestions are offered. One is that the transverse tubular system contains fixed charges and swells like a fixed charge gel.
The Dependence of the Oxygen-Concentrating Mechanism of the Teleost Eye (Salmo gairdneri) on the Enzyme Carbonic Anhydrase
Authors: Fairbanks Michael B. , Hoffert J. Russell , Fromm Paul O.
Published: May 2004

Microoxygen polarographic electrodes were constructed and used to measure oxygen tension (POO2) in the eyes of rainbow trout (Salmo gairdneri). The values obtained are compared with arterial blood and environmental water POO2 and indicate that there is an oxygen-concentrating mechanism in the eye supplying oxygen to the avascular retina. Anatomically similar retes suggest that the mechanism is similar to the one which exists in the swim bladder. Elimination of the arterial blood supply to the choroidal gland rete mirabile of the eye (through pseudobranchectomy) and the consequent lowering of ocular oxygen tensions implicate the choroidal gland as one of the major components of the oxygen-concentrating mechanism. After pseudobranchectomy the presence of ocular POO2 above that of arterial blood is indicative of a secondary structure in the eye capable of concentrating oxygen. Inhibition of carbonic anhydrase, using acetazolamide, is shown to result in complete suppression of the oxygen-concentrating mechanism. A hypothesis is advanced for the participation of retinal-choroidal and erythrocyte carbonic anhydrase in the oxygen-concentrating mechanism.
Dichroism of Photosensitive Pigment in Rhabdoms of the Crayfish Orconectes
Authors: Waterman Talbot H. , Fernández Hector R. , Goldsmith Timothy H.
Published: May 2004

Microspectrophotometric measurements of isolated crayfish rhabdoms illuminated transversely show that their photosensitive absorption exhibits a dichroic ratio of 2 in situ. The major absorption axis matches the axial direction of the closely parallel microvilli comprising the receptor organelle. Since these microvilli are regularly oriented transversely in about 24 layers, with the axes of the microvilli at 90° in alternate layers, transverse illumination of a properly oriented rhabdom displays alternate dichroic and isotropic bands. Because all the microvilli from any one cell share the same orientation, the layers of microvilli constitute two sets of orthogonal polarization analyzers when illuminated along the normal visual axis. Furthermore, since the dichroic ratio is 2 and transverse absorption in isotropic bands is the same as that in the minor absorbing axis of dichroic bands, the simplest explanation of the analyzer action is that the absorbing dipoles of the chromophores, as in rod and cone outer segments, lie parallel to the membrane surface but are otherwise randomly oriented. The rhabdom's functional dichroism thus arises from its specific fine structural geometry.
Analysis of the Effects of Calcium or Magnesium on Voltage-Clamp Currents in Perfused Squid Axons Bathed in Solutions of High Potassium
Authors: Rojas Eduardo , Taylor Robert E. , Atwater Illani , Bezanilla Francisco
Published: May 2004

Isolated axons from the squid, Dosidicus gigas, were internally perfused with potassium fluoride solutions. Membrane currents were measured following step changes of membrane potential in a voltage-clamp arrangement with external isosmotic solution changes in the order: potassium-free artificial seawater; potassium chloride; potassium chloride containing 10, 25, 40 or 50, mM calcium or magnesium; and potassium-free artificial seawater. The following results suggest that the currents measured under voltage clamp with potassium outside and inside can be separated into two components and that one of them, the predominant one, is carried through the potassium system. (a) Outward currents in isosmotic potassium were strongly and reversibly reduced by tetraethylammonium chloride. (b) Without calcium or magnesium a progressive increase in the nontime-dependent component of the currents (leakage) occurred. (c) The restoration of calcium or magnesium within 15–30 min decreases this leakage. (d) With 50 mM divalent ions the steady-state current-voltage curve was nonlinear with negative resistance as observed in intact axons in isosmotic potassium. (e) The time-dependent components of the membrane currents were not clearly affected by calcium or magnesium. These results show a strong dependence of the leakage currents on external calcium or magnesium concentration but provide no support for the involvement of calcium or magnesium in the kinetics of the potassium system.
Inactivation of the Potassium Conductance and Related Phenomena Caused by Quaternary Ammonium Ion Injection in Squid Axons
Authors: Armstrong Clay M.
Published: May 2004

Several analogues of the tetraethylammonium (TEA+) ion were injected into the giant axon of the squid, and the resultant changes in time course and magnitude of the potassium current (IK) were studied. For all the analogues used, three of the ethyl side chains of TEA+ were left unchanged, while the fourth chain was either lengthened or shortened. Increasing the length of this chain increased binding to the blocking site in the channel by a factor of roughly two for each added CH2 group. The effect on the rate of entry into the blocking site was relatively slight. Thus the concentration for half-suppression of gK decreased by about the same factor of two for each added CH2. All the analogues caused anomalous or ingoing rectification. The longest chain analogue used, pentyltriethylammonium ion, caused rapid inactivation of gK, and this inactivation had properties quite similar to gNa inactivation. The anomalous rectification and the gK inactivation caused by these compounds have the same basic mechanism.
The Effect of Ouabain and External Potassium on the Ion Transport of Rabbit Red Cells
Authors: Villamil M. F. , Kleeman C. R.
Published: May 2004

Na efflux of rabbit RBC is approximately 10 mmoles/kg wet weight. hr. One-half of this consists of a ouabain-insensitive exchange diffusion component. Ouabain inhibits 2.5 mmoles/kg.hr of Na efflux. K influx is 3.0 mmoles/kg.hr; 2.2 mmoles/kg.hr are inhibited by ouabain. In contrast with human RBC, ouabain inhibition of Na efflux and K influx of rabbit RBC is easily reversible. After 2 hr, ouabain inhibition of Na efflux is completely compensated for by increased internal Na concentration and Na efflux returns to initial levels. Removal of ouabain at this stage results in stimulation of the efflux by 4.3 mmoles/kg.hr. Na influx is initially not affected by ouabain but is increased by 2.4 mmoles/kg.hr after 2 hr incubation with the drug. Removal of K from normal Ringer does not affect Na efflux and increases Na influx by 1.6 mmoles/kg.hr. Addition of ouabain to K-free Ringer inhibits Na efflux and influx to the same extent (1.6 mmoles/kg.hr). Removal of Na from K-free Ringer has an inhibitory effect on efflux similar to that of ouabain. These findings suggest that the fraction of Na efflux inhibited by removal of external K is completely replaced by a new, ouabain-sensitive exchange diffusion of Na ions.
The Spectral Sensitivities of Single Cells in the Median Ocellus of Limulus
Authors: Nolte John , Brown Joel E.
Published: May 2004

The spectral sensitivities of single Limulus median ocellus photoreceptors have been determined from records of receptor potentials obtained using intracellular microelectrodes. One class of receptors, called UV cells (ultraviolet cells), depolarizes to near-UV light and is maximally sensitive at 360 nm; a Dartnall template fits the spectral sensitivity curve. A second class of receptors, called visible cells, depolarizes to visible light; the spectral sensitivity curve is fit by a Dartnall template with λmax at 530 nm. Dark-adapted UV cells are about 2 log units more sensitive than dark-adapted visible cells. UV cells respond with a small hyperpolarization to visible light and the spectral sensitivity curve for this hyperpolarization peaks at 525–550 nm. Visible cells respond with a small hyperpolarization to UV light, and the spectral sensitivity curve for this response peaks at 350–375 nm. Rarely, a double-peaked (360 and 530 nm) spectral sensitivity curve is obtained; two photopigments are involved, as revealed by chromatic adaptation experiments. Thus there may be a small third class of receptor cells containing two photopigments.
Studies on the Active Transport of Calcium in Human Red Cells
Authors: Lee Kwang Soo , Shin Bak Chang
Published: May 2004

The Ca++ transport mechanism in the red cell membrane was studied in resealed ghost cells. It was found that the red cell membrane can transport Ca++ from inside the cell into the medium against great concentration gradient ratios. Tracing the movement of 45Ca infused inside red cells indicated that over 95% of all Ca++ in the cells was transported into media in 20 min incubation under the optimum experimental conditions. The influence of temperature on the rate constant of transport indicated an activation energy of 13,500 cal per mole. The optimum pH range of media for the transport was between 7.5 and 8.5. As energy sources, ATP1, CTP, and UTP were about equally effective, GTP somewhat less effective, and ITP least effective among the nucleotides tested. The Ca++ transport does not appear to involve exchange of Ca++ with any monovalent or divalent cations. Also, it is not influenced by oligomycin, sodium azide, or ouabain in high concentrations, which inhibit the Ca++ transport in mitochondria or in sarcoplasmic reticulum. In these respects, the Ca++ transport mechanism in the red cell membrane is different from those of mitochondria and the sarcoplasmic reticulum.
Leak Current Rectification in Myxicola Giant Axons
Authors: Goldman L. , Binstock L.
Published: May 2004

Early leak current, i.e. for times similar to the time to peak of the transient current was measured in Myxicola giant axons in the presence of tetrodotoxin. The leak current-voltage relation rectifies, showing more current for strong depolarizing pulses than expected from symmetry around the holding potential. A satisfactory practical approximation for most leak corrections is constant resting conductance. The leak current-voltage curve rectifies less than expected from the constant field equation. These curves cannot be reconstructed by summing the constant field currents for sodium and potassium using a PNa/PK ratio obtained in the usual way, from zero current constant field fits to resting membrane potential data. Nor can they be reconstructed by summing the constant field current for potassium with that for any other single ion. They can be reconstructed, however, by summing the constant field current for potassium with a constant conductance component. It is concluded that the leak current and the resting membrane potential, therefore, are determined by multiple ionic components, at least three and possibly many. Arguments are presented suggesting that ion permeability ratios obtained in the usual way, by fitting the constant field equation to resting membrane potential data should be viewed with skepticism.
Energy Conversion in Bull Sperm Flagella
Authors: Rikmenspoel Robert , Sinton Sandra , Janick John J.
Published: May 2004

With the use of a specially developed incubation chamber the rates of motility, respiration, and fructolysis were measured simultaneously on semen samples. By inhibiting the respiration with antimycin A, and/or the fructolysis with 2-deoxyglucose, the rates of each of the two ATP-producing pathways could be reduced independently. In this way the ratio of the amount of free energy produced by respiration and by fructolysis could be varied at will from 1 to 0. In uninhibited preparations approximately 75% of the free energy derives from respiration, and 25% from fructolysis. By the use of the absolute rates of respiration, fructolysis, and motility, the efficiency of the conversion of free energy into hydrodynamic work was calculated. After correction for the decay of the preparation during the experiment, this conversion efficiency was found to be 30–45% lower for free energy from respiration than for free energy from fructolysis. The difference in distribution of the enzymes for fructolysis and respiration over the flagellum was ruled out as the cause of the efficiency difference. The respiration could be 70% inhibited by oligomycin. It is concluded that approximately one-third of the free energy from respiration is used for maintenance of the mitochondria.
Oscillation and Repetitive Firing in Squid Axons
Authors: Guttman Rita , Barnhill Robert
Published: May 2004

Space-clamped squid axons treated with low calcium and computed Hodgkin-Huxley (HH) axons were stimulated by steps of superthreshold current from 101 to 400% of the rheobasic value over a temperature range of 5–27°C. The natural frequency of sustained repetitive firing of real and computed axons depended weakly upon stimulus intensity and strongly upon temperature, with a Q10 of 2.7 (experimental) and 2.6 (computed). For real axons, but not the computed axon, the intervals between the first two spikes were shorter than between subsequent spikes. Constant spike frequencies from 75 Hz at low intensities and temperatures to 330 Hz at high intensities and temperatures were soon achieved. Subthreshold and superthreshold responses were sometimes intermixed in a train of responses from a real axon responding to a constant step of current, but not predicted by HH. The time interval following a spike was always longer than that following a subthreshold oscillation in slightly decalcified real axons, as Huxley and FitzHugh also found for computed axons. There was a bias toward spikes at the beginning of the train and toward subthreshold responses later on. Some repeated patterns were found, every second, third, or fourth response being a spike. Neither the HH equations nor the computed or experimental threshold behaviors show a critical temperature to support a membrane phase transition.
Transport Parameters in a Porous Cellulose Acetate Membrane
Authors: DiPolo R. , Sha'afi R. I. , Solomon A. K.
Published: May 2004

The transport parameters of a cellulose acetate membrane prepared from a mixture of cellulose acetate, formamide, and acetone, 25:25:50 by weight, were studied. The membrane consists of a thin, porous layer, the skin, in series with a thick, highly porous layer, the coarse support. In the skin the diffusional permeability coefficient, ω, of a number of small amides and alcohols depends critically upon the partition coefficient, Ks, the size of the molecule, and the apparent hydrogen-bonding ability, Ns, of the solute. These observations are in general agreement with our earlier conclusions on the properties of nonporous membranes. On the other hand, the corrected reflection coefficient, σ', is not a very sensitive function of either Ns or Ks taken separately. The correlation between σ' and molecular diameter is reasonably good; however, it is much improved when both Ns and Ks are taken into consideration. Isotope interaction was also studied in the present preparation and was found to provide only a small (5–8%) contribution to the diffusional permeability coefficient of ethylene glycol. The contribution of solute-water friction was found to be less than 24% of the total solute friction.
Kinetic Analyses of Calcium Movements in Cell Cultures
Authors: Borle André B.
Published: May 2004

Calcium compartments and fluxes were measured by kinetic analyses in kidney cell suspensions in a three-compartment closed system. The fast phase influx and compartment size increase linearly with the medium calcium and the half-time of exchange is only 1.3 min which suggests that the fast component is extracellular. The slow phase compartment rises linearly from 0.1 to 0.5 mmole calcium/kg cell water when the medium calcium is raised from 0.02 to 2.5 mM. The slow phase calcium influx exhibits the pattern of saturation kinetics with a Vmax of 0.065 µµmole cm-2 sec-1 and a Km of 0.3 mM indicating that it is a carrier-mediated transport process. PTH has no effect on the fast phase of calcium influx, but increases both calcium influx and the calcium pool size of the slow component. The maximum effect is obtained at medium calcium concentration of 1.3 mM. Below 0.3 mM extracellular calcium, the effects of the hormone cannot be demonstrated. PTH increases the Vmax of calcium influx from 0.065 to 0.128 µµmole cm-2 sec-1 while the Km rises from 0.3 to 1.15 mM. These findings suggest that PTH increases the translocation of the calcium-carrier complex across the membrane and not the carrier concentration or its binding affinity for calcium.
Ion Metabolism in a Halobacterium
Authors: Ginzburg Margaret , Sachs Laura , Ginzburg B. Z.
Published: May 2004

Work is described on the changes in cell ions during growth of cultures of a species of Halobacterium isolated from the Dead Sea. Cell K concentration fell from 5.5 to 3.8 moles per kg cell water during the logarithmic phase of growth and maintained the latter value during the stationary phase (initial medium concentration, 7 mM). Cell Na and Cl followed a complex series of roughly parallel changes. The logarithmic phase ion concentrations were: Na, 1.0–2.3 moles/kg cell water; Cl, 2.3–3.7 moles/kg cell water. The final stationary phase values were: Na, 0.5 moles/kg cell water; Cl, 2.3–2.9 moles/kg cell water (medium NaCl concentration, 3.9 Molal). It is suggested that most of the K+ is bound within the cytoplasm.
Electrical Transmission among Neurons in the Buccal Ganglion of a Mollusc, Navanax inermis
Authors: Levitan H. , Tauc L. , Segundo J. P.
Published: May 2004

The opisthobranch mollusc, Navanax, is carnivorous and cannibalistic. Prey are swallowed whole by way of a sudden expansion of the pharynx. The buccal ganglion which controls this sucking action was isolated and bathed in seawater. Attention was focused upon 10 identifiable cells visible on the ganglion's rostral side. Two cells were observed simultaneously, and each was penetrated with two glass microelectrodes, one for polarizing the membrane and the other for recording membrane potential variations. The coupling coefficients for direct current flow and action potentials of several identified cells were tabulated. Attenuation was essentially independent of the direction of current flow, but depended upon the relative size of the directly and indirectly polarized cells. The attenuation of subthreshold sinusoidally varying voltages increased with frequency above about 1 Hz. The coupling coefficient for spikes was lower than for DC due to greater high frequency attenuation. There is considerable similarity in the spontaneous PSP's of all cells, which is not due to the electrical coupling but to input from a common source. The 10 cells were not chemically interconnected but some were electrically connected to interneurons which fed back chemically mediated PSP's. The feedback can be negative or positive depending upon the membrane potential of the postsynaptic cell. We conclude that electrical coupling among the 10 cells plays a minor role in sudden pharyngeal contractions but that the dual electrical-chemical coupling with interneurons may be important in this respect.
Effects of Caffeine on Crayfish Muscle Fibers
Authors: Chiarandini Dante J. , Reuben John P. , Brandt Philip W. , Grundfest Harry
Published: May 2004

Contractions are evoked in single muscle fibers of crayfish by intracellular as well as extracellular applications of caffeine. Responses to external applications in concentrations above 2 mM could be induced indefinitely. With concentrations above 5 mM the caffeine-induced responses were highly repeatable. Tensions were transient even when the caffeine remained in the bath. There was no change in resting potential, but during the contraction the effective resistance decreased about 10%. A number of factors (change in pH, Ca, K, and Cl) modified the responses. The time course of the tension was greatly prolonged when the transverse tubular system (TTS) was s swollen and was again shortened when the TTS was caused to shrink. An increased permeability to Ca induced by caffeine was evidenced by the transformation of the normally graded electrical responses to Ca spikes, which are insensitive to tetrodotoxin. The overshoot is a function of both external Ca and caffeine. A 10-fold change in Ca changed the overshoot by 19 mv in the presence of 10 mM caffeine and by 29 mv in 80 mM caffeine. The role of the increased permeability to Ca for caffeine-induced contractions will be analyzed in the accompanying paper.
The Membrane Potential of Acetabularia mediterranea
Authors: Saddler H. D. W.
Published: May 2004

The cytoplasm of an Acetabularia cell is normally at a potential of about -170 mv relative to the external solution; the vacuole is also at this potential. Although there is strict flux equilibrium for all ions, the potential is more negative than the Nernst potentials of any of the permeating ions. Darkness, CCCP, low temperature, and reducing [Cl-]o by a factor of 25 all rapidly depolarize the membrane and inhibit Cl- influx. Some of these treatments do not inhibit the effluxes of K+ and Na+. Increasing [K+]o also depolarizes the membrane both under normal conditions and at low temperature; in the latter case the membrane is partially depolarized in normal seawater (low [K+]o) and in high [K+]o positive potentials of up to +15 mv are attained. It is concluded that the membrane potential is controlled by the electrogenic influx of Cl-, and also, at least in some circumstances, by the diffusion of K+. In addition, it is suggested that electrogenic efflux of H+ may be important in transient nonequilibrium situations. An Appendix deals with the interpretation of simple nonsteady-state tracer kinetic data.
The Dynamic Characteristics of Color-Coded S-Potentials
Authors: Spekreijse Henk , Norton Alan L.
Published: May 2004

A linear analysis approach has been applied to determine the dynamic characteristics of the color-coded S-potentials. Using a sinusoidally modulated light stimulus it could be shown that the monophasic S-potential as well as each of the different components of biphasic and triphasic S-potentials behaves linearly. However, for high modulation depths and high average intensities nonlinear effects, such as saturation, become obvious. The transfer characteristics of the monophasic potentials and each component of the biphasic and triphasic potentials are indistinguishable. Their latencies, however, differ. These findings suggest that the three different types of S-potentials not only originate from functionally comparable cells but also that the dynamic characteristics of the cells presynaptic to the S-potential sources are identical.
The Ion Permeability Induced in Thin Lipid Membranes by the Polyene Antibiotics Nystatin and Amphotericin B
Authors: Cass Albert , Finkelstein Alan , Krespi Vivian
Published: May 2004

Characteristics of nystatin and amphotericin B action on thin (<100 A) lipid membranes are: (a) micromolar amounts increase membrane conductance from 10-8 to over 10-2 Ω-1 cm-2; (b) such membranes are (non-ideally) anion selective and discriminate among anions on the basis of size; (c) membrane sterol is required for action; (d) antibiotic presence on both sides of membrane strongly favors action; (e) conductance is proportional to a large power of antibiotic concentration; (f) conductance decreases ∼104 times for a 10°C temperature rise; (g) kinetics of antibiotic action are also very temperature sensitive; (h) ion selectivity is pH independent between 3 and 10, but (i) activity is reversibly lost at high pH; (j) methyl ester derivatives are fully active; N-acetyl and N-succinyl derivatives are inactive; (k) current-voltage characteristic is nonlinear when membrane separates nonidentical salt solutions. These characteristics are contrasted with those of valinomycin. Observations (a)–(g) suggest that aggregates of polyene and sterol from opposite sides of the membrane interact to create aqueous pores; these pores are not static, but break up (melt) and reform continuously. Mechanism of anion selectivity is obscure. Observations (h)–(j) suggest—NH3+ is important for activity; it is probably not responsible for selectivity, particularly since four polyene antibiotics, each containing two—NH3+ groups, induce ideal cation selectivity. Possibly the many hydroxyl groups in nystatin and amphotericin B are responsible for anion selectivity. The effects of polyene antibiotics on thin lipid membranes are consistent with their action on biological membranes.
The Defensive Role of the Interferon System
Authors: Baron Samuel
Published: May 2004

The evidence relating the interferon system to the infectious process has been examined. The available evidence supports the view that the interferon system is an important component of the body's nonimmune defenses, which are probably the major causes of recovery from already established virus infections of body tissues. The interferon system can also serve to limit virus spread through the bloodstream. Factors which may influence the interferon system and thereby influence virus infection have been considered. Finally, evidence is presented which indicates that the interferon system is one of the determinants of virulence of certain viruses and is one of the determinants of some persistent virus infections.
Interrelationships of Interferon and Immunity During Viral Infections
Authors: Glasgow Lowell A.
Published: May 2004

Interferon is one determinant of host resistance. The immune responses, cellular or humoral, are other components. Cell-mediated responses appear to be involved in host resistance to certain viral infections, particularly the herpesvirus group and vaccinia virus. It is suggested that immune and interferon responses may complement one another and contribute to host resistance. The relative importance of each component depends upon the virus-host interaction. Finally, evidence has been presented which suggests that production of interferon as a result of antigen-sensitized cell interaction may further link these two components of the host response.
Interferon and Interferon Inducers in the Treatment of Malignancies
Authors: Levy Hilton B. , Riley Freddie , Margolis Sam
Published: May 2004

The mechanism of the antitumor action of polyinosinic-polycytidylic acid is probably multifaceted. The compound induces the synthesis of interferon, and interferon probably is active against some tumors. Poly I:poly C alters protein and RNA synthesis in tissue culture. It specifically inhibits such macromolecule synthesis in tumors in vivo, while having less inhibitory action on synthesis in normal organs, or it may actually enhance. Finally, poly I:poly C strongly enhances graft vs. host rejection mechanisms, which may play a role in the rejection of some tumors.
Desensitization of Gamma Aminobutyric Acid (GABA) Receptors in Muscle Fibers of the Crab Cancer borealis
Authors: Epstein René , Grundfest Harry
Published: May 2004

Carcinus muscle fibers respond to γ-aminobutyric acid (GABA) with a conductance increase that subsides rather rapidly. In the larger fibers which have low input resistance the decrease may disappear within 2 min. The inhibition of the excitatory postsynaptic potentials (EPSP's) by GABA nevertheless persists as long as the drug is applied. The subsidence of the increased conductance indicates that the membrane of the inhibitory synapses has become desensitized to GABA. The persistence of inhibition of the EPSP's appears to be due to an action of the drug on the presynaptic terminals of the excitatory axons which reduces or blocks the secretory activity that releases the excitatory transmitter.
Double-Stranded Polynucleotides as Interferon Inducers
Authors: Field A. K. , Tytell A. A. , Lampson G. P. , Nemes M. M. , Hilleman M. R.
Published: May 2004

A discussion of factors considered influential in making a polynucleotide an efficient inducer of interferon was presented. These factors were double-strandedness of the polynucleotides, the sugar moiety of the polynucleotides, thermal stability, resistance to enzymatic degradation, and molecular size of the polynucloetides. Recent developments concerning interferon induction during virus infection were also discussed.
The Uptake of a Labeled Double-Stranded Polynucleotide by Cultured Rabbit Kidney Cells: An Electron Microscopic Study
Authors: Prose Philip H. , Friedman-Kien Alvin , Vilček Jan
Published: May 2004

Polyribocytidylate-3H-polyriboinosinate (rC-3H:rI) enters cultured rabbit kidney cells from the surrounding medium within ½ hr after exposure. Grains are found in the cytoplasm, nucleus, and nucleolus. At 2 hr, grains are localized predominantly over the nucleolar regions. Subsequently, the grains in the nucleus become dispersed. A specific receptor site for the initiation of interferon production was not revealed.
Contribution of the Excluded Volume of Bovine Serum Albumin for Solute Molecules to the Apparent Nonsolvent Water
Authors: Borst-Pauwels G. W. F. H. , Goldstein D. A.
Published: May 2004

Addition of a macromolecule to a solution will give rise to a large excluded volume for the centers of the solute molecules. This will cause an apparent increase in solute concentration which is of the same order of magnitude as that associated with the nonsolvent volumes reported in the literature. A critical examination of one of the procedures used for the determination of nonsolvent water—the vapor pressure method of Hill—is given, and it is concluded that, with the use of this method, it is impossible to detect any significant nonsolvent water surrounding bovine albumin for either sugars or polyols. Generally, data reported in the literature for the nonsolvent water of proteins or other macromolecules will be too high unless they are corrected for the excluded volume.
Effects of Monovalent Cations on the Sodium-Alanine Interaction in Rabbit Ileum
Authors: Frizzell Raymond A. , Schultz Stanley G.
Published: May 2004

H, K, Rb, and Li inhibit Na-dependent alanine influx across the brush border of rabbit ileum. Kinetic analysis indicates that H and K behave as competitive inhibitors of influx so that increasing the concentration of H or K in the mucosal solution is kinetically indistinguishable from decreasing the Na concentration. In addition the coupling between alanine and Na influxes is markedly reduced at pH 2.5. With the exception of H and Li, none of these monovalent cations significantly affects carrier-mediated alanine influx in the absence of Na indicating that their inhibitory effects are largely restricted to the Na-dependent fraction of influx. Increasing H concentration from 0.03 to 3 mM does not affect influx in the absence of Na but markedly inhibits influx in the presence of Na. Li significantly enhances alanine influx in the absence of Na. Ag, UO2, and La also inhibit the Na-dependent fraction of alanine influx. These findings suggest that anionic groups having a pKa of approximately 4 are involved in the interaction between Na and the alanine-carrier complex; present evidence implicates carboxylate groups however, phosphoryl residues cannot be ruled out. The previously proposed kinetic model for the Na-alanine interaction has been extended to accommodate these effects of H and other monovalent cations. The mechanistic and physiological implications of these findings are discussed.
Visual Adaptation in the Retina of the Skate
Authors: Dowling John E. , Ripps Harris
Published: May 2004

The electroretinogram (ERG) and single-unit ganglion cell activity were recorded from the eyecup of the skate (Raja erinacea and R. oscellata), and the adaptation properties of both types of response compared with in situ rhodopsin measurements obtained by fundus reflectometry. Under all conditions tested, the b-wave of the ERG and the ganglion cell discharge showed identical adaptation properties. For example, after flash adaptation that bleached 80% of the rhodopsin, neither ganglion cell nor b-wave activity could be elicited for 10–15 min. Following this unresponsive period, thresholds fell rapidly; by 20 min after the flash, sensitivity was within 3 log units of the dark-adapted level. Further recovery of threshold was slow, requiring an additional 70–90 min to reach absolute threshold. Measurements of rhodopsin levels showed a close correlation with the slow recovery of threshold that occurred between 20 and 120 min of dark adaptation; there is a linear relation between rhodopsin concentration and log threshold. Other experiments dealt with the initial unresponsive period induced by light adaptation. The duration of this unresponsive period depended on the brightness of the adapting field; with bright backgrounds, suppression of retinal activity lasted 20–25 min, but sensitivity subsequently returned and thresholds fell to a steady-state value. At all background levels tested, increment thresholds were linearly related to background luminance.
Characteristics of the Amino Acid Transport System in the Mucosal Border of Rabbit Ileum
Authors: Hajjar Jean Jacques , Curran Peter F.
Published: May 2004

The specificity of the neutral amino acid transport system in the brush border was examined by studying the ability of amino acid analogues to inhibit the unidirectional influx of phenylalanine from mucosal solution into the cells. Effects were evaluated in terms of the affinity of various substrates for the amino acid site in the transport system. The affinity of amino acids for the site was proportional to the number of carbon atoms in the side chain. Electron-withdrawing substituents in the ring of phenylalanine increased affinity and electron-releasing groups decreased affinity. Removal of the α-amino group from phenylalanine decreased affinity by a factor of approximately 50 and removal of the carboxyl group decreased affinity 12-fold. Effects on affinity of variations in the side chain of the amino acid can be comparable in magnitude to that of the carboxyl group. The effect of sodium ion on the transport system appears to be similar for all compounds tested.
Potassium Exchange and Afterpotentials in Frog Sartorius Muscles Treated with Glycerol
Authors: Henderson Edward G.
Published: May 2004

The potassium exchange properties of glycerol-treated sartorius muscles of the frog were determined. Potassium (42K) uptake, efflux, and net flux were measured in the presence of glycerol and at various times after exposure to glycerol and return to isotonic Ringer solution. Potassium uptake was not altered by the presence of glycerol but was reduced on the average 53% after glycerol treatment. Efflux transiently increased in the presence of glycerol and was reduced 37% after glycerol removal. Consequently, there was a net loss of intracellular potassium as well as a gain of sodium. In contrast to the irreversible alterations of potassium exchange induced by glycerol treatment, action potentials with normal negative afterpotentials (N.A.P.) were elicited 4–5 hr after glycerol removal. The reappearance of the N.A.P. was associated with a return of the membrane potential to normal values (90 ± 2 mv). However, the response of these muscles to reduced extracellular potassium was anomalous. In K+-free Ringer solution the average resting membrane potential was 74 ± 3 mv and a positive afterpotential of 11 ± 3 mv was associated with the action potential.
Spectral Sensitivity Studies on the Visual System of the Praying Mantis, Tenodera sinensis
Authors: Sontag Charles
Published: May 2004

In these studies a constant ERG response was used as a measure of visual sensitivity to different wavelengths of light. The dark-adapted compound eye of Tenodera sinensis is dominated by a single class of photoreceptors. with a major peak of sensitivity at about 510–520 nm, and with a minor peak of sensitivity in the near-ultraviolet region at about 370 nm. The dark-adapted dorsal ocellus does not contain a homogeneous population of sensory receptors. The sensitivity function of the dark-adapted ocellus to longer wavelength light (yellow and red) is determined by a single receptor with a major peak of sensitivity in the green at 510–520 nm with some sensitivity in the near-ultraviolet. Sensitivity at shorter wavelengths (near-ultraviolet and blue), however, involves the stimulation of both this and a near-ultraviolet-sensitive receptor with a maximum sensitivity at about 370 nm. Anatomically, the sensory cells of the dorsal ocellus of Tenodera were determined histologically to be grouped into two distinct regions, each group making its own separate contribution to the ocellar nerve. This may represent the separation of two different photoreceptor types in the ocellus of the mantis.
Theoretical Analysis of Net Tracer Flux Due to Volume Circulation in a Membrane with Pores of Different Sizes
Authors: Patlak Clifford S. , Rapoport Stanley I.
Published: May 2004

When osmotic pressure across an artificial membrane, produced by a permeable electrically neutral solute on one side of it, is balanced by an external pressure difference so that there is no net volume flow across the membrane, it has been found that there will be a net flux of a second electrically neutral tracer solute, present at equal concentrations on either side of the membrane, in the direction that the "osmotic" solute diffuses. This has been ascribed to solute-solute interaction or drag between the tracer and the osmotic solutes. An alternative model, presented here, considers the membrane to have pores of different sizes. Under general assumptions, this "heteroporous" model will account for both the direction of net tracer flux and the observed linear dependence of unidirectional tracer fluxes on the concentration of the osmotic solute. The expressions for the fluxes of solutes and solvent are mathematically identical under the two models. An inequality is derived which must be valid if the solute interaction model and/or the heteroporous model can account for the data. If the inequality does not hold, then the heteroporous model alone cannot explain the data. It was found that the inequality holds for most published observations except when dextran is the osmotic solute.
Magnesium in Single Skeletal Muscle Cells of Balanus
Authors: Page Ernest , Mobley Bert A. , Johnson Margaret , Upshaw Judy E.
Published: May 2004

Single skeletal muscle cells of Balanus contain 48 ± 1 mmoles magnesium/kg dry weight. Although 28Mg can be shown either to enter the cells or to be bound to the cell surface within less than 10 min, only 2.1 ± 0.3% of cellular or cell surface Mg exchanges with this isotope even after several hours. Glycerinated cells washed out in Tris buffer at low ionic strength retain ∼70% of the Mg present in intact cells. About 85% of this Mg is removed by extraction with KCl or NaCl at concentrations of K and Na which prevail in intact cells, as well as by pyrophosphate, Tris-ATP, or reduction of the ionized Mg concentration to 1 µM. Lowering the ionized Mg concentration to 0.1 µM does not further reduce the Mg content of glycerinated cells. The pH dependence of KCl-inextractable Mg suggests that more than one class of binding sites is involved. A significant fraction of the KCl-inextractable Mg bound to glycerinated cells fails to exchange with 28Mg even after long equilibration. It is suggested that this fraction may be actin-bound Mg incorporated into the thin filaments during the polymerization of actin.
The Kinetics of Sodium Transport in the Toad Bladder
Authors: Finn Arthur L. , Rockoff Maxine L.
Published: May 2004

A compartmental model of toad bladder sodium content has been developed, whereby it is possible to measure the four unidirectional fluxes across the opposite faces of the transport compartment, as well as the amount of sodium in the compartment. 24Na is added to the mucosal medium of a short-circuited bladder mounted between halves of a chamber in which the fluid is stirred by rotating impellers. After a steady state is reached, nonradioactive medium is flushed through both sides of the chamber, collected, and counted. The data from each chamber are fitted to sums of exponentials and interpreted in terms of conventional compartmental analysis. Three exponentials are required, with half-times of 0.2, 2.2, and 14.0 min. It is shown that the first of these represents chamber washout, the second the transport pool, and the third a tissue compartment which is not involved in active sodium transport and which does not communicate with the transport pool. The second compartment contains 10.5 µEq of sodium per 100 mg dry weight, an amount equal to approximately 30% of total tissue sodium. The results also indicate, as expected from electrophysiological data, that the mucosal-facing side of the transport compartment is over 10 times as permeable to sodium as the serosal, or pump, side.