THE ELECTRICAL ACTIVATION OF PASSIVE IRON WIRES IN NITRIC ACID

1. The relation between the E. M. F. and the minimal duration of an activating current has been determined for passive iron wires in nitric acid under varying conditions of concentration of acid, duration of recovery period, and presence of surface-action compounds. 2. The characteristic intensity-duration curves resemble those of irritable living tissues with moderate speeds of response to stimulation (with chronaxies of the order of 10 to 30σ). 3. The intensity of the current required for activation, as well as its minimal effective duration for a given intensity, increases rapidly with increase in the concentration of HNO₃. 4. The responsiveness of the iron wire to brief currents is low immediately after activation and returns progressively to the original level during the immediately following period, at first rapidly and then slowly, following a time curve resembling the corresponding curve of living tissues during the relative refractory period. 5. Surface-active compounds decrease reversibly, to a degree dependent on concentration, the responsiveness of iron wires to brief currents. 6. Conditions are described under which the iron wire is activated by the break of an already flowing constant current.     

The Temporal Profiles of Changes in Nerve Excitability Indices in Familial Amyloid Polyneuropathy

Familial amyloid polyneuropathy (FAP) caused by a mutation in transthyretin (TTR) gene is an autosomal dominant inherited disorder. The aim of this study is to explore the pathophysiological mechanism of FAP. We prospectively recruited 12 pauci-symptomatic carriers, 18 patients who harbor a TTR mutation, p.A97S, and two-age matched control groups. Data of nerve excitability test (NET) from ulnar motor and sensory axons were collected.NET study of ulnar motor axons of patients shows increased threshold and rheobase, reduced threshold elevation during hyperpolarizing threshold electrotonus (TE), and increased refractoriness. In sensory nerve studies, there are increased threshold reduction in depolarizing TE, lower slope of recovery and delayed time to overshoot after hyperpolarizing TE, increased refractoriness and superexcitability in recovery cycle. NET profiles obtained from the ulnar nerve of carriers show the increase of threshold and rheobase, whereas no significant threshold changes in hyperpolarizing TE and superexcitability. The regression models demonstrate that the increase of refractoriness and prolonged relative refractory period are correlated to the disease progression from carriers to patients. The marked increase of refractoriness at short-width stimulus suggests a defect in sodium current which may represent an early, pre-symptomatic pathophysiological change in TTR-FAP. Focal disruption of basal lamina and myelin may further increase the internodal capacity, manifested by the lower slope of recovery and delayed time to overshoot after hyperpolarization TE as well as the increase of superexcitability. NET could therefore make a pragmatic tool for monitoring disease progress from the very early stage of TTR-FAP.     

Interpretation of the Repetitive Firing of Nerve Cells

Eccentric cells of Limulus respond with repetitive firing to sustained depolarizing currents. Following stimulation with a step of current, latency is shorter than first interval and later intervals increase progressively. A shock of intensity twice threshold can evoke firing 25 msec. after an impulse. But in the same cell, a current step twice rheobase evokes a second impulse more than 50 msec. after the first, and current intensity must be raised to over five times rheobase to obtain a first interval of about 25 msec. Repetitive firing was evoked by means of trains of shocks. With stimuli of moderate intensity, firing was evoked by only some of the shocks and intervals between successive impulses increased with time. This is ascribed to accumulation of refractoriness with successive impulses. Higher frequencies of firing are obtained with shocks of intensity n x threshold than with constant currents of intensity n x rheobase. It is concluded that prolonged currents depress the processes leading to excitation and that (in the cells studied) repetitive firing is controlled both by the after-effects of firing (refractoriness) and by the depressant effects of sustained stimuli (accommodation). Development of subthreshold "graded activity" is an important process leading to excitation of eccentric cells, but is not the principal factor determining frequency of firing in response to constant currents.     

THE RECOVERY OF TRANSMISSIVITY IN PASSIVE IRON WIRES AS A MODEL OF RECOVERY PROCESSES IN IRRITABLE LIVING SYSTEMS : PART II.

1. Passive iron (steel) wires, when activated after prolonged immersion in nitric acid of 55 to 90 per cent concentration (volumes per cent of HNO₃, specific gravity 1.42) revert spontaneously to the passive state, after a temporary reaction which is transmitted rapidly over the whole length of wire. The duration of this reaction at any region decreases rapidly with increase in the concentration above a certain critical limit of 52 to 54 per cent. In weaker acid (50 per cent and lower) the reaction continues uninterruptedly until all the metal is dissolved. 2. Immediately after this automatic repassivation the wire fails to transmit activation through more than a short distance (1 to 2 cm.); if left undisturbed in the acid it recovers by degrees its power of transmission (as measured by the distance traveled by an activation wave), at first slowly, then more rapidly; eventually, after an interval varying with the concentration of acid and the temperature, the activation wave is transmitted through an indefinite distance as before. 3. The return of complete transmissivity in 55 per cent acid occupies less than a minute (at 20°); in stronger acid it is more gradual, requiring in 90 per cent acid 20 minutes or more. This "complete recovery time" is nearly proportional to the excess of concentration of acid above the limiting value of 53 to 54 per cent. 4. In a given solution of acid the rate of recovery exhibits a temperature coefficient closely similar to that of most chemical reactions at this temperature (3–20°), and also to that of the rate of recovery (refractory period) of irritable living tissues after stimulation (Q ₁₀ = about 3). 5. Two definite phases are distinguishable in the recovery process: (1) the redeposition of the continuous passivating surface layer (of oxide or oxygen compound); and (2) the progressive change of the newly passivated wire from the state of incomplete to that of complete transmissivity. The former phase is of brief duration and is indicated by a sudden change in the electrical potential of the wire, from that of active to that of passive iron; this phase is succeeded by the second and more prolonged period during which the passivating layer undergoes the progressive alteration associated with the recovery of transmissivity. This alteration appears to consist in a progressive thinning of the passivating film until a minimal thickness of (probably 1 molecule) is attained. Further thinning is prevented by local electrochemical oxidation. 6. The phenomena of partial or limited transmission during the second phase of the recovery process show a close correspondence with the phenomena of conduction with decrement in irritable living tissues such as nerve. Other analogies with the behavior of irritable tissues (threshold phenomena, distinction between "local" and "propagated" effects, summation, effects resembling electrotonus) are described.     

Anodal excitation in the Hodgkin-Huxley nerve model.

Computations show that cathodal rheobase increases with temperature from 0 degrees C to 30 degrees C. Anodal rheobase (stimulation at the end of an indefinitely long anodal pulse) also increases with temperature, but goes to infinity at a critical temperature 17.13 degrees C, above which such excitation is impossible. For a stimulus consisting of any step change of current from I0 to I1, a threshold curve of I1 is plotted against I0. As the temperature increases, this curve rises. Its intersection with the horizontal axis, which determines the anodal rheobase, goes to infinity at the critical temperature. This phenomenon is caused by the saturation of the variables m, h, n for strongly hyperpolarized potentials, combined with the relative speeding up of the inhibitory process with increasing temperature. The threshold charge Q in an instantaneous anodal current pulse (of zero duration) goes to infinity at the same temperature, with a similar explanation in terms of threshold curves in the I1 vs. Q plane. The fact that the critical temperature for both cases is the same is generalized by the conjecture that for any anodal current waveform whatever, as its amplitude approaches infinity, the trajectory in the phase space following its cessation approaches the same limiting trajectory. This limiting trajectory changes from suprathreshold to subthreshold at the critical temperature.     

Neuron firing in driven nonlinear integrate-and-fire models

Statistical properties of neuron firing are studied in the framework of a nonlinear leaky integrate-and-fire model that is driven by a slow periodic subthreshold signal. The firing events are characterized by first passage time densities. The experimentally better accessible interspike interval density generally depends on the sojourn times in a refractory state of the neuron. This aspect is not part of the integrate-and-fire model and must be modelled additionally. For a large class of refractory dynamics, a general expression for the interspike interval density is given and further evaluated for the two cases with an instantaneous resetting (i.e. no refractory state) and a refractory state possessing a deterministic lifetime. First passage time densities and interspike interval densities following from the proposed theory compare favorably with precise numerical simulations.     

Effect of the high-voltage electrode polarity and wire preheating on the energy characteristics of electric explosion of fine tungsten wires in vacuum

Results are presented from experiments on the explosion of 30.5-μm tungsten wires at a current density of up to 140 MA/cm² and resistive-heating time of 40–100 ns. The experiments were performed both with and without preheating of wires and at different polarities of the high-voltage electrode. The effect of plasma production at the electrodes on the initiation of breakdown along the exploding wire was investigated by using a frame camera. It is shown that, when the polarity of the high-voltage electrode is positive, breakdown begins with the formation of a bright spot on the wire surface near the cathode, whereas at the negative polarity, breakdown begins with the formation of bright spots on the cathode surface. A comparative analysis of the main characteristics of wire explosions is performed. It is shown that preheating of the conductor increases the resistive-heating time and, accordingly, the energy deposited in the wire core. This effect takes place during explosions of both single wires and wire arrays. The evolution of the state of a metal during the explosion (including melting and evaporation) is studied by one-dimensional simulations by using a semiempirical equation of state describing the properties of tungsten over a wide range of parameters.     

Nanosecond electric explosion of a tungsten wire in different media

The effect of surrounding media of different densities and electric strengths on the heating dynamics of a micron wire during its nanosecond electric explosion is investigated. Tungsten wires with diameters of d = 25–50 μm were exploded in air and water at a current rise time of (dI/dt) ～ 10¹⁰ A/s. The diagnostic complex is described.     

A Model for Mechano-Electrical Feedback Effects on Atrial Flutter Interval Variability

Atrial flutter is a supraventricular arrhythmia, based on a reentrant mechanism mainly confined to the right atrium. Although atrial flutter is considered a regular rhythm, the atrial flutter interval (i.e., the time interval between consecutive atrial activation times) presents a spontaneous beat-to-beat variability, which has been suggested to be related to ventricular contraction and respiration by mechano-electrical feedback. This paper introduces a model to predict atrial activity during atrial flutter, based on the assumption that atrial flutter variability is related to the phase of the reentrant activity in the ventricular and respiratory cycles. Thus, atrial intervals are given as a superimposition of phase-dependent ventricular and respiratory modulations. The model includes a simplified atrioventricular (AV) branch with constant refractoriness and conduction times, which allows the prediction of ventricular activations in a closed-loop with atrial activations. Model predictions are quantitatively compared with real activation series recorded in 12 patients with atrial flutter. The model predicts the time course of both atrial and ventricular time series with a high beat-to-beat agreement, reproducing 96±8% and 86±21% of atrial and ventricular variability, respectively. The model also predicts the existence of phase-locking of atrial flutter intervals during periodic ventricular pacing and such results are observed in patients. These results constitute evidence in favor of mechano-electrical feedback as a major source of cycle length variability during atrial flutter.     

Studies of penetration of the magnetic field into electrically imploded loads in the Angara-5-1 facility

Results are presented from measurements of the distributions of the azimuthal magnetic field in aluminum, copper, molybdenum, tungsten and other wire arrays electrically imploded at currents of up to 3 MA in the Angara-5-1 facility. It is shown that the time during which the magnetic field of the current pulse reaches the array axis depends on the material of the wires or wire coating. The current of the precursor formed on the array axis before the implosion of the main load mass is measured. It is shown that the penetration of the load material with the frozen-in magnetic field into a polymer (agar-agar) foam liner is drastically different from that in the case of a wire array. It is found that the rate of current transfer to the array axis is maximum for tungsten wire arrays. The rates of plasma production during implosion of loads made of different materials are compared.     

Strength-duration curve of conductive spinal cord evoked potentials in cats

Strength-duration curves of the ascending and descending conductive spinal cord potentials (SCEPs) in cats were obtained using constant current stimuli. For the formulation of numeric indices of excitability, the rheobase is defined as the minimal current strength below which response cannot occur even if the current continues, and the chronaxie is defined as the minimal duration of a current required to evoke the potential at twice the rheobase strength. The chronaxies and rheobases were calculated from the constructed strength-duration curves. The purpose of this study is to produce strength-duration curves and to evaluate the utility of chronaxies and rheobases for SCEPs. This study showed the following results: (1) there was a hyperbolic relationship between stimulus strength and stimulus duration at threshold values, similar to that seen in peripheral nerves; (2) the ascending and descending tracts of SCEP were mediated through the same pathway (based on the similar chronaxies and rheobases); (3) following spinal cord compression the chronaxie and rheobase increased significantly (P < 0.05), which is similar to peripheral nerve disturbance. However, the rheobase decreased significantly following slight spinal cord compression (P < 0.05) and systemic cooling (P < 0.01), and the strength-duration curve shifted showing a tendency towards decrease of the galvanic threshold therefore, amplitude augmentation with slight compression and with decrease in temperature seems to contribute to the reduction of the threshold. The strength-duration curve, the chronaxie and the rheobase may be useful in assessing spinal cord function.     

Impulses and Physiological States in Theoretical Models of Nerve Membrane

Van der Pol''s equation for a relaxation oscillator is generalized by the addition of terms to produce a pair of non-linear differential equations with either a stable singular point or a limit cycle. The resulting “BVP model” has two variables of state, representing excitability and refractoriness, and qualitatively resembles Bonhoeffer''s theoretical model for the iron wire model of nerve. This BVP model serves as a simple representative of a class of excitable-oscillatory systems including the Hodgkin-Huxley (HH) model of the squid giant axon. The BVP phase plane can be divided into regions corresponding to the physiological states of nerve fiber (resting, active, refractory, enhanced, depressed, etc.) to form a “physiological state diagram,” with the help of which many physiological phenomena can be summarized. A properly chosen projection from the 4-dimensional HH phase space onto a plane produces a similar diagram which shows the underlying relationship between the two models. Impulse trains occur in the BVP and HH models for a range of constant applied currents which make the singular point representing the resting state unstable.     

Formation and dynamics of plasma layers formed on the foil surface under the action of a high-current pulse

Results are presented from studies of the possibility of using a thin metal foil for recyclable vacuum transmission lines with magnetic insulation in a conceptual fusion reactor based on high-voltage high-current electromagnetic generators. Numerical simulations and experiments in the Angara-5-1 facility were carried out to determine both the threshold for the explosion of a foil heated by a current pulse and the parameters of the plasma layer formed at the foil surface. It was found experimentally that an additional plasma current channel forms on the surface of a 120-μm stainless-steel foil at a linear current density of 0.25–0.5 MA/cm, which corresponds to a magnetic field of 0.3–0.6 MG. For the same conditions, one-dimensional computer simulations of the foil heating were performed in an MHD model by using a wide-range semiempirical equation of state for stainless steel. The calculated threshold for plasma generation on the foil surface is compared with the experimental data. The main parameters of the plasma layer are also calculated at linear current densities of 2–10 MA/cm, which far exceed the threshold current density. The plasma layer parameters as functions of the linear current density are determined for the case of an iron foil.     

Study of the magnetic fields and soft X-ray emission generated in the implosion of double wire arrays

Results are presented from measurements of the azimuthal magnetic field generated during the implosion of double (nested) tungsten wire arrays in the Angara-5-1 facility at currents of ～3 MA. It is found that the inner array affects the current distribution in the interarray space and that there is an optimal mass (an optimal number of wires) of the inner array at which the full width at half-maximum of the soft X-ray pulse (in the photon energy range of >100 eV) is minimal. On the average, double wire arrays provide a better reproductibility, higher power, and shorter duration of the soft X-ray pulse in comparison to single arrays.     

Modulation of adenylate cyclase/cyclic AMP response by thyrotropin and prostaglandin E2 in cultured thyroid cells. 1. Negative regulation.

Isolated porcine thyroid cells, cultured in the presence of thyrotropin (greater than or equal to 0.25 mU/ml) or prostaglandin E2 (greater than or equal to 0.1 micron), showed decreased adenosine 3':5'-monophosphate (cyclic AMP) response to further thyrotropin or prostaglandin E2 stimulation, respectively. Kinetics of the refractory process to thyrotropin and prostaglandin E2 are different: (a) maximal refractoriness to prostaglandin E2 was attained after 2--6 h exposure to prostaglandin E2 while refractoriness to thyrotropin was maximal only after 12--24 h; (b) the degree of refractoriness to prostaglandin E2 was much greater than that to thyrotropin. Refractoriness to thyrotropin or prostaglandin E2 is characterized: by specificity for each thyroid stimulator; by dependence upon the dose of thyrotropin or prostaglandin E2 in culture, e.g. induction of high degree of refractoriness with 0.5 mU/ml thyrotropin (or 1 micron prostaglandin E2), which elicits only a small cyclic AMP increase; by time requirement for induction; by partial effect; by changes of maximum activation of cyclic AMP response; by reversibility. This refractoriness of the cyclic AMP response was not induced by dibutyryl adenosine 3':5'-monophosphate. It was not attributed to increased cyclic AMP-phosphodiesterase activity, but to alterations in the receptor-adenylate cyclase system. Prevention of refractoriness to thyrotropin or prostaglandin E2 by incubation of cells in the presence of actinomycin D, puromycin and cycloheximide suggests that new RNA and protein syntheses are required for the development of the refractory state.     

Action Potentials in Lupinus angustifolius L. Shoots: II. DETERMINATION OF THE STRENGTH-DURATION RELATION AND THE ALL-OR-NOTHING LAW

In Lupinus shoots an electrical stimulus (d.c.) produces a potentialwave analogous to the action potential wave (AP) in stimulatedsimple plant cells or in nerves. The method used (Paszewskiand Zawadzki, 1973a, b) is similar to those applied in neurophysiologyin research on the excitability of nerves. In the present paper the strength-duration relation (Eqn. (1))of the excitation in Lupinusitalic has been used to calculatethe values of the rheobase, chronaxie, and useful time of pulse.The rheobase, as a threshold value of the stimulus, is examinedin terms of the applicability of the all-or-nothing law. The results suggest that the origin and propagation of AP inplants and in nerves may occur in a similar way. The analogybetween the impulse propagation in nerve trunks and in Lupinusshoots is discussed.     

Ultraviolet light and the mitotic cycle in the sea urchin''s egg

The effect of ultraviolet light in delaying certain events in the cell division cycle has been examined. The time to fusion of the egg and sperm nucleus is not affected by doses of ultraviolet that cause considerable delay in other parts of the cycle. The principal delay occurs before anaphase. Between anaphase and cleavage there is only slight delay. The "refractory period" during which the radiation does not delay the immediate cycle of cell division, does not seem to represent complete refractoriness of the mitotic cycle to interference during this period.     

Study of soft X-ray emission from Z-pinches with a complex atomic composition

Results are presented from experimental studies of Z-pinches produced by implosion of aluminum and tungsten cylindrical wire arrays in the Angara-5-1 facility. The electron temperature T _e and density n _e of the high-temperature pinch plasma have been determined by analyzing line emission from multicharged ions. For the same mass and radius of the array and the same number of wires in it, the intensity of line emission of H- and He-like Al ions from an imploded Al + W wire array containing even a small amount of tungsten (7 wt %) is one order of magnitude lower than that from an Al array. As the W content increases, the total soft X-ray (SXR) yield increases, while the duration of the SXR pulse decreases. For the 30% W content in the array, the power and duration of the SXR pulse are nearly the same as those recorded during the implosion of a W array with the same linear mass and radius and the same number of wires. Results are also presented from experiments with nested wire arrays in which the outer and inner shells were made of Al and W wires, respectively. It is found that, in this case, the effect of tungsten on the line emission of aluminum is much weaker than that in experiments with arrays in which tungsten and aluminum wires were placed in the same shell, even if the mass of the inner (tungsten) shell was larger than that of the outer (aluminum) one. At the same time, the inner W shell plays a significant role in the implosion dynamics of a nested wire array, reducing the duration of the SXR pulse and increasing the SXR power.     

Diminution of voltage threshold plays a key role in determining recruitment of oculomotor nucleus motoneurons during postnatal development

The size principle dictates the orderly recruitment of motoneurons (Mns). This principle assumes that Mns of different sizes have a similar voltage threshold, cell size being the crucial property in determining neuronal recruitment. Thus, smaller neurons have higher membrane resistance and require a lower depolarizing current to reach spike threshold. However, the cell size contribution to recruitment in Mns during postnatal development remains unknown. To investigate this subject, rat oculomotor nucleus Mns were intracellularly labeled and their electrophysiological properties recorded in a brain slice preparation. Mns were divided into 2 age groups: neonatal (1-7 postnatal days, n = 14) and adult (20-30 postnatal days, n = 10). The increase in size of Mns led to a decrease in input resistance with a strong linear relationship in both age groups. A well-fitted inverse correlation was also found between input resistance and rheobase in both age groups. However, input resistance versus rheobase did not correlate when data from neonatal and adult Mns were combined in a single group. This lack of correlation is due to the fact that decrease in input resistance of developing Mns did not lead to an increase in rheobase. Indeed, a diminution in rheobase was found, and it was accompanied by an unexpected decrease in voltage threshold. Additionally, the decrease in rheobase co-varied with decrease in voltage threshold in developing Mns. These data support that the size principle governs the recruitment order in neonatal Mns and is maintained in adult Mns of the oculomotor nucleus; but during postnatal development the crucial property in determining recruitment order in these Mns was not the modifications of cell size-input resistance but of voltage threshold.     

GnRH-induced cytosolic calcium oscillations in pituitary gonadotrophs: phase resetting by membrane depolarization.

Cultured rat pituitary gonadotrophs under whole-cell voltage clamp conditions respond to the hypothalamic hormone GnRH with synchronized oscillatory changes in both cytosolic Ca2+ concentration ([Ca2+]i) and [Ca2+]i-activated, apamin-sensitive K+ current (IK(Ca)). We found, and report here for the first time, that in GnRH-stimulated cells a brief depolarizing pulse can elicit a transient [Ca2+]i rise similar to the endogenous cycle. Furthermore, Ca2+ entry during a single depolarizing pulse was found to shift the phase of subsequent endogenous [Ca2+]i oscillations, which thereafter continue to occur at their previous frequency before the pulse. Application of two consecutive depolarizing pulses showed that the size of the [Ca2+]i rise evoked by the second pulse depended on the time lapsed between two consecutive pulses, indicating that each endogenous or evoked [Ca2+]i rise cycle leaves the Ca2+ release mechanism of the gonadotroph in a refractory state. Recovery from this condition can be described by an exponential function of the time lapsed between the pulses (time constant of ca. 1 s). We propose that the underlying mechanism in both refractoriness after endogenous cycles and phase resetting by a brief pulse of Ca2+ entry involves the InsP3 receptor-channel molecule presumed to be located on the cytosolic aspect of the endoplasmic reticulum membrane.