STUDIES ON THE PHYSIOLOGICAL EFFECTS OF NON-POLAR-POLAR ORGANIC ELECTROLYTES : I. THE INFLUENCE UPON THE RESTING POTENTIAL OF FROG MUSCLE

1. The commonly used detergents have a poisonous effect, which is due to the non-polar-polar configuration of their organic anion. The non-polar organophilic half of the ion is built up by a long chain of alkyl radicals (8 to 18 carbon atoms), the polar hydrophilic half by a sulfonate or sulfate. If brought into contact with the organic surface membrane of a cell, this structure, due to the strong attachment of the alkyl chains to its surface, and due to the pull of the hydrophilic part towards the surrounding water, is subjected to a heavy stress terminating in tearing to pieces the membrane (by denaturing and loosening the membrane components; bacteriolysis, cytolysis). Correspondingly, with frog muscle, one end of which has been treated with the detergent solution, an irreversible negative injury potential is produced. 2. Applying, instead, the compounds bearing short chains of alkyl radicals (1 to 6 carbon atoms), producing less stress on the membrane and correspondingly a slighter derangement of its architecture, a reversible positive resting potential appears. This is interpreted to be the effect of the non-polar part of the anion, which, due to its surface activity, intrudes into the pores of the membranes, notwithstanding the negative charge of their walls. 3. The short chained detergents seem to be replaceable by various organic "semidetergents," the organophilic behavior of their anion being represented by a slight chemical affinity (NH₂), the hydrophilic by the effect of a carboxyl group (COO) instead of sulfate or sulfonate. The effect of the semidetergents on muscle is a positive reversible potential. Their physiological significance may be visualized as a functional activation.     

THE INFLUENCE OF ELECTROLYTES ON THE STABILITY OF RED BLOOD CORPUSCLE SUSPENSIONS

Two types of stability are observed in suspensions of red blood cells. In weak concentrations of electrolytes the stability depends on the electric charge of the cells and suspension is unstable below a certain critical P.D. In strong concentrations of electrolyte, the stability bears no relation to the charge.     

NATURE OF THE RETARDING INFLUENCE OF THE THYMUS UPON AMPHIBIAN METAMORPHOSIS

1. Though thymus-fed salamander larvæ often metamorphose normally, thymus feeding sometimes retards and in rare cases inhibits metamorphosis completely. 2. The addition of normal food to a thymus diet abolishes the inhibitory effect of the thymus. 3. Addition of a small quantity of iodothyrin leads rapidly to precocious metamorphosis of thymus-fed larvæ. 4. The inhibitory effect of the thymus is not due to a specific inhibiting substance in the thymus, but to the absence from the thymus of a substance required to develop the thyroid to the secretory state.     

STUDIES CONCERNING THE NATURE OF THE SECRETORY ACTIVITY OF THE ISOLATED RINGER-PERFUSED FROG LIVER : II. THE INHIBITORY AND THE PROMOTING INFLUENCE OF ORGANIC ELECTROLYTES AND NON-ELECTROLYTES UPON THE SECRETION OF DYESTUFFS

The ability of the isolated Ringer-perfused frog liver, to concentrate dyestuffs in its secretion several hundred times, can be abolished entirely and reversibly by replacing in the Ringer solution about 1/8 of the NaCl by the isosmotic amount of a surface-inactive non-electrolyte (disaccharide, hexose, pentose, polyhydric alcohol, amino acid, acid amide) or electrolyte (salts of lower fatty acids, hydroxyl carboxylic, and dicarboxylic acids). This effect is not dependent upon changes in the perfusion rate. The opposite effect, promotion of secretory activity, can be brought about by polar-non-polar electrolytes (salts of higher fatty acids, bile acids, and other aromatic carboxylic acids, aromatic sulfonic acids) and surface-active non-electrolytes (anesthetics, alkaloids, digitonin). However, reversibility of this effect cannot be regularly observed, since cytolysis is frequently the end result. Suitable concentrations of inhibitory and promoting substances, simultaneously applied, counteract each other. Inhibitory and promoting substances, in general, exhibit opposite effects upon the dispersion of colloids (starch, lecithin, gelatin). The correlation between the physicochemical and the physiological action of the organic compounds is discussed.     

THE INFLUENCE OF pH UPON THE CONCENTRATION POTENTIALS ACROSS THE SKIN OF THE FROG

The production of concentration P.D.''s across the skin of the frog is very intimately related to the pH of the applied solutions. On the alkaline side of an isoelectric point the dilute solution is electropositive; on the acid side this solution becomes electronegative. When the pH is suddenly lowered from a value more alkaline than this isoelectric point to one considerably more acid the change in polarity may occur within a few seconds. The effect is reversible. When a series of unbuffered solutions at different pH values are applied reversal curves may be obtained. When the concentration gradient is .1 N-.001 N KCl the reversal points lie between pH 4.1 and 4.8. When studied in acetate buffers this electromotive reversal is found to be closely correlated with the electrical charge upon the membrane, as determined by electroendosmosis through it. Reversal occurs between pH 4.9 and 5.2. It is concluded that the electromotive behavior of this material is controlled by some ampholyte, or group of ampholytes, within the membrane. This ampholyte is probably a protein. On both sides of their isoelectric point these membranes, in common with protein membranes, behave as if they retarded or prevented the movement through them of ions of the same electrical sign as they themselves bear, while permitting the movement of ions of the opposite sign. It is suggested that this correlation arises because of electrostatic effects between the charged surfaces and ions in the solution.     

THE INFLUENCE OF ROENTGEN RAYS UPON THE NITROGEN FIXATION BY AZOTOBACTER

The influence of graded x-ray doses upon nitrogen fixation and respiration by Azotobacter was studied by means of the Warburg method. It was found that nitrogen fixation decreases approximately linearly with increasing x-ray doses. Respiration in contrast is affected only indirectly through some inhibition of cell multiplication. Small doses of x-ray often produce a slight and transient increase in the rate of oxygen uptake.