On the nerve impulse equation: The dynamic responses of nerve impulse

With the assumption of dipole interaction with the membrane matrix, the dipole barrier under an applied field shows a minimum in its time transient. Kinetic equations governing the migration of ions are presented. Na⁺ activation, Na⁺ inactivation and K⁺ delay are all part of the same mechanism in this model with no other separate assumptions needed. Voltage Clamp equation and action potential equation are presented. Supported in part by Physics Research Center, National Science Council, The Republic of China.     

Effects of kinetic coupling on experimentally determined electron transfer parameters

Coupled electron transfer (ET) occurs when a relatively slow nonadiabatic ET reaction is preceded by a rapid but unfavorable adiabatic reaction that is required to activate the system for ET. As a consequence of this, the observed ET rate constant (k(ET)) is an apparent value equal to the product of the true k(ET) and the equilibrium constant for the preceding reaction step. Analysis of such reactions by ET theory may yield erroneous values for the reorganizational energy (lambda), electronic coupling (H(AB)), and ET distance that are associated with the true k(ET). If the DeltaG degrees dependence of the rate of a coupled ET reaction is analyzed, an accurate value of lambda will be obtained but the experimentally determined H(AB) will be less than the true H(AB) and the ET distance will be greater than the true distance. If the temperature dependence of the rate of a coupled ET reaction is analyzed, the experimentally determined value of lambda will be greater than the true lambda. The magnitude of this apparent lambda will depend on the magnitude of DeltaH degrees for the unfavorable reaction step that precedes ET. The experimentally determined values of H(AB) and distance will be accurate if DeltaS degrees for the preceding reaction is zero. If DeltaS degrees is positive, then H(AB) will be greater than the true value and the distance will be less than the true value. If DeltaS degrees is negative, then H(AB) will be less than the true value and the distance will be greater than the true value. Data sets for coupled ET reactions have been simulated and analyzed by ET theory to illustrate these points.     

Effect doublet impulse sequences on the transient and steady responses in the computer-simulated nerve cell

The effects of doublet impulse sequences of the excitatory axon on the output response as firing probability (pr.) in the computer-simulated nerve cell were examined. A simple model was formulated to simulate the nerve cell, including the property that the resetting potential is influenced by the final membrane potential in the previous stage before firing. The relationship between input sequences with alternating long and short interval at the same mean rate and the transient and steady responses of the nerve cell was investigated. In this simulation, three summarized results were obtained: i) The responses were very sensitive to changing small size of excitatory post-synaptic potential (EPSP), especially in the firing stage of the transient state. ii) In the transient state, the size of characteristic area of responses was depending upon the size of absolute refractory period (ARP). The rise for shorter intervals was faster than that for longer intervals, agreeing well with part of the experimental results from the crayfish claw opener muscles. The transient responses were almost finished before the fifth firing. iii) In the steady state, the doublet impulse sequences usually produced the minimum response or valley-like response at which the doublet interval T _dwas 20 and/or 25 ms. These effects related to the characteristic areas in the transient responses.     

Comparison of experimentally determined protein structures by solution of Bloch equations

Nuclear Overhauser enhancement (NOESY) spectra were theoretically generated by solving the generalized Bloch equations with the appropriate initial conditions. The input to the equations were the coordinates of the protons of two similar crystal structures of basic pancreatic trypsin inhibitor. The two NOESY spectra obtained were compared to published experimental spectra of the protein in solution. It was found that the two crystal structures of basic pancreatic trypsin inhibitor give different theoretical spectra. The solution of the Bloch equations is very sensitive to small variations in the distance between protons (approx. 0.2 A), and to differences in the surrounding configurations. The method allows a detailed comparison of the crystal and solution structures of proteins. The structure of the trypsin inhibitor in solution was found to be similar to either one or the other crystal forms in different regions of the molecule.     

Functional differentiation of fore- and hindlimb muscles inMacaca fuscata determined on the basis of enzymatic activities

When the functional differentiation of 83 kinds of limb and trunk muscles ofMacaca fuscata was investigated on the basis of the activities of two glycolytic enzymes [lactate dehydrogenase (LDH) and aldolase] and one oxidative enzyme [succinate dehydrogenase (SDH)], the forelimb rather than the hindlimb muscles proved have higher oxidative activities. These results indicated that, inMacaca fuscata, the forelimb muscles have a higher resistance to fatigue, and that the hindlimb muscles have a higher tetanic tension on the basis of the relationships between enzymatic activities and functional properties of the muscle fiber types. These findings were interpreted in relation to the fact thatMacaca fuscata is a quadrupedal primate with arboreal habits, as compared with nonprimate terrestrial quadrupeds. The two-joint muscles and the superficial muscles contract more rapidly than do the other muscles in the hindlimb, thereby suggesting that both types of muscles readily adapt to quick movement.     

The physical basis of nerve impulse conduction the irreversible thermodynamic analysis of the active state

This communication reports the thermodynamic analysis of the active state in nonmyelinated axons; it is the first step in the development of a theory of the physical basis of nerve impulse transport. The thermodynamic analysis enables one to make proper identification of material and thermal diffusion coefficients and conductivities associated with the impulse transport. Future additions to the details of the theory will involve consideration of molecular models of the axon active state. The complete macroscopic thermodynamic and microscopic statistical mechanical analyses will provide the links between the model representations and the measured quantities, e.g. conductivities and action potentials.This paper is divided into two parts. Part I is an introduction to the representation of the nerve axon used here and a general discussion of the results of the analysis of the active state obtained rigorously in Part II. The analysis contained in Part II involves an examination of the phenomenological transport equations for the coupled material (ionic) and thermal diffusion problems. By means of suitable transformations of the transport equations a correspondence with the theory of thermal explosions results. This correspondence therefore allows a detailed examination of the processes of impulse initiation and propagation.The thermodynamic analysis is macroscopic and necessarily phenomenological. Nevertheless, in spite of the macroscopic viewpoint it does enable one to make some predictions of a microscopic nature. In particular, these predictions concern the mechanism of synaptic conduction, the nature of impulse initiation at sensory receptors, and very importantly, the nature of allowable microscopic models of the impulse transport in the axon membrane. These points are discussed in the text of the paper.     

Corticofugal feedback can reduce the visual latency of responses to antagonistic stimuli

 A biophysically realistical model of the primary visual pathway is designed, including feedback connections from the visual cortex to the lateral geniculate nucleus (LGN) – the so-called corticofugal pathway. The model comprises up to 10 000 retina and LGN cells divided into the ON and the OFF pathway according to their contrast response characteristics. An additional 6000 cortical simple cells are modeled. Apart from the direct excitatory afferent pathway we include strong mutual inhibition between the ON and the OFF subsystems. In addition, we propose a novel type of paradoxical corticofugal connection pattern which links ON dominated cortical simple cells to OFF-center LGN cells and vice versa. In accordance with physiological findings these connections are weakly excitatory and do not interfere with the steady-state responses to constant illumination, because during the steady-state inhibition arising from the active pathway effectively silences the nonstimulated pathway. At the moment of a contrast reversal the effect of the paradoxical connection pattern comes into play and the depolarization of the previously silent channel is accelerated, leading to a latency reduction of up to 4 ms using moderate synaptic weights. With increased weights reductions of more than 10 ms can be achieved. We introduce different synaptic characteristics for the feedback (AMPA, NMDA, AMPA+NMDA) and show that the strongest latency reduction is obtained for a combination of the membrane channels (i.e., AMPA+NMDA). The effect of the proposed paradoxical connection pattern is self-regulating; because the levels of inhibition and paradoxical excitation are always driven by the same inputs (strong inhibition is counterbalanced by a stronger paradoxical excitation and vice versa). In addition, the latency reduction for a contrast inversion which ends at a small absolute contrast level (small contrast step) is stronger than the reduction for an inversion with large final contrast (large contrast step). This leads to a more pronounced reduction in the reaction times for weak stimuli. Thus, reaction time differences for different contrast steps are smoothed out. Received: 22 January 1996/Accepted in revised form: 20 May 1996     

Relative latency of responses of chemoreceptor afferents from aortic and carotid bodies

Discharges from aortic and carotid body chemoreceptor afferents were simultaneously recorded in 18 anesthetized cats to test the hypothesis that aortic chemoreceptors, because of their proximity to the heart, respond to changes in arterial blood gases before carotid chemoreceptors. We found that carotid chemoreceptor responses to the onset of hypoxia and hypercapnia, and to the intravenously administered excitatory drugs (cyanide, nicotine, and doxapram), preceded those of aortic chemoreceptors. Postulating that this unexpected result was due to differences in microcirculation and mass transport, we also investigated their relative speed of responses to changes in arterial blood pressure. The aortic chemoreceptors responded to decreases in arterial blood pressure before the carotid chemoreceptors, supporting the idea that the aortic body has microcirculatory impediments not generally present in the carotid body. These findings strengthened the concept that carotid bodies are more suited for monitoring blood gas changes due to respiration, whereas aortic bodies are for monitoring circulation.     

Gravitropic responses of the Avena coleoptile in space and on clinostats. I. Gravitropic response thresholds

We conducted a series of gravitropic experiments on Avena coleoptiles in the weightlessness environment of Spacelab. The purpose was to test the threshold stimulus, reciprocity rule and autotropic reactions to a range of g-force stimulations of different intensities and durations The tests avoided the potentially complicating effects of earth's gravity and the interference from clinostat ambiguities. Using slow-speed centrifuges, coleoptiles received transversal accelerations in the hypogravity range between 0.1 and 1.0 g over periods that ranged from 2 to 130 min. All responses that occurred in weightlessness were compared to clinostal experiments on earth using the same apparatus.
Characteristic gravitropistic response patterns of Avena were not substantially different from those observed in ground-based experiments. Gravitropic presentation times were extrapolated. The threshold at 1.0 g was less than 1 min (shortest stimulation time 2 min), in agreement with values obtained on the ground. The least stimulus tested, 0.1 g for 130 min, produced a significant response. Therefore the absolute threshold for a gravitropic response is less than 0.1 g.     

Redox-sensing is the basis of photophobic responses in cyanobacteria

Abstract Cyanobacteria lack specialized photoreceptors for photophobic responses (PPR), the action spectrum for photosynthesis coinciding with that for PPR. In the presence of 3-(3',4'-dichlorophenyl)-1,1-dimethyl urea) (DCMU), which blocks electron transfer prior to plastoquinone (PQ), turning on the light increased the membrane potential, but simultaneously evoked an unusual phobic response, presumably due to oxidation of PQ · H₂ via photosystem I (PS I). White light and the PQ reductant, (DQ · H₂), acted as attractants and produced methylation of a 40 kDa membrane peptide. Repellents, an uncoupler, carbonyl cyanide m -chlorophenylhydrazone (CCCP), and an oxidant, tetramethyl- p -hydroquinone(duroquinon) (DQ), caused demethylation. The results are interpreted in the framework of Häder's 'electron pool hypothesis', according to which PQ · H₂ level governs PPR. It is further concluded that the same system is the mechanism of pmf-sensing:      

Regulatory T cell adjustment of quorum growth thresholds and the control of local immune responses

The consequences of regulatory T cell (Treg) inhibition of interleukine 2 secretion is examined by mathematical modelling. We demonstrate that cytokine dependent growth exhibits a quorum T cell population threshold that determines if immune responses develop on activation. Secretion inhibition manipulates the growth dynamics and effectively increases the quorum threshold, i.e. to develop immune responses a higher number of T cells need to be activated. Thus Treg induced secretion inhibition can provide a mechanism for tissue specific regulation of the balance between suppression (control) and immune responses, a balance that can be varied at the local tissue level through the regulation of the local active Treg population size. However, nonspecific inhibition is prone to escape of initially controlled autoimmune T cells through cross reactivity to pathogens and bystander proliferation on unrelated immune responses.     

Phenotypic responses of wild barley to experimentally imposed water stress

Responses to water stress within a population of wild barley from Tabigha, Israel, were examined. The population's distribution spans two soil types: Terra Rossa (TR) and Basalt (B). Seeds were collected from plants along a 100 m transect; 24 genotypes were sampled from TR and 28 from B. Due to different soil water-holding capacities, plants growing on TR naturally experience more intense drought than plants growing on B. In a glasshouse experiment, water was withheld from plants for two periods (10 d and 14 d) after flag leaf emergence. A total of 15 agronomic, morphological, developmental, and fertility related traits were examined by analysis of variance (ANOVA). Ten of these traits were significantly affected by the treatment. A high degree of phenotypic variation was found in the population with significant genotypextreatment and soil typextreatment interactions. Principal component analysis (PCA) was performed using combined control and stress treatment data sets. The first three principal components (pc) explained 88.8% of the variation existing in the population with pc1 (47.9%) comprising yield-related and morphological traits, pc2 (22.9%) developmental characteristics and pc3 (18.0%) fertility-related traits. The relative performance of individual genotypes was determined and water stress tolerant genotypes identified. TR genotypes were significantly less affected by the imposed water stress than B genotypes. Moreover, TR genotypes showed accelerated development under water deficit conditions. Data indicate that specific genotypes demonstrating differential responses may be useful for comparative physiological studies, and that TR genotypes exhibiting yield stability may have value for breeding barley better adapted to drought.     

Pathological and haematological responses of cats experimentally infected with Toxocara canis larvae

Responses of eight adult cats to one or two infections with larvae of Toxocara canis were studied up to 39 days post infection (DPI). Clinically, all cats remained normal throughout the study. The major necropsy finding was multifocal, white to grey nodules mainly within the liver, lungs and kidneys; live larvae were found in liver nodules. Histologically, the nodules were eosinophilic granulomas. Granulomas containing a larval section were observed mainly within the liver. All infected cats had variably severe, eosinophilic arteritis and bronchiolitis and medial hypertrophy and hyperplasia of the pulmonary arteries. No inflammatory eye lesions were detected. Circulating eosinophil levels increased in all infected cats; peak values of 15,790 and 10,050 eosinophils microliters-1 were observed at 25 or 32 DPI in cats receiving a single or double infection, respectively. Bone marrow of all infected cats exhibited marked eosinophilic hyperplasia which did not correlate with the level of circulating eosinophilia. Thus, infection of cats by the larvae of T. canis causes disseminated eosinophilic and granulomatous disease with marked pulmonary artery and airway lesions.     

Comparison of simulated and experimentally determined dynamics for a variant of the Lacl DNA-binding domain, Nlac-P.

Recent advances in the experimentally determined structures and dynamics of the domains within LacI provide a rare context for evaluating dynamics calculations. A 1500-ps trajectory was simulated for a variant of the LacI DNA-binding domain, which consists of the first three helices in LacI and the hinge helix of the homologous PurR. Order parameters derived from dynamics simulations are compared to those obtained for the LacI DNA-binding domain with 15N relaxation NMR spectroscopy (Slijper et al., 1997. Biochemistry. 36:249-254). The MD simulations suggest that the unstructured loop between helices II and III does not exist in a discrete state under the conditions of no salt and neutral pH, but occupies a continuum of states between the DNA-bound and free structures. Simulations also indicate that the unstructured region between helix III and the hinge helix is very mobile, rendering motions of the hinge helix essentially independent of the rest of the protein. Finally, the alpha-helical hydrogen bonds in the hinge helix are broken after 1250 ps, perhaps as a prelude to helix unfolding.     

A method of evoking fast baroreceptor responses for the measurement of the baroreflex latency.

A method for measurement of latency in the baroreflex is described. Standardised square pressure pulse was applied to the isolated carotid sinus and simultaneous recordings of the carotid sinus nerve or sympathetic fibers were performed. Relatively short time of the increase of the pressure makes possible more exact measurements of latency in the baroreflex than other known methods used for this purpose.