Showing papers in "The Journal of Physiology in 1952"

A quantitative description of membrane current and its application to conduction and excitation in nerve

Abstract: This article concludes a series of papers concerned with the flow of electric current through the surface membrane of a giant nerve fibre (Hodgkinet al, 1952,J Physiol116, 424–448; Hodgkin and Huxley, 1952,J Physiol116, 449–566) Its general object is to discuss the results of the preceding papers (Section 1), to put them into mathematical form (Section 2) and to show that they will account for conduction and excitation in quantitative terms (Sections 3–6)

Currents carried by sodium and potassium ions through the membrane of the giant axon of Loligo

Abstract: In the preceding paper (Hodgkin, Huxley & Katz, 1952) we gave a general description of the time course of the current which flows through the membrane of the squid giant axon when the potential difference across the membrane is suddenly changed from its resting value, and held at the new level by a feed-back circuit ('voltage clamp' procedure). This article is chiefly concerned with the identity of the ions which carry the various phases of the membrane current. One of the most striking features of the records of membrane current obtained under these conditions was that when the membrane potential was lowered from its resting value by an amount between about 10 and 100 mV. the initial current (after completion of the quick pulse through the membrane capacity) was in the inward direction, that is to say, the reverse ofthe direction of the current which the same voltage change would have caused to flow in an ohmic resistance. The inward current was of the right order of magnitude, and occurred over the right range of membrane potentials, to be the current responsible for charging the membrane capacity during the rising phase of an action potential. This suggested that the phase of inward current in the voltage clamp records might be carried by sodium ions, since there is much evidence (reviewed by Hodgkin, 1951) that the rising phase of the action potential is caused by the entry of these ions, moving under the influence of concentration and potential differences. To investigate this possibility, we carried out voltage clamp runs with the axon surrounded by solutions with reduced sodium concentration. Choline was used as an inert cation since replacement of sodium with this ion makes the squid axon completely inexcitable, but does not reduce the resting potential (Hodgkin & Katz, 1949; Hodgkin, Huxley & Katz, 1949).

Spontaneous subthreshold activity at motor nerve endings

Abstract: The present study arose from the chance observation that end-plates of resting muscle fibres are the seat of spontaneous electric discharges which have the character of miniature end-plate potentials. The occurrence of spontaneous subthreshold activity at an apparently normal synapse is of some general interest, and a full description will be given here of observations which have been briefly reported elsewhere (Fatt & Katz, 1950a).

Measurement of current-voltage relations in the membrane of the giant axon of Loligo.

Abstract: The importance of ionic movements in excitable tissues has been emphasized by a number of recent experiments. On the one hand, there is the finding that the nervous impulse is associated with an inflow of sodium and an outflow of potassiuim (e.g. Rothenberg, 1950; Keynes & Lewis, 1951). On the other, there are experiments which show that the rate of rise and amplitude of the action potential are determined by the concentration of sodium in the external medium (e.g. Hodgkin & Katz, 1949 a; Huxley & Stiimpffi, 1951). Both groups of experiments are consistent with the theory that nervous conduction depends on a specific increase in permeability which allows sodium ions to move from the more concentrated solution outside a nerve fibre to the more dilute solution inside it. This movement of charge makes the inside of the fibre positive and provides a satisfactory explanation for the rising phase of the spike. Repolarization during the falling phase probably depends on an outflow of potassium ions and may be accelerated by a process which increases the potassium permeability after the action potential has reached its crest (Hodgkin, Huxley & Katz, 1949).

The dual effect of membrane potential on sodium conductance in the giant axon of Loligo

Abstract: This paper contains a further account of the electrical properties of the giant axon of Loligo. It deals with the 'inactivation' process which gradually reduces sodium permeability after it has undergone the initial rise associated with depolarization. Experiments described previously (Hodgkin & Huxley, 1952a, b) show that the sodium conductance always declines from its initial maximum, but they leave a number of important points unresolved. Thus they give no information about the rate at which repolarization restores the ability of the membrane to respond with its characteristic increase of sodium conductance. Nor do they provide much quantitative evidence about the influence of membrane potential on the process responsible for inactivation. These are the main problems with which this paper is concerned. The experimental method needs no special description, since it was essentially the same as that used previously (Hodgkin, Huiley & Katz, 1952; Hodgkin & Huxley, 1952b).

The electrical constants of Purkinje fibres.

Abstract: The aim of the present work was to measure the myoplasm resistance and the membrane resistance and capacity in Purkinje fibres of the mammalian heart. A knowledge of these characteristics is important in any discussion of cardiac excitation and conduction, and may also be of interest to those concerned with the movement of ions through cell membranes. The theoretical method employed was similar in principle to that introduced by Hodgkin & Rushton (1946). This is based on the assumption that a single fibre can be regarded as a cable-like structure with a core of well-conducting protoplasm and a thin surface membrane having a high resistance and a large capacity per unit area. In the present case the analysis was simplified by keeping the fibre in a large volume of saline and using internal electrodes to apply current and to record potential. This has the advantage that fewer independent measurements are needed in order to determine the basic constants of the fibre. The equations of cable theory are usually applied to a uniform fibre of infinite length, while the fibres of the cardiac syncytium fuse with one another at distances of less than 1 mm. The difficulties arising from this situation were reduced by using single fibres in the Purkinje system of the kid which were found to be free from interconnexions for a length of a few mm and by making use of a phenomenon characteristic for heart muscle, the 'healing-over' of cut surfaces. THEORY

Vascular reactions to histamine, histamine-liberator and leukotaxine in the skin of guinea-pigs.

Abstract: A substantial increase in capillary permeability is a feature of acute inflammation in bacterial infections. The present investigation is part of an attempt to prove an old hypothesis, namely, that this increase in permeability is mediated by histamine. A comparative study was made of histamine, of the histamineliberator 48/80, a condensation product ofp-methoxyphenylethylmethylamine and formaldehyde (Baltzly, Buck, de Beer & Webb, 1949), and of leukotaxine (Menkin, 1936, 1938a, b). In animals with a recently injected vital dye in their blood, the intradermal injection of substances that increase permeability of the blood vessels is followed by an accumulation of dye at the site of injection, presumably due to the passage of an excess of dye-stained plasma into the tissue spaces. When the blood flow and the vascular bed of the skin are relatively constant, differences in the size and intensity of stained areas of skin reflect differences in vascular permeability, and may be used to investigate the properties of substances that increase permeability in this way. Our work was confined to the skin of guinea-pigs, partly because much is already known about skin reactions to toxins and other inflammatory agents, and partly because it is a tissue readily studied in the intact and unanaesthetized animal-an important consideration with phenomena which, like the passage of dye through vascular endothelium, are peculiarly dependent on the state of the blood vessels in the tissue under test.

Eye movements during fixation

Abstract: Argyle, M., & Cook, M. (1976). Gaze and mutual gaze. Cambridge, UK: Cambridge University Press. Henderson, J. M., & Ferreira, F. (Eds.). (2004). The integration of language, vision, and action: Eye movements and the visual world. New York: Psychology Press. Richardson, D. C., Dale, R., & Kirkham, N. Z. (2007). The art of conversation is coordination: Common ground and the coupling of eye movements during dialogue. Psychological Science, 18(5), 407–413.

Action currents in single afferent nerve fibres elicited by stimulation of the skin of the toad and the cat.

Abstract: conclusions. With this technique it is easy to record sensory discharges in single nerve fibres which develop overwhelmingly large action potentials or in fibres with especially low threshold for sensory stimuli. It is, however, extremely difficult to explore the behaviour of nerve endings which on stimulation give rise to a limited number of small action potentials, because the discharges in these fibres may be completely masked by those in other predominant fibres. This and other defects of the technique can undoubtedly be circumvented by using a single isolated fibre of the desired size for the experiments. Since 1942 one of. us (LT.), in collaboration with several co-workers who changed from time to time, has devoted much effort to exploring the physiological properties of various sensory nerve endings with the single fibre technique. By means of the experimental set-up we are using now, it is possible to observe afferent impulses in a single nerve fibre, either myelinated

The effect of inhalation of high and low concentrations of oxygen on the respiration of the premature infant.

Abstract: In a previous investigation (Cross & Warner, 1951) the respiratory adjustments of the normal full-term infant were studied when 100 % oxygen and a mixture of 15 % oxygen and 85 % nitrogen were administered. There appeared to be marked quantitative differences between these results in the newborn and those reported by Dripps & Comroe (1947) in the adult human subject. But whether this was due to a true biological difference, or to a difference between the methods of recording, could not be judged. In this investigation we have studied the reactions of premature infants to the same gas mixtures, using the same apparatus as was used previously, and we have been able to examine whether the trends previously observed were continued in the least mature subjects. The results reported here are mainly concerned with minute volume because, if this figure may be interpreted in terms of Effective Alveolar Ventilation, it represents the single most important factor in external respiration. Tidal air has been reported as an average figure, derived from a measurement of the minute volume and respiration rate for each minute, but these three figures alone afford an incomplete picture of the respiratory behaviour of the baby. There may be not only phasic changes in rate and rhythm, but also frank respiratory irregularity in the sleeping baby, as is illustrated in Cross & Oppe (1952). Without making a complete analysis of these irregularities of rhythm, we have attempted to indicate in a simple quantitative fashion the major modifications of periodic breathing related to the test gases.

The effect of calcium ions on the motor end-plate potentials.

Abstract: Early studies of Locke (1894) revealed that neuromuscular transmission is greatly affected by the ionic composition of the surrounding medium, one of the important factors being the amount of ionized calcium present. Later work has shown that calcium affects the amplitude of the end-plate potential (Eccles, Katz & Kuffler, 1942; Katz, 1942; Coppee, 1943, 1946; Kuffler, 1944). It has been suggested by Feng (1936a, b), Feng & Shen (1937) and Cowan (1940a, b) that the amount of acetylcholine liberated at the motor nerve endings depends on the concentration of calcium ions. This hypothesis, which received support from the work of Harvey & MacIntosh (1940) on the cat's perfused cervical sympathetic ganglion, would also explain the action of calcium on the end-plate potential. In this paper experiments are described which were performed with the purpose of establishing quantitative relationships between calcium concentration and the size of the. end-plate potential, and obtaining additional information on the nature of this effect.

The microphonic activity of the lateral line.

Abstract: One ofthe present authors (de Vries, 1948 a) found three years ago that electrical voltages could be recorded from the lateral lines of fishes when these organs were excited by water currents. This electrical activity is not a nerve response but is identical with the well-known microphonic activity of the cochlea ('Wever and Bray effect') and the other labyrinth organs. The study of the response of the lateral lines is not merely an extension of the important work that has been done on the cochlea. For obvious mechanical and anatomical reasons the lateral line organs are more suited for investigationa of the microphonic activity than the labyrinth organs are; the ontogenetical relation between all these organs implies that the fundamental properties found from the study of one special organ will also be true for the other organs. With respect to this a fundamental problem is the way in which the mechanical stimulus finally gives rise to the excitation of the sense cells. In some previous papers de Vries (1948 a, b, c) suggested that the microphonic activity of the labyrinth organs had a functional meaning. The mechanical energy was supposed to be transformed into electrical energy which could be concentrated on the sense cells in an efficient way. As an extension of the theory it was suggested that this transformation could take place in the tectorial membrane (or in the cupula). Anticipating the results of the present study of the lateral line we might say here that we have disproved this extension. The voltages are not generated by piezo-electric properties of the cupula, but they are related in some way to the stretching of the hairs on the sense cells. The present work also gave information about the functional significance of the microphonic activity.

The level of free choline in plasma

Abstract: Although numerous attempts have been made to estimate the amount of free choline present in blood and tissue fluids, there is little consistency in the results obtained. Table 1 summarizes previous assays of free choline in blood, plasma and serum, and shows a wide scatter of values ranging from l to 75,ug/ml. The effect of quite small doses of choline hydrochloride upon blood pressure (Dale, 1914) and the recent observation by Hutter (1952) that an intravenous injection of as little as 2 mg of choline hydrochloride per kg body weight has an effect upon neuromuscular transmission in the cat, suggest that such a wide range of values is unlikely.

Post-tetanic restoration of neuromuscular transmission blocked by D-tubocurarine.

Abstract: The changes in neuromuscular transmission, which result from repetitive stimulation of the motor nerve, in nerve-muscle preparations partly blocked by D-tubocurarine have been described repeatedly (Boehm, 1894; Boyd, 1932), but little is understood, so far, about their intimate nature. This is partly due to the difficulty of determining the site of the responsible mechanisms, for, so long as the changes in transmission can be detected only by recording from the post-junctional unit, we have no means of telling whether they are due to alterations in the amount of acetylcholine liberated by each nerve impulse, or to changes in the motor end-plates. The experiments here presented were designed to dissociate these variables, by comparing the effects of nerve volleys with those of injected acetylcholine. It will be shown that the early failure of transmission during repetitive stimulation and the subsequent restoration of transmission are both due to changes which take place at the nerve endings, i.e. proximal to the motor end-plates. A preliminary account of these findings has already appeared (Hutter, 1951).

The reflexion of light from the macular and peripheral fundus oculi in man.

Abstract: It has long been disputed whether the yellow pigment of the human macula is present in life or is a post-mortem artifact: most physiologists have taken the former view, but Gullstrand (1906, 1907) and Hartridge (1947) have argued in favour of the latter. Subjective tests on the differences between the spectral sensitivity of the macula as compared with the periphery, as made by Abney (1895), Wald (1945) and others, are all open to the objection that the receptors present in the two fields may differ in their spectral sensitivities or in their contribution to luminosity. A difference in colour between the macular and peripheral parts ofthe fundus oculi is certainly difficult to see by ordinary direct ophthalmoscopy but it is not impossible, and it can be seen more easily if a red-absorbing filter is used. The experiments here described were designed to measure this difference and obtain spectral reflexion curves for macular and peripheral regions of the fundus, using an optical system similar to that employed in retinoscopy to measure the refraction of the eye, but substituting a single oblique glass plate for the perforated retinoscopy mirror in order to avoid the gap in the retinal image caused by the hole, and incidentally (though this has no advantage over the reverse arrangement and was dictated only by mechanical considerations in the apparatus available) interchanging the positions of the light source and the observer.

Visual pigment 467, a photosensitive pigment present in tench retinae.

Abstract: In an investigation of the retinal densities of the scotopic pigments in various animals it was necessary to select for study a representative of the class in which the scotopic response is mediated by visual violet. This class comprises the fresh-water fishes (Wald, 1937a, 1939). Of these, the tench was chosen, since its scotopic sensitivity has been measured (Granit, 1941). Aqueous digitonin extracts of dark adapted tench retinae were prepared for the purpose of estimating the optical density of visual violet in the retina of this fish. On exposing these extracts to light it was found, however, that bleaching was maximal at approximately 520 m,. instead of at 535-540 m,z. as reported by K6ttgen & Abelsdorff (1896) and by Bayliss, Lythgoe & Tansley (1936). As repeated determinations yielded the same unexpected result, it seemed probable that the extracts contained, in addition to visual violet, a photosensitive component absorbing maximally in the blue and not present in the extracts of previous workers. The bleaching of such a component, together with visual violet, could account for the displacement of the maximum photosensitivity from its expected position at 535 m,u. A study of this additional photosensitive component is presented in this paper.

The influence of insulin on the permeability of the blood‐aqueous barrier to glucose

Abstract: Previous studies of the permeability of the blood-aqueous barrier to a series of non-electrolytes have shown that the most important physico-chemical property of the compounds examined in determining their rate of transfer from the plasma into the aqueous humour was their lipoid solubility. It was noted, however (Ross, 1951), that glucose formed an exception to this generalization, for this substance enters the eye at a rate much faster than that of substances of equivalent ether/water partition coefficient: further investigation has therefore been made to elucidate the mechanism of this preferential rate of transfer of glucose across the blood-aqueous barrier. The possibilities appeared to be: first, that glucose underwent a chemical change into a more lipoid-soluble substance before penetrating the cell membrane; this, as is discussed below, is unlikely. Secondly, a special mechanism may exist to accelerate the rate of transfer of glucose across the cell membrane, a process in which insulin may participate. To test this second hypothesis, the rate of penetration of glucose into the eyes of normal rabbits was compared with its rate of penetration in the alloxan-diabetic animal and in the normal animal under the influence of injected insulin.

The permeability of interstitial connective tissue and the nature of the interfibrillary substance

Abstract: This communication is concerned with an experimental study of the permeability of interstitial connective tissue with particular reference to the mode of action of hyaluronidase. It has been suggested that hyaluronidase increases connective tissue permeability by the degradation of a mucopolysaccharide substance present in it (Chain & Duthie, 1940; Duran-Reynals, 1942, 1950). On the other hand, reasons have been given for the belief that the interfibrillary substance, upon which the permeability of the tissue must largely depend, consists predominantly of protein (Day, 1947a, b, 1949). The object of the present study is to resolve this apparent contradiction. The findings to be described suggest that the interfibrillary protein constitutes a net of small mesh in which macromolecules of sufficient size can be impacted, without regard to their precise chemical nature. If the meshes of this net are naturally occupied by molecules of hyaluronic acid, the contradiction is resolved.