The spatial frequency sensitivity of bipolar cells

Retinal bipolar cells constitute the output stage of the outer layer of the retina. There are several constraints on the ability of the bipolar cell array to respond to the different spatial frequency components of the visual image, including (i) electrical coupling in the dendritic tree receiving receptor input; (iii) the "lateral inhibition" mediated by horizontal cells. Using simple mathematical models, we derive analytical expressions for the spatial frequency response of the bipolar cell array for the case in which horizontal cells are presynaptic to bipolar cells (feedforward model) and also for the case in which horizontal cells are presynaptic to receptors (feedback model). The results illustrate the importance of the three factors mentioned in determining the bipolar cells' properties. The optimal spatial frequency for stimulating the bipolar cell array, and the range of spatial frequencies transmitted onward to the inner plexiform layer, are thus related to the anatomical and electrical properties of the cells in the outer plexiform layer.     

Qualitative modeling of mechanoelectrical feedback in a ventricular cell

Mechanical changes in the heart muscle can influence its electrical properties through a process called mechanoelectrical feedback (MEF). This feedback can operate via changes in calcium dynamics during the cross-bridge cycle or via mechanosensitive (stretch-activated) channels. We present a four-variable ordinary differential equation (ODE) system that caricatures the electrical and mechanical activity of a ventricular cell and their mutual interactions. A three-variable excitable system with restitution properties of the FitzHugh-Nagumo type is coupled to a fourth equation which describes changes in cell length during a lightly loaded contraction. The resulting four-variable system models MEF in a cell and can be incorporated into spatially distributed models for mechanoelectric behavior during wave propagation in the cardiac tissue.     

Application of electrical analogs to metabolic control analysis: Linear pathways with multiple feedback

• 1.1. Using electrical analogs, we have presented a systematic procedure for calculating the flux control coefficients of linear metabolic pathways with multiple feedback loops.
• 2.2. In this method, an electrical analog circuit is constructed first for the unregulated pathway.
• 3.3. This circuit is subsequently modified in a step-by-step fashion to take into account the effect of each feedback loop in the pathway.
• 4.4. An analog circuit consists of resistances which are connected in series (or parallel) with a voltage (or current) source.
• 5.5. The flux control coefficients of the enzymes are represented by voltages across (or currents through) the resistances and are determined by an application of Ohm's law.
• 6.6. We have investigated the possible patterns in linear pathways with two feedback loops.
• 7.7. This is followed by an analysis of a linear pathway with an arbitrary pattern of feedback inhibition.

     

An electrical analogue model for frequency dependent lateral inhibition refering to the omega neurons in the auditory pathway of the cricket

An electrical analogue model for the recurrent lateral inhibition system formed by the omega neurons in the cricket's auditory pathway is described (Fig. 1A). The two reciprocally coupled inhibitory neurons are mimicked by the action of two inverting operational amplifiers in circuit with RLC combinations. The oscillatory properties of this reciprocal arrangement introduce a time delay in action of the feedback in the circuit, which corresponds to half the period of the characteristic frequency of the two-cell resonator. Varying degrees of coupling between the two inhibitory arms of the model produce a family of resonance curves (Fig. 4A) for frequency dependent contrast enhancement which allows the compromises observed in the physiological circuit to be discussed.In psychophysical experiments using the model circuit as an input stage for the human auditory pathway, frequency dependent lateral inhibition markedly improved identification of the apparent location of the sound source when the frequency of the input signals matched the resonant frequency of the circuit.Correspondence to this address     

Visual transduction: microvilli orchestrate photoreceptor responses to light

How do the microscopic properties of a photoreceptor shape the transformation of photon inputs into electrical outputs? Adaptive feedback, combined with stochastic sampling of light by transduction units, efficiently captures visual information.     

Electronic simulation of cones,horizontal cells and bipolar cells of generalized vertebrate cone retina

Electronic analogue of my theoretical model of generalized vertebrate cone retina [Siminoff: J. Theor. Biol. 86, 763 (1980)] is presented. Cone mosaic is simulated by 25x21 grid of phototransistors that have colored filters mounted in front of then to produce red-, green-, and blue-sensitive cones arranged in a trichromatic retina. Each retinal element is simulated by Summator-Integrator and unit gain voltage invertes are used to give correct polarities to output voltages. Dynamic properties of retinal elements are developed solely by temporal interplay of antagonistic input voltages with differing time courses, and spatial organization of receptive fields is developed by unit hexagons that precisely define cone input voltages to subsequent elements. Electronic model contains both color- and non-colorcoded channels. Negative feedback from L-horizontal cells to cones, electrical coupling of like-cones, and electrical coupling of like-horizontal cells are simulated by feedfoward circuits. Stray light is present due to light scattering properties of colored filters used to simulate color selectivety of cones. Stationary and moving spots of white and colored lights of varied sizes and intensities are used to study characteristics of electronic analogue. Results demonstrate practicality of electronic simulation to function analogous to real cone retinas to process visual stimuli and give information to higher centers as to size, shape, color and motion of objects in visual world.     

Electrical feedback in the chemical synapses

Electrical feedback in chemical synapses and the efficacy of synaptic transmission grow with the increase in the gap resistance, so they should be higher in invaginated synapses than in the flat ones. So the plastic changes in the invagination depth may provide a morphological basis for long-term changes in synaptic efficacy: long-term potentiation (LTP) in brain and retinal synapses. In retinal photoreceptor triad synapses, the electrical feedback can provide an "operational" (instantaneous) control of synaptic transmission.     

Co-operative dynamics in organelles

Some organelles produce elementary life phenomena which are characterized by the spontaneous formation and/or maintenance of ordered macroscopic dynamics like e.g. the shortening of sarcomeres in striated muscle and the transmission of electrical impulses in an axon. It has been widely accepted that such organelles are organized molecular systems where molecular elements work independently under constraint of a more or less rigid and regular structure of the system. On the other hand, such organelles should be regarded as self-organizing systems if the ordered macroscopic dynamics are self-organized. As the macroscopic dynamics gradually emerge, the microscopic dynamics of its elements become linked to each other through a feedback loop. It is crucial for the feedback loop to operate that the macroscopic dynamics are "free" in their behavior. In the present paper, it is pointed out that the traditional view of independent molecular elements has been obtained from experiments in which, by means of external constraint, the macroscopic dynamics is "clamped". Under such conditions, the self-organizing system may behave as an organized one. Based on synergetics we propose criterions for proving self-organizing systems, and, by applying the criterions, we conclude that skeletal muscle actomysin is a co-operative element in the sense of self-organization.     

Three-dimensional analysis of regional cardiac function: a model of rabbit ventricular anatomy

The three-dimensional geometry and anisotropic properties of the heart give rise to nonhomogeneous distributions of stress, strain, electrical activation and repolarization. In this article we review the ventricular geometry and myofiber architecture of the heart, and the experimental and modeling studies of three-dimensional cardiac mechanics and electrophysiology. The development of a three-dimensional finite element model of the rabbit ventricular geometry and fiber architecture is described in detail. Finally, we review the experimental results, from the level of the cell to the intact organ, which motivate the development of coupled three-dimensional models of cardiac electromechanics and mechanoelectric feedback.     

Drugs that interact with cardiac electro-mechanics: old and new targets for treatment

The concept of mechano-electrical feedback was derived from the observation that a short stretch applied to the beating heart can invoke an electrical response in the form of an afterdepolarization or a premature ventricular beat. More recent work has identified stretch-activated channels whose specific inhibition might help to treat atrial fibrillation in the near future. But the interaction between electrical and mechanical function of the heart is a continuum from short-term (within milliseconds) to long-term (within weeks or months) effects. The long-term effects of pressure overload have been well-described on the molecular and cellular level, and substances that interact with these processes are used in clinical routine in the care of patients with cardiac hypertrophy and heart failure. These treatments help to prevent lethal arrhythmias (sudden death) and potentially atrial fibrillation. The intermediate interaction between mechanical and electrical function of the heart is less well-understood. Several recently identified regulatory mechanisms may provide novel antiarrhythmic targets associated with the "intermediate" response of the myocardium to stretch.     

A theory of synchronization of heart pace-maker cells

This paper presents a theory of synchronization of heart pace-maker cells. The interaction between cells is supposed to be electrical. The most important result is that when the leakage current is small and the junction resistance low, the synchronizing mechanism may become the electrical coupling. When the membrane electrical properties are described by the BVP model, the result is proved analytically. When Noble (1962) equations are used the result is demonstrated by simulation with the computer.     

Pattern generation in the lobster (Panulirus) stomatogastric ganglion

There are a number of perspectives gained from a quantitative analysis of the pyloric system which may be applicable to other simple pattern generators: 1. The system is organized around a dominant, endogenously-bursting neuron group, and its properties are tailored to that dominance. In particular, synaptic strengths and firing frequencies of that group appear just sufficient to suppress postsynaptic "follower" cells if the latter are not too highly excited. 2. Repetitive firing properties of follower neurons are such as to facilitate their switch-like mode of activity. This includes pacemaker response nonlinearities, rebound properties, and "burstiness" properties. 3. Proper sequencing of follower cells may be controlled by particular synaptic strengths and time-courses, feedback on the oscillator cells, and functional cellular properties of follower neurons (e.g., rebound; see also next paper). All such properties interact and must be tuned to each other for proper patterns to result.     

A biopolymer transistor: electrical amplification by microtubules

Microtubules (MTs) are important cytoskeletal structures engaged in a number of specific cellular activities, including vesicular traffic, cell cyto-architecture and motility, cell division, and information processing within neuronal processes. MTs have also been implicated in higher neuronal functions, including memory and the emergence of "consciousness". How MTs handle and process electrical information, however, is heretofore unknown. Here we show new electrodynamic properties of MTs. Isolated, taxol-stabilized MTs behave as biomolecular transistors capable of amplifying electrical information. Electrical amplification by MTs can lead to the enhancement of dynamic information, and processivity in neurons can be conceptualized as an "ionic-based" transistor, which may affect, among other known functions, neuronal computational capabilities.     

Electromechanical model of excitable tissue to study reentrant cardiac arrhythmias

We introduce the concept of a contracting excitable medium that is capable of conducting non-linear waves of excitation that in turn initiate contraction. Furthermore, these kinematic deformations have a feedback effect on the excitation properties of the medium. Electrical characteristics resemble basic models of cardiac excitation that have been used to successfully study mechanisms of reentrant cardiac arrhythmias in electrophysiology. We present a computational framework that employs electromechanical and mechanoelectric feedback to couple a three-variable FitzHugh–Nagumo-type excitation-tension model to the non-linear stress equilibrium equations, which govern large deformation hyperelasticity. Numerically, the coupled electromechanical model combines a finite difference method approach to integrate the excitation equations, with a Galerkin finite element method to solve the equations governing tissue mechanics. We present example computations demonstrating various effects of contraction on stationary rotating spiral waves and spiral wave break. We show that tissue mechanics significantly contributes to the dynamics of electrical propagation, and that a coupled electromechanical approach should be pursued in future electrophysiological modelling studies.     

Systemanalytische Untersuchung eines aufgeschnittenen Regelkreises,der die Beinstellung der Stabheuschrecke Carausius morosus kontrolliert: Kraftmessungen an den Antagonisten Flexor und Extensor tibiae

In the leg of the stick insect Carausius morosus there exists a feedback loop which controls the position of the femur-tibia joint (Bässler, 1965). This feedback mechanism is broken to investigate the open loop system. As output the forces of the two antagonistic muscles flexor tibiae and extensor tibiae are measured separately. As input the feedback transducer of the control mechanism, a chordotonal organ, is stimulated by different kinds of input functions: sine-, step-, delta-, rectangular-and ramp functions. As a qualitative result one can say, that both the flexor-system and the extensor-system have rectifying and high-pass filter properties. However, the comparison between responses to different input functions show that the quantitative properties of this high-pass filter change very strongly with the shape of the input function. Therefore the existence of different nonlinearities has to be assumed.

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Mit Unterstützung der Deutschen Forschungsgemeinschaft (Nr. Ba 578/1)

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Die Arbeit enthält einen Teil der Dissertation von J. Storrer     

Electrophysiological properties of the membrane of smooth muscle cells from bovine lymphatic vessels

Using single sucrose gap technique, studies have been made on electrophysiological properties of the membrane in myocytes of the lymphatic vessels in the ox Bos taurus. It was shown that electrical stimulation does not induce tetanic contraction in the myocytes. The results obtained indicate strong similarity between electrophysiological properties of the myocytes in the lymphatic vessels and those of the myocardial cells in homoiotherms. Refractory state which follows the action potential, accounts for a possibility of rhythmic activity in the myocytes of the lymphatic vessels. Both single and rhythmic stimulation produce in the myocytes the "all-or-none" response. The main factor determining the level of excitability in the myocytes is the intravascular pressure. The latter exerts its influence on contractile activity via changes in the electrical activity (the membrane potential, duration of the plateau phase and the number of fast peak potentials on this plateau).     

Acetohydroxyacid synthase isozyme I from Escherichia coli has unique catalytic and regulatory properties

AHAS I is an isozyme of acetohydroxyacid synthase which is apparently unique to enterobacteria. It has been known for over 20 years that it has many properties which are quite different from those of the other two enterobacterial AHASs isozymes, as well as from those of "typical" AHASs which are single enzymes in a given organism. These include a unique mechanism for regulation of expression and the absence of a preference for forming acetohydroxybutyrate. We have cloned the two subunits, ilvB and ilvN, of this Escherichia coli isoenzyme and examined the enzymatic properties of the purified holoenzyme and the enzyme reconstituted from purified subunits. Unlike other AHASs, AHAS I demonstrates cooperative feedback inhibition by valine, and the kinetics fit closely to an exclusive binding model. The formation of acetolactate by AHAS I is readily reversible and acetolactate can act as substrate for alternative AHAS I-catalyzed reactions.     

Hemopoietic regulatory factors in human hemopoietic failures

There are two distinct hemopoietic activities in human serum that do not have the properties of the known hemopoietic lymphokines. These two activities appear not to be produced by immune competent cells. "Direct" stimulatory activity acts in primary target cultures of normal marrow. There does not appear to be a feedback mechanism between bone marrow failure and "direct" activity; it appears to reflect ongoing disease. Indirect "releaser" activity stimulates peripheral blood cells to produce hemopoietic growth factors. It is invariably elevated when release of hemopoietic growth factors is poor, indicating that a feedback mechanism exists. The peripheral blood cells of young patients, particularly young girls, respond poorly to autologous "releaser" stimulation. Results of treatment with ALG in this group are poor. However, all patients with aplastic anemia appear capable of producing adequate amounts "releaser" factor.     

DNA hybridization sensor based on pentacene thin film transistor

A DNA hybridization sensor using pentacene thin film transistors (TFTs) is an excellent candidate for disposable sensor applications due to their low-cost fabrication process and fast detection. We fabricated pentacene TFTs on glass substrate for the sensing of DNA hybridization. The ss-DNA (polyA/polyT) or ds-DNA (polyA/polyT hybrid) were immobilized directly on the surface of the pentacene, producing a dramatic change in the electrical properties of the devices. The electrical characteristics of devices were studied as a function of DNA immobilization, single-stranded vs. double-stranded DNA, DNA length and concentration. The TFT device was further tested for detection of λ-phage genomic DNA using probe hybridization. Based on these results, we propose that a "label-free" detection technique for DNA hybridization is possible through direct measurement of electrical properties of DNA-immobilized pentacene TFTs.