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.     

Activation of passive iron as a model for the excitation of nerve

The activation by cathodic polarization of passive iron in concentrated nitric acid (d = 1.4) has been investigated. 1. For short current pulses (1 msec. or less) a transient activation occurs when the product of current density and time exceeds a certain value. This limiting value is here designated as the "threshold." It is of the order of magnitude of 200 x 10(-6) coulomb/cm.(2). 2. After activation and repassivation the threshold is temporarily several times higher than before. This "refractory state" is due to the presence of nitrous acid and of oxide layers. The return of the threshold to normal values occurs in seconds or minutes, depending on the variety of iron wire. 3. Immediately after a subthreshold current pulse the threshold is reduced (summation). However, if the second pulse occurs a certain interval of time after the first the wire exhibits a certain degree of refractoriness (Gildemeister effect). 4. Oscillographic measurements reveal the existence of a latent period between the application of the stimulating pulse and the establishment of the active state. The duration of this latent period depends on the strength of the current pulse. 5. There exists a minimum current density (rheobase) below which no activation occurs however long the current is applied. Depending on the variety of iron used this current density varies between about 1 and 10 ma./cm.(2). To produce activation a current of rheobasic strength does not have to be applied for an infinite time but only for about 100 msec. (maximum utilization time). Activation becomes manifest some time after termination of the activating pulse. 6. With currents of slowly increasing strength it is possible to reach current strengths several times higher than rheobase without obtaining activation (accomodation). Accomodation to a large extent depends on the variety of iron used. Details are given for currents increasing with a time constant of 0.5 second. 7. Potential measurements on wires in the refractory state show the existence of after potentials. Wires in the refractory state which are cathodically polarized show peculiar oscillograms. Both types of experiments point to the formation of nitrous acid as an essential element in the course of events. 8. With current densities only slightly above rheobase all wires exhibit simple activations only. With higher current densities certain types of wires exhibit periodic activations. The range of current densities in which such periodic activations occur varies with the type of wire. The lower limit is sometimes quite close to the rheobase. 9. A theory of periodic activations is presented which is modelled on the theory of self-excitatory electrical oscillations. As variables describing the state of the wire, the "degree of activation" and the "degree of refractoriness" are introduced. In the physicochemical system an autocatalytic process corresponds to the "falling characteristic" of electrical oscillations. The theory leads to a rational view of the interrelations between threshold, rheobase, accomodafion, refractoriness, and rhythm. The phenomena of conduction are not discussed here but their relation to the theory is briefly touched upon.     

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.     

Laser radiation scattering from the wires and fibers of imploding arrays on the Angara-5-1 facility

A method is developed for measurements of laser radiation scattering by wires and fibers in different types of imploding arrays in the initial stage of plasma production at discharge currents per wire of up to 2 kA for aluminum arrays and up to 8 kA for tungsten arrays. The experiments were carried out on the Angara-5-1 facility at a current density in the wires of 10⁸ A/cm² and current growth rate of ～10¹³ A/s. It is found that the indicatrix of laser radiation reflected from the wires (fibers) in cylindrical and conical arrays is modified at currents of 0.1–10 kA per wire (fiber). The experimental data on the reflection and scattering of laser radiation from wires and fibers are compared with the results of numerical simulations of their electric explosion in vacuum. It is proposed that the change in the reflection indicatrix of laser radiation is caused by the onset of thermal instabilities. The typical size of density and temperature inhomogeneities on the wire surface is in a range of 10–20 μm, which probably results in a transition from specular to diffuse reflection of laser radiation. A simultaneous abrupt (over 2–3 ns) reduction in the reflection intensity from several wires of an array indicates a homogeneous distribution of the discharge current over the irradiated wires. This closes the issue of the quality of the contact between the wires and the electrodes. The obtained experimental information is of considerable importance for the development of numerical codes for simulations of the implosion of wire arrays and the refinement of the wire parameters in the initial stage of plasma production.     

Study of the implosion of wire arrays at the PF-3 facility

Results of experiments on the compression of tungsten wire arrays by the plasma current sheath (PCS) of the PF-3 facility at currents of up to 2 MA are presented. The efficiency of current transportation to the wire array and switching-over of the discharge current to the array were studied. Information on the penetration of the magnetic field into the wire array obtained using microprobes made it possible to compare the obtained experimental data with the results of magnetic field measurements carried out at other high-power electrophysical devices. The intensity of plasma production from tungsten wires under the action of the plasma focus PCS is estimated. The experimental results are tested against the existing models of wire array implosion with prolonged plasma production.     

THE CONDITIONS OF RECOVERY OF TRANSMISSIVITY OF NEWLY REPASSIVATED IRON WIRES IN NITRIC ACID

1. Passive steel wires were activated in a bath (Bath A) containing 70 v. per cent HNO₃ (in which they undergo prompt repassivation), and immediately transferred to a second bath (Bath B) containing HNO₃ of a concentration varying in different experiments. After varying intervals in this bath they were transferred while still passive to a third bath (Bath C) containing strong HNO₃ (70 or 100 v. per cent) and there immediately activated. 2. During the immersion in Bath B the wires progressively recover their ability to transmit activation waves in strong HNO₃. The measure of this recovery is the distance travelled by the activation waves in Bath C after the varying times of exposure in Bath B. Transmissivity as thus measured is at first incomplete (decremental) and later becomes complete. The minimal exposures in Bath B required to render wires completely transmissive in the strong acid of Bath C were determined for concentrations of HNO₃ between 10 and 100 v. per cent. With 100 v. per cent HNO₃ in Bath C, these exposures range from 40 minutes or more in 15 v. per cent to 10 minutes in 100 v. per cent HNO₃ (temperature 19–20° in all baths). 3. The time required for complete recovery varies inversely with the concentration of the acid in the recovery bath (Bath B), but increases rapidly with the concentration of the acid in the testing bath (Bath C). Hence at a time when a wire has recovered just sufficiently to transmit non-decrementally in a given strong acid (e.g., 70 v. per cent) it still transmits decrementally in a stronger acid. Complete recovery for transmission in 100 v. per cent HNO₃ requires about twice as long as for 70 v. per cent HNO₃. In HNO₃ of 50 v. per cent and less decremental transmission does not occur. 4. The indications are that recovery is an effect of the progressive solvent action of the external acid on the passivating oxide film, which at its first deposition appears to be relatively thick and hence resistant to electrochemical reduction. The final stage of recovery, when electrical sensitivity and speed of transmission are maximal, would on this hypothesis correspond to minimal thickness, possibly monomolecular. 5. The rate of recovery in Bath B is not far from proportional to the concentration of HNO₃ in the more dilute solutions, but in the higher, especially the strongly passivating, concentrations (70 to 100 v. per cent) the rate becomes appreciably slower than proportional, apparently because of the intense oxidizing action of these solutions, which reinforces the oxide sheet and retards the thinning process. 6. The bearing of these observations on the problem of the conditions of recovery in irritable living tissues (such as nerve) during the absolute and relative refractory periods is briefly discussed.     

Study of the implosion characteristics of quasi-spherical wire arrays on the Angara-5-1 facility at currents of up to 4 MA

Results are presented from experimental studies of the spatial distribution of the density of matter in the central part of the discharge gap and the formation of the temporal profile of the X-ray power in the course of implosion of quasi-spherical wire arrays at discharge currents of up to 4 MA. The spatial distribution of the X-ray intensity in the central part of the discharge gap and the temporal profile of the X-ray power are used as implosion characteristics of quasi-spherical wire arrays. The quasi-spherical arrays were formed by the radial stretching of unstrained wires of initially cylindrical and conical wire arrays under the action of the electrostatic field. The temporal profile of the output X-ray pulse in the photon energy range of 0.1–1 keV is shown to depend on both the geometrical parameters of the quasi-spherical array and the longitudinal distribution of its mass. It is found that a 40% increase in the wire mass due to deposition of an additional mass in the equatorial region of a quasi-spherical array leads to a 15% increase in the average current radius of the pinch and a 30% decrease in the X-ray yield. Experiments with quasi-spherical arrays made of kapron fibers with deposited Al and Bi conducting layers were also carried out. It is demonstrated that application of such arrays makes it possible to control the profile and duration of the generated X-ray pulse by varying the mass, material, and location of the deposited layer. It is found that deposition of an additional mass in the form of a thin Bi stripe on tungsten wires near the cathode end of the array allows one to mitigate the influence of the cathode zipper effect on the pinch compression and formation of the X-ray pulse in tungsten arrays.     

Squid giant axons. A model for the neuron soma?

Insertion of electrically floating wires along the axis of a squid giant axon produces an apparent increase in diameter in the region where the wire surface has been treated to give it a low resistance. The shape of action potentials propagating into this region depend upon the surface resistance (and the length) of the wire. As this segment's internal resistance is lowered by reducing the wire's surface resistance, the following characteristic sequence of changes in the action potential is seen at the transition region: (a) the duration increases; (b) two peaks develop, the first one generated in the normal axon region and the second one generated later in the axial wire region, and; (c) blockage occurs (for a very low resistance wire). Action potentials recorded at the membrane region near the tip of the axial wire in (b) resemble those recorded at the initial segment of neurons upon antidromic invasions. Squid axon action potentials propagated from a normal region into that containing the low resistance wire also resemble antidromic invasions recorded in neuron somas. Hyperpolarizing current pulses applied through the wire act as if the wire surface resistance was momentarily reduced. For example, the two components of the action potential recorded at the axial wire membrane region noted in (b) can be sequentially blocked by the application of increasing hyperpolarizing current through the wire. Similar effects are seen when hyperpolarizing currents are injected into motoneuron somas. It is concluded that the geometrical properties of the junction of a neuron axon with its soma may be in themselves sufficient to determine the shape of the action potentials usually recorded by microelectrodes.     

Response of Human Thalamic Neurons to High-Frequency Stimulation

Thalamic deep brain stimulation (DBS) is an effective treatment for tremor, but the mechanisms of action remain unclear. Previous studies of human thalamic neurons to noted transient rebound bursting activity followed by prolonged inhibition after cessation of high frequency extracellular stimulation, and the present study sought to identify the mechanisms underlying this response. Recordings from 13 thalamic neurons exhibiting low threshold spike (LTS) bursting to brief periods of extracellular stimulation were made during surgeries to implant DBS leads in 6 subjects with Parkinson''s disease. The response immediately after cessation of stimulation included a short epoch of burst activity, followed by a prolonged period of silence before a return to LTS bursting. A computational model of a population of thalamocortical relay neurons and presynaptic axons terminating on the neurons was used to identify cellular mechanisms of the observed responses. The model included the actions of neuromodulators through inhibition of a non-pertussis toxin sensitive K⁺ current (I_KL), activation of a pertussis toxin sensitive K⁺ current (I_KG), and a shift in the activation curve of the hyperpolarization-activated cation current (I_h). The model replicated well the measured responses, and the prolonged inhibition was associated most strongly with changes in I_KG while modulation of I_KL or I_h had minimal effects on post-stimulus inhibition suggesting that neuromodulators released in response to high frequency stimulation are responsible for mediating the post-stimulation bursting and subsequent long duration silence of thalamic neurons. The modeling also indicated that the axons of the model neurons responded robustly to suprathreshold stimulation despite the inhibitory effects on the soma. The findings suggest that during DBS the axons of thalamocortical neurons are activated while the cell bodies are inhibited thus blocking the transmission of pathological signals through the network and replacing them with high frequency regular firing.     

Subtypes of dorsal root ganglion neurons based on different inward currents as measured by whole-cell voltage clamp

Electrophysiological and pharmacological properties distinguished subtypes of adult mammalian dorsal root ganglion neurons (DRGn) in monolayer dissociated cell culture. By analogy of action potential waveform and duration, neurons with short duration (SDn) and long duration (LDn) action potentials resembled functionally distinct subtypes of DRGn in intact ganglia. Patch clamp and conventional intracellular recording techniques were combined here to elucidate differences in the ionic basis of excitability of subtypes of DRGn in vitro. Both SDn and LDn were quiescent at the resting potential. Action potentials of SDn were brief (less than 2 msec), sensitive to tetrodotoxin (TTX, 5-10 nM), exhibited damped firing during long depolarizations, and did not respond to algesic agents applied by pressure ejection. Action potentials of LDn were 2-6 msec in duration, persisted in 30 microM TTX, and fired repetitively during depolarizing current pulses or exposure to algesic agents (e.g., capsaicin, histamine and bradykinin). Whole-cell recordings from freshly dissociated neurons revealed two inward sodium currents (INa; variable with changes in sodium but not calcium concentration in the superfusate) in various proportions: a rapidly activating and inactivating, TTX-sensitive current; and, a slower, TTX (30 microM)-resistant INa. Large neurons, presumable SDn, had predominantly TTX-sensitive current and little TTX-resistant current. The predominant inward current of small neurons, presumably LDn, was TTX-resistant with a smaller TTX-sensitive component. By analogy to findings from intact ganglia, these results suggest that fundamentally different ionic currents controlling excitability of subtypes of DRGn in vitro may contribute to functional differences between subtypes of neurons in situ.     

Symmetric multilayer megampere X-pinch

Raising the power of X-ray emission from an X-pinch by increasing the pinch current to the megampere level requires the corresponding increase in the initial linear mass of the load. This can be achieved by increasing either the number of wires or their diameter. In both cases, special measures should be undertaken to prevent the formation of a complicated configuration with an uncontrolled spatial structure in the region of wire crossing, because such a structure breaks the symmetry of the neck formed in the crossing region, destabilizes plasma formation, and degrades X-ray generation. To improve the symmetry of the wire crossing region, X-pinch configurations with a regular multilayer arrangement of wires in this region were proposed and implemented. The results of experiments with various symmetric X-pinch configurations on the COBRA facility at currents of ∼1MA are presented. It is shown that an X-pinch with a symmetric crossing region consisting of several layers of wires made of different materials can be successfully used in megampere facilities. The most efficient combinations of wires in symmetric multilayer X-pinches are found in which only one hot spot forms and that are characterized by a high and stable soft X-ray yield.     

Time dependence of the calcium-activated potassium current.

We investigated the dependence of the kinetics of the Ca2+-activated K+ current of the molluscan neuron soma upon membrane potential. The K+ current was activated by intracellular Ca2+ ion injection in neurons with blocked inward Na+ and Ca2+ currents. The difference between currents was measured with brief pulses (less than 100 ms) before and immediately after Ca2+ injection and was used as the Ca2+ activated K+ current at difference membrane potentials. The results in normal (10 mM) and in high (200 nM) external K+ show that the time-course of the Ca2+-activated K+ current depends upon membrane voltage and that the current activates more rapidly with membrane depolarization.     

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.     

Electrophysiological investigation of the properties of the electroreceptors (ampullae of Lorenzini) in Black Sea rays

Responses of electroreceptors (ampullae of Lorenzini) in Black Sea rays to electrical stimuli were recorded in vivo as spike activity of single nerve fibers. Depending on their functional properties the fibers could be divided into silent, those with regular activity (10–15 spikes/sec) and those with grouped activity. Electrical stimuli evoked a tonic response with a varied degree of adaptation in the nerve fibers. The threshold currents were between 10^?10 and 10^?11 A/mm². The minimal latent period of the on-responses to pulses of current of maximal intensity was 15–40 msec, whereas that of the off-responses was 15–200 msec. The effect of intensity, duration, and polarity of the stimuli on the responses of the receptors and the adaptation of the electroreceptors during application of a steady current were investigated. The properties of the ampullae of Lorenzini were compared with those of other types of electroreceptors.     

RESEMBLANCES BETWEEN THE ELECTROMOTOR VARIATIONS OF RHYTHMICALLY REACTING LIVING AND NON-LIVING SYSTEMS

1. The electromotor variations of pure iron wires, arranged to react rhythmically with nitric acid, are recorded and described. 2. Resemblances between these variations and those of rhythmically reacting living tissues (especially the heart) are pointed out and discussed.     

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.     

Sperm-induced currents at fertilization in sea urchin eggs injected with EGTA and neomycin.

Membrane currents were measured in single voltage-clamped sea urchin eggs (Lytechinus pictus and Lytechinus variegatus) that were injected with either EGTA or neomycin and inseminated. Although egg activation and the fertilization calcium wave were prevented by injection of either of these compounds, sperm attached and still elicited inward currents. Sperm-induced currents in EGTA-injected eggs had an abrupt onset, quickly reached a maximum, and then slowly declined in amplitude. Sperm incorporation occurred readily in EGTA-injected eggs. Similar results were obtained with another calcium chelator, BAPTA. In neomycin-injected eggs, sperm-induced currents generally had an abrupt onset and, in contrast to EGTA-injected eggs, the currents usually cut off rapidly. Sperm failed to enter the neomycin-injected eggs and the duration of sperm-induced currents in neomycin-injected eggs was markedly dependent upon the voltage-clamp holding potential, with shorter duration currents occurring at -70 than at -20 mV. The lability of the initial interaction between sperm and egg at negative holding potentials may explain why activation often fails when the egg membrane is voltage clamped at these potentials (Lynn et al., Dev. Biol. 128, 305-323, 1988).     

Characterization of two distinct depolarization-activated K+ currents in isolated adult rat ventricular myocytes

Depolarization-activated outward K+ currents in isolated adult rat ventricular myocytes were characterized using the whole-cell variation of the patch-clamp recording technique. During brief depolarizations to potentials positive to -40 mV, Ca(2+)-independent outward K+ currents in these cells rise to a transient peak, followed by a slower decay to an apparent plateau. The analyses completed here reveal that the observed outward current waveforms result from the activation of two kinetically distinct voltage-dependent K+ currents: one that activates and inactivates rapidly, and one that activates and inactivates slowly, on membrane depolarization. These currents are referred to here as Ito (transient outward) and IK (delayed rectifier), respectively, because their properties are similar (although not identical) to these K+ current types in other cells. Although the voltage dependences of Ito and IK activation are similar, Ito activates approximately 10-fold and inactivates approximately 30-fold more rapidly than IK at all test potentials. In the composite current waveforms measured during brief depolarizations, therefore, the peak current predominantly reflects Ito, whereas IK is the primary determinant of the plateau. There are also marked differences in the voltage dependences of steady-state inactivation of these two K+ currents: IK undergoes steady-state inactivation at all potentials positive to -120 mV, and is 50% inactivated at -69 mV; Ito, in contrast, is insensitive to steady-state inactivation at membrane potentials negative to -50 mV. In addition, Ito recovers from steady-state inactivation faster than IK: at -90 mV, for example, approximately 70% recovery from the inactivation produced at -20 mV is observed within 20 ms for Ito; IK recovers approximately 25-fold more slowly. The pharmacological properties of Ito and IK are also distinct: 4-aminopyridine preferentially attenuates Ito, and tetraethylammonium suppresses predominantly IK. The voltage- and time-dependent properties of these currents are interpreted here in terms of a model in which Ito underlies the initial, rapid repolarization phase of the action potential (AP), and IK is responsible for the slower phase of AP repolarization back to the resting membrane potential, in adult rat ventricular myocytes.     

Mechanical signal influence on mesenchymal stem cell fate is enhanced by incorporation of refractory periods into the loading regimen

Mechanical signals of both low and high intensity are inhibitory to fat and anabolic to bone in vivo, and have been shown to directly affect mesenchymal stem cell pools from which fat and bone precursors emerge. To identify an idealized mechanical regimen which can regulate MSC fate, low intensity vibration (LIV; <10 microstrain, 90 Hz) and high magnitude strain (HMS; 20,000 microstrain, 0.17 Hz) were examined in MSC undergoing adipogenesis. Two x twenty minute bouts of either LIV or HMS suppressed adipogenesis when there was at least a 1h refractory period between bouts; this effect was enhanced when the rest period was extended to 3h. Mechanical efficacy to inhibit adipogenesis increased with additional loading bouts if a refractory period was incorporated. Mechanical suppression of adipogenesis with LIV involved inhibition of GSK3β with subsequent activation of β-catenin as has been shown for HMS. These data indicate that mechanical biasing of MSC lineage selection is more dependent on event scheduling than on load magnitude or duration. As such, a full day of rest should not be required to "reset" the mechanical responsiveness of MSCs, and suggests that incorporating several brief mechanical challenges within a 24h period may improve salutary endpoints in vivo. That two diverse mechanical inputs are enhanced by repetition after a refractory period suggests that rapid cellular adaptation can be targeted.     

Light-induced changes of sensitivity in Limulus ventral photoreceptors

The responses of Limulus ventral photoreceptors to brief test flashes and to longer adapting lights were measured under voltage clamp conditions. When the cell was dark adapted, there was a range of energy of the test flashes over which the peak amplitude of the responses (light-induced currents) was directly proportional to the flash energy. This was also true when test flashes were superposed on adapting stimuli but the proportionality constant (termed peak currently/photon) was reduced. The peak current/photon was attenuated more by brighter adapting stimuli than by less bright adapting stimuli. The peak current/photon is a measure of the sensitivity of the conductance-increase mechanism underlying the light response of the photo-receptor. The response elicited by an adapting stimulus had a large initial transient which declined to a smaller plateau. The peak current/photon decreased sharply during the declining phase of the transient and was relatively stable during the plateau. This indicates that the onset of light adaptation is delayed with respect to the onset of the response to the adapting stimulus. If the adaptational state just before the onset of each of a series of adapting stimuli was constant, the amplitude of the transient was a nearly linear function of intensity. When the total intensity was rapidly doubled (or halved) during a plateau response, the total current approximately doubled (or halved). We argue that the transition from transient to plateau, light-elicited changes of threshold, and the nonlinear function relating the plateau response to stimulus intensity all reflect changes of the responsiveness of the conductance-increase mechanism.