Showing papers in "The Journal of Physiology in 1958"

Temporal and spatial summation in human vision at different background intensities

Abstract: The present experiments were undertaken as part of an investigation of the suggestion made by Rose (1942, 1948) and de Vries (1943) that human visual performance is limited by the inevitable fluctuations in the numbers of quanta absorbed in the retina. In a previous paper (Barlow, 1957) it was shown that this idea (modified by assuming that there is also a weak intrinsic source of noise) leads to theoretical curves which fit experimental determinations of increment threshold made with a short duration small area test stimulus superimposed upon a large uniform adapting field. It was also shown that big changes in the amount of temporal and spatial summation occur when the background intensity is changed, with the result that when thresholds are determined with a long duration large area test stimulus the experimental points deviate from the appropriate theoretical curve and tend to obey the Weber law instead. In following up this finding there were two objectives. The quantum fluctuation hypothesis predicts that the increment threshold intensity should be inversely proportional to the square root ofthe area and duration ofthe stimulus, and the first object was to find whether the occurrence of these laws fitted in with the hypothesis: the results show that the predicted laws of summation do hold over certain ranges, but when they hold the actual values of the thresholds are higher than the theory predicts. The second objective was to determine the parameters oc and r which were introduced in the previous paper; these are the area and time over which quanta absorbed from the background light are liable to be confused with those absorbed from a short duration small area stimulus light, and here the results obtained are disappointing, for one can only derive lower limits to these quantities. On the other hand, the results do show up the complicated interrelations between temporal and spatial summation and background intensity; tentative explanations of these effects, and of the failure to perform up to the quantal fluctuation limit, are put forward. 22 PHYSIO. CXLI

The ionic requirements for the production of action potentials in crustacean muscle fibres.

Abstract: It has been shown that the action potential of the giant axon of the squid arises as a result of a regenerative process which depends on the permeability of its surface membrane to sodium ions being controlled by the membrane potential (Hodgkin & Huxley, 1952 b). From the relationship obtaining between the amplitude of the action potential and the concentration of sodium ions in the surrounding solution, this mode of production ofthe action potential has been inferred to apply also to vertebrate striated muscle (Nastuk & Hodgkin, 1950) and myelinated nerve (Huxley & Stampfli, 1951). It does not, however, apply to crustacean muscle fibres, which, while giving feeble, frequently non-propagating responses in their normal environment, containing a high concentration of sodium, produce large, prolonged action potentials when the sodium is replaced by quaternary ammonium ions (Fatt & Katz, 1953). It has further been observed that some ions (e.g. tetra-n-butylammonium) have an irreversible action: after a muscle has been in a solution containing such ions for a period of time, they can be removed without the muscle losing the ability to produce action potentials, and it is also not necessary for the final solution to contain sodium ions. This observation appears to eliminate the possibility that the role of quaternary ammonium ions in crustacean muscle is the same as that of sodium in other excitable tissues. Nevertheless, an inward transfer of charge across the surface of the fibre is required to displace the potential across the membrane capacity to its value at the peak of the action potential and to balance the outward current carried by potassium and chloride ions; it is clear therefore that there must be either an inward movement of cations or an outward movement of anions. The only cations present in all the solutions in which action potentials could be elicited which could behave in this way were calcium and magnesium. The possibility that an inward movement of calcium ions might be involved in the production

Local activation of striated muscle fibres

Abstract: The question how the excitation process in a muscle fibre reaches the myofibrils themselves has been discussed from time to time (Engelmann, 1873; Retzius, 1881; Tiegs, 1924), but was raised again in an acute form by Hill (1949). There was already at that time much evidence that the feature of excitation which is causally related to contraction was the reduction (or reversal) of the membrane potential (Kuffler, 1946; Katz, 1950); this in itself could not be expected to affect directly any structures more than a few Angstrom units away from the membrane, so that it was necessary to postulate some link by which myofibrils many microns away from the surface were brought into activity. Current flow in the substance of the muscle fibre appeared to be excluded as the causal agent by the experiments of Kuffler (1946; the conclusion has since been confirmed in other experiments by StenKnudsen (1954) and by Watanabe & Ayabe (1956); see also Taylor (1953)). Hill's calculations (1948) showed that the time for diffusion of a hypothetical activating substance, liberated at the surface during the action potential, would be too long to account for the rapidity (Hill, 1949) with which the whole of the contractile material was found to be brought into activity. It therefore seemed that there must be some specific mechanism for this inward spread of activation. The existence of connexions, at the level of the Z line, between adjacent myofibrils, and between superficial myofibrils and the sarcolemma (Enderlein, 1899; Heidenhain, 1911; von Boga, 1937; Draper & Hodge, 1949; Bennett & Porter, 1953), has suggested that this structure may be the route by which the fibrils are activated. The experiments to be described in this paper were begun as an attempt to test this possibility by finding whether contraction could be initiated by depolarizing a small area of membrane lying entirely between the attachments oftwo Z lines. This was found to be impossible in fibres from the frog (Huxley & Taylor, 1955 a, b), in agreement with the

An analysis of the mechanical components in frog's striated muscle.

Abstract: J. Physiol. B. R. Jewell and D. R. Wilkie striated muscle An analysis of the mechanical components in frog's This information is current as of March 19, 2008 JournalsRights@oxon.blackwellpublishing.com reproduced without the permission of Blackwell Publishing: months after publication. No part of this article may be articles are free 12 The Journal of Physiology Online . http://jp.physoc.org/subscriptions/ go to: Physiology Online The Journal of continuously since 1878. To subscribe to The Physiological Society. It has been published is the official journal of The Journal of Physiology Online

The antagonism between Ca and Na ions on the frog's heart.

Abstract: It is well known that replacement of part of the sodium chloride in Ringer's fluid with an osmotically equivalent quantity of sucrose has an effect on the frog's heart which is similar to that of an excess of calcium (Daly & Clark, 1921); in both cases the strength of the beat increases in a striking way. Wilbrandt & Koller (1948) found that these effects are quantitatively related in that the contractile tension is determined by the ratio of the Ca concentration to the square of the Na concentration in Ringer's fluid. This observation has recently been confirmed and extended (Niedergerke & Liittgau, 1957). For example, it was found that heart tissue, depolarized by KCl-rich solutions, can be made to contract and relax, respectively, by reducing and increasing the proportion of Na in the surrounding medium. Moreover, relaxation seems to be brought about specifically by the addition of Na ions since other cations like Li or choline, if used to replace Na, sustained or initiated contracture. These findings could be explained on the assumption that Ca and Na ions compete for some negatively charged substance, probably located near the cell surface, which controls the contractile process. The aim of the present work was to obtain detailed information on this antagonism between Na and Ca, in the hope of finding thereby some clue to the mode of activation of the contractile system.

Membrane currents in isolated frog nerve fibre under voltage clamp conditions

Abstract: With the voltage clamp technique it has been found that the membrane of the squid giant nerve fibre shows a sequence of specific changes in sodium and potassium conductances when the membrane is depolarized (Hodgkin & Huxley, 1952a-d; Hodgkin, Huxley & Katz, 1952). A step depolarization is associated with a rapid transient increase in sodium conductance followed by a slower but lasting increase in potassium conductance. The magnitudes and the rates of change of these permeability changes vary continuously with the membrane potential so that they are larger and more rapid at large cathodal polarizations than at small. The mechanism underlying these permeability changes is mainly unknown, but in further experiments with the voltage clamp technique it was found that the conductance-membrane potential (gNs-V and 9E-V) curves are shifted along the voltage axis when the external calcium concentration is altered (Frankenhaeuser & Hodgkin, 1957). It is not clear to what extent this analysis may be applied to the myelinated nerve fibre. The resting potential is mainly determined by the external potassium concentration, whereas the action potential changes with the external sodium concentration, as it would if the membrane were mainly permeable to sodium at the peak of the action potential (Huxley & Staimpfli, 1951). The effect of changing the external calcium concentration is very much that which is expected on the basis of the squid experiments (Frankenhaeuser, 1957 b). This supports the view that specifit changes in sodium and potassium conductances are the basis for activity in myelinated nerve as they are in squid nerve. On the other hand, from experiments where an action potential is interrupted with an anodal pulse, Tasaki (1956) concludes: 'An unsuccessfu-l attempt was made to interpret these experimental results in terms ofthe sodium theory of nerve excitation', referring to the squid voltage clamp analysis.

Bradykinin formation in human skin as a factor in heat vasodilatation

Abstract: The vasodilatation in the skin of the human forearm produced by indirect heating is not due to the release of vasoconstrictor tone but is the result of an active vasodilator mechanism (Grant & Holing, 1938; Edholm, Fox & Macpherson, 1956a; Roddie, Shepherd & Whelan, 1956). This active vasodilatation might be caused through the excitation of specific vasodilator nerve fibres or by the action of vasodilator substances released from the activated sweat glands. In a discussion with Dr 0. G. Edholm, concerning the mechanism involved, the question was raised whether the polypeptide bradykinin might be produced by the sweat glands and play a similar role in the causation of the cutaneous vasodilatation to that found with the vasodilatation of the activated salivary gland (Hilton & Lewis, 1955 a, b). The present experiments were initiated as a result of this discussion. They show that the vasodilatation which occurs in the human forearm on indirect heating has several features in common with the vasodilatation in the activated salivary gland, and further that sweat gland activity leads to the appearance of the bradykinin-forming enzyme in the sweat and to the formation of bradykinin itself in the skin of the human forearm.

Failure of neuromuscular propagation in rats

Abstract: Many interpretations have been given of the mechanism of muscle fatigue. It is evident that deficient contraction may result from failure at any point in a long chain of events. Various authors disagree as to which link in this chain is the most vulnerable. However, all agree that the nerve trunk is for practical purposes indefatigable, and most authors recognize the occurrence of two main types of peripheral fatigue: fatigue of neuromuscular transmission, and fatigue of the contractile system (del Pozo, 1942; Steiman, 1943; Rosenblueth, 1950; Naess & Storm-Mathisen, 1955). Failure of neuromuscular transmission is commonly ascribed to a deficiency or an excess of transmitter substance (Feng, 1937, 1941; Rosenblueth & Morison, 1937). Other schools of thought may be distinguished. Merton (1954) places all emphasis on fatigue of the contractile mechanism, the occurrence of which, on the other hand, is denied by Ramsey & Street (1941, 1942). Other authors have stressed the importance of fatigue in the central nervous system as the determining factors in fatigue of voluntary contraction (Wailer, 1891; Reid, 1929). In the experiments about to be described, we have studied with intracellular micro-electrodes both in vitro and In situ the mechanism of neuromuscular failure in rats; a number of observations were made which, we believe, may throw some new light on this subject. A preliminary account of some of these experiments has already appeared (Krnjevid & Miledi, 1957).

Intracellular distributions of acetylcholine and choline acetylase.

Abstract: There have been many suggestions that a large part of the acetylcholine (ACh) of nervous tissue is not in a freely diffusible form but instead is bound in some way to the tissue; and that the binding may involve some kind of subcellular particle such as the mitochondrion (Bodian, 1942; Brodkin & Elliott, 1953). From Feldberg's (1945) analysis of the problem it appears that the ester enters the bound state as it is produced: or, as he has phrased it, 'acetylcholine... is synthesized into this linkage'. It may be therefore that within the cell the ester is in close spatial association with the enzyme of synthesis, that is with choline acetylase. The intracellular distribution of this enzyme was studied by Hebb & Smallman (1956) who found that after differential centrifugation of rabbit brain homogenates, 50-70% of the choline acetylase present could be recovered in the granule fraction which included the bulk of the mitochondria; while most of the balance was dissolved enzyme. The present inquiry was directed toward obtaining more information about this distribution and about its relation to the distribution of ACh.

Membrane permeability change during inhibitory transmitter action in crustacean muscle.

Abstract: Impulses in the inhibitory nerve fibre to the limb muscle of the crustacean have been shown to increase the conductance of the post-junctional muscle fibre membrane without there being, in the absence of an applied current, an appreciable change in membrane potential from the resting level (Fatt & Katz, 1953 b). This increase in membrane conductance may be taken to indicate an increase in membrane permeability toward some ions in the neighbourhood, and the fact that the equilibrium potential at which there is no net transfer of charge is close to the resting potential suggests that the ions involved are potassium or chloride, both of which will probably be in a condition of equilibrium across the resting membrane. The experiments reported in this paper were designed to establish toward which of these two species of ions the permeability is increased. The procedure was to examine the effect on the inhibitory response of variation in the concentrations of K+ and Clions in the solution bathing the muscle. A subsidiary problem was to determine the action of y-aminobutyric acid on the membrane properties.

Studies on the internal pH of large muscle and nerve fibres.

Abstract: In a previous paper (Caldwell, 1954) a form of the glass electrode suitable for insertion into large muscle and nerve fibres was described, together with an account of some determinations with the electrode of the internal pH of the leg muscle fibres of the crab Carcinus maenas. In this paper more extensive studies of internal pH are presented. These comprise an investigation of the internal pH of the leg muscle fibres of C. maenas under a wide variety of conditions, and similar but less complete investigations of the internal pH of the leg muscle fibres of the crab Maia squinado, and of the giant axon of the squid Loligo forbesi. One of the main purposes of these studies has been to find out whether the pH difference between the inside of the fibres and their surroundings varies in the manner predicted by the Donnan equilibrium theory (Donnan, 1911), according to which the following relationship should hold (at 20° C) for a membrane permeable to H+ ions: Internal pH-pH of surroundings =log10 (H+ activity in surroundings) (Internal H+ activity) Resting potential (in mV) 58*17 (Note that this formulation differs from that given in the previous paper in that the resting potential is regarded here as being a negative quantity under normal conditions.) A preliminary account of some of the work described in this paper was given to the 3rd International Congress of Biochemistry (Caldwell, 1955).

A study on the mechanism of impulse transmission across the giant synapse of the squid

Abstract: The structure of the axo-axonal synapses in the stellate ganglion of the squid has been investigated by several anatomists and physiologists. In 1939, Young published the results of his gross anatomical and histological studies on the synapses in this ganglion. He showed that a large axon (about 100 ,u in diameter) which has its origin in a higher ganglion divides in this ganglion into about ten smaller branches. Each of these branches ends blindly on the surface of one of the motor giant axons, making a synaptic junction. Among these synapses in the stellate ganglion, the largest one is the junction between the presynaptic axon and the so-called squid giant axon which has been used widely for electrophysiological studies of the excitable membrane. Robertson (1953) carried out electron microscope studies on this synapse and found that, in the region where the two axons make contact, there are a number of axoplasmic processes which are the extensions of the post-synaptic axon. These processes end in close apposition with the axoplasm of the presynaptic axon. The physiological investigation of this synapse was started also by Young (1939). He found that transmission of impulses through this synapse is unidirectional and is readily blocked on repetitive stimulation of the presynaptic axon. In 1949, Bullock found that a synaptic potential, which resembles in many respects the end-plate potential of the curarized neuromuscular junction (Schafer & G6pfert, 1937; Eccles & O'Connor, 1939; Kuffler, 1942; Fatt & Katz, 1951), can be recorded in the vicinity of this synapse. Recently, Bullock & Hagiwara (1957) examined the time course of the synaptic potential and the synaptic delay with intracellular micro-electrodes. In the present work, an attempt is made to elucidate the mechanism of impulse transmission across this giant synapse by using various techniques

The effects of stimulation of the carotid body chemoreceptors on heart rate in the dog.

Abstract: It is well known that hypoxia causes tachycardia, but there is no general agreement as to the mechanism of this effect. Some workers have assumed it to be the result of a reflex arising from stimulation of the carotid body and aortic arch chemoreceptors (Asmussen & Chiodi, 1941; von Euler & Liljestrand, 1942; Whitehorn, Edelmann & Hitchcock, 1946; Dripps & Comroe, 1947; Alveryd & Brody, 1948), despite there being a number of conflicting reports of the effects of stimulation of the chemoreceptors on heart rate. Stimulation of the carotid bodies by various drugs injected into the common carotid artery of spontaneously breathing dogs caused bradycardia (Heymans, Bouckaert & Dautrebande, 1931 a, b; Heymans, Bouckaert, von Euler & Dautrebande, 1932; Heymans, Bouckaert, Farber & Hsu, 1936; Comroe & Schmidt, 1938; Heymans & Bouckaert, 1941), but perfusion of the carotid sinus region using Ringer's solution with either a high CO2 content or a low pH resulted in tachyeardia (Heymans, Bouckaert & Dautrebande, 1930; Heymans, Bouckaert & Samaan, 1935). More recently, Bernthal, Greene & Revzin (1951) excited the carotid bodies by hypoxic blood and found variable effects on heart rate. In every case chemoreceptor stimulation, whether by drugs, Ringer's solution or hypoxic blood, caused reflex hyperpnoea. On the other hand, in dogs in which the rate and depth of respiration were controlled by a pump, stimulation of the carotid bodies by either hypoxic or venous blood invariably caused bradycardia (Bernthal et al. 1951; Daly & Daly, 1957). In the cat Landgren & Neil (1952) found that stimulation of chemoreceptors by local application of various drugs to the carotid bodies invariably caused hyperpnoea, hypertension and tachycardia. In subsequent experiments, in which carotid body perfusion techniques were used, Neil (1956) showed that the tachycardia which occurs in systemic hypoxia was not the result of stimulation of the carotid body chemoreceptors.

The excitation of Renshaw cells by pharmacological agents applied electrophoretically.

Abstract: It has been reported that a group of cells lying within the ventral horn of the lumbar segments of the spinal cord of the cat are normally discharged by the release of acetylcholine from the terminals of the motor axon collaterals (Eccles, Fatt & Koketsu, 1954; Eccles, Eccles & Fatt, 1956). These cells, the Renshaw cells, in turn inhibit adjacent motoneurones. Some of the pharmacological properties of these pathways have already been investigated (Curtis, Eccles & Eccles, 1957). The anomalous behaviour of these cells when tested with certain drugs, specifically acting on peripheral cholinergic synapses, given either intravenously or intra-arterially, has suggested that they are surrounded by at least two diffusional barriers. In order to investigate these barriers more closely, methods have been devised by which drugs can be applied directly from a micro-electrode in the vicinity of the cell. These methods have been used in an investigation of the neuromuscular junction (del Castillo & Katz, 1955; 1957a-c). METHODS

The effects of adrenaline, noradrenaline and isoprenaline on skeletal muscle contractions in the cat

Abstract: Adrenaline, noradrenaline and other sympathomimetic amines have been shown to increase the maximal twitch tension of unfatigued skeletal muscles (Oliver & Schaefer, 1895; Gruber, 1922a, b; Goffart & Brown, 1947; West & Zaimis, 1949; Brown, Goffart & Vianna Dias, 1950; Goffart & Ritchie, 1952; Huidobro, Cubillos & Eyzaguirre, 1952; Goffart, 1952, 1954; Montagu, 1955). This response, however, is not characteristic of all skeletal muscles. In fact the present experiments show that, in the cat, slow contracting muscles such as the soleus respond in a completely opposite way. A short account of the results has already been published (Bowman & Zaimis, 1955).

The electrophysiological identification of single nerve fibres, with particular reference to the slowest-conducting vagal afferent fibres in the cat.

Abstract: Although there are many unmyelinated afferent axons in the peripheral nerves of mammals there is very little known either about their behaviour or about the receptors with which they are connected. Myelinated fibres, on the other hand, have frequently been studied as single units. This situation is due to the difficulty of isolating the unmyelinated fibres as single units for electrophysiological recording. Activity in unmyelinated afferent fibres has been recorded in multifibre preparations, notably by Zotterman (1939) and Maruhashi, Mizuguchi & Tasaki (1952). Only occasionally did these authors succeed in analysing activity in individual fibres. Douglas & Ritchie (1957a, b) have recently succeeded in detecting C fibre activity in whole nerves. Because of this lack of information about individual unmyelinated fibres it was decided to follow up the observation (Iggo, 1956b) that afferent fibres with conduction velocities as low as 1-3 m/sec could be isolated as single units from the cervical vagus of the goat. In addition to measurements of conduction velocity other tests were used in an attempt to decide whether the fibres were unmyelinated. New methods for identifying single fibres in a multifibre strand are described. With the aid of these methods and by refinements of the usual dissection methods very slowly conducting fibres have now been isolated in the cat. Evidence is presented for the conclusion that most of these fibres were probably unmyelinated. Preliminary reports have already appeared (Iggo, 1956 b, 1957 c). The gastric and intestinal receptors for which these figures were the centripetal axons are described elsewhere (Iggo, 1957a, b).

Effects of drugs on depolarized plain muscle

Abstract: It has been briefly reported (Evans & Schild, 1957) that mammalian plain muscle retains its ability to contract in response to drugs when suspended in Ringer's solution in which the sodium ions have been replaced by potassium ions. This observation suggested that drugs can affect the contractile elements of plain muscle by a mechanism which is not mediated by membrane depolarization. Since it is generally considered that a membrane potential change is an essential step in setting off the contractile process both in striated (Huxley, 1957) and smooth (Csapo, 1954) muscle, these findings were considered to warrant further study. In this paper the effects upon their reactions to drugs of immersing smooth muscles in 'potassium-Ringer' are now described more fully, and their responses to electrical and to mechanical stimulation are also reported. To test whether smooth muscle cells are in fact completely depolarized by the external application of potassium, membrane potentials have been recorded with intracellular micro-electrodes.

A method for studying the effects of ions and drugs on the resting and action potentials in smooth muscle with external electrodes.

Abstract: A number of papers have dealt with the effects of drugs on the rate and height of action potentials in smooth muscle (cf. Bozler, 1948; Biilbring, 1956), but there are relatively few descriptions of changes in the resting potential. This is probably because an external electrode technique has not been available and resting potential measurements with internal electrodes are difficult to make, owing to the small size and spontaneous motility of the smooth muscle fibres (Biilbring, 1955). A few years ago Staimpfli (1954) described a relatively simple method for measuring the full value of the resting potential with external electrodes. His method is based on the theoretical calculation that the full value of the membrane potential can be measured with external electrodes on a core conductor, when the short-circuiting is negligible (Hodgkin & Rushton, 1946). Staimpfli obtained this condition by increasing the outside resistance of the preparation in the interpolar region by replacing most of the ions in the interstitial fluid with a nearly ion-free sucrose solution. This method has so far been applied to bundles of myelinated nerve fibres (Stampfli & Straub, 1954), and to non-medullated fibres (Ritchie & Straub, 1956, 1957), where action potentials were also recorded. The present paper deals with the application of this technique to smooth muscle.

Membrane potentials recorded with high‐resistance micro‐electrodes; and the effects of changes in ionic environment on the electrical and mechanical activity of the smooth muscle of the taenia coli of the guinea‐pig

Abstract: Membrane potentials of the rhythmically active smooth muscle of the taenia coli of the guinea-pig have been described previously by Biilbring (1954, 1955, 1956, 1957). The effects of changes in ionic environment on the mechanical activity of intestinal muscle (rate of spontaneous contractions and tonus) have been studied by Evans (1926), Magee & Reid (1927), Vogt (1943) and Ambache (1946). Less is known of the electrical activity under these conditions. Effects of changes in NaCl concentration have been described by Holman (1957a) and a brief account has been given of observations when the KCI concentration was varied (Holman, 1957b). Burnstock & Straub (1958) studied the effects of changes in the concentration of K, Ca and Cl ions on the resting potential of strips of smooth muscle from the gut of various species, using the sucrosegap method. In general their results were similar to those found with intracellular recordings. In the present experiments relatively high resistance capillary microelectrodes have been used to record membrane potentials in an attempt to minimize the degree ofcell injury. Some aspects of the normal activity recorded with these electrodes will be described, together with the effects of variation in the concentration of K, Cl and Ca ions. Some further experiments have been carried out in solutions containing very low concentrations of Na ions.