Sample records for action potential configuration

  1. Role of action potential configuration and the contribution of Ca2+ and K+ currents to isoprenaline-induced changes in canine ventricular cells

    PubMed Central

    Szentandrássy, N; Farkas, V; Bárándi, L; Hegyi, B; Ruzsnavszky, F; Horváth, B; Bányász, T; Magyar, J; Márton, I; Nánási, PP

    2012-01-01

    BACKGROUND AND PURPOSE Although isoprenaline (ISO) is known to activate several ion currents in mammalian myocardium, little is known about the role of action potential morphology in the ISO-induced changes in ion currents. Therefore, the effects of ISO on action potential configuration, L-type Ca2+ current (ICa), slow delayed rectifier K+ current (IKs) and fast delayed rectifier K+ current (IKr) were studied and compared in a frequency-dependent manner using canine isolated ventricular myocytes from various transmural locations. EXPERIMENTAL APPROACH Action potentials were recorded with conventional sharp microelectrodes; ion currents were measured using conventional and action potential voltage clamp techniques. KEY RESULTS In myocytes displaying a spike-and-dome action potential configuration (epicardial and midmyocardial cells), ISO caused reversible shortening of action potentials accompanied by elevation of the plateau. ISO-induced action potential shortening was absent in endocardial cells and in myocytes pretreated with 4-aminopyridine. Application of the IKr blocker E-4031 failed to modify the ISO effect, while action potentials were lengthened by ISO in the presence of the IKs blocker HMR-1556. Both action potential shortening and elevation of the plateau were prevented by pretreatment with the ICa blocker nisoldipine. Action potential voltage clamp experiments revealed a prominent slowly inactivating ICa followed by a rise in IKs, both currents increased with increasing the cycle length. CONCLUSIONS AND IMPLICATIONS The effect of ISO in canine ventricular cells depends critically on action potential configuration, and the ISO-induced activation of IKs– but not IKr– may be responsible for the observed shortening of action potentials. PMID:22563726

  2. Role of action potential configuration and the contribution of C²⁺a and K⁺ currents to isoprenaline-induced changes in canine ventricular cells.

    PubMed

    Szentandrássy, N; Farkas, V; Bárándi, L; Hegyi, B; Ruzsnavszky, F; Horváth, B; Bányász, T; Magyar, J; Márton, I; Nánási, P P

    2012-10-01

    Although isoprenaline (ISO) is known to activate several ion currents in mammalian myocardium, little is known about the role of action potential morphology in the ISO-induced changes in ion currents. Therefore, the effects of ISO on action potential configuration, L-type Ca²⁺ current (I(Ca)), slow delayed rectifier K⁺ current (I(Ks)) and fast delayed rectifier K⁺ current (I(Kr)) were studied and compared in a frequency-dependent manner using canine isolated ventricular myocytes from various transmural locations. Action potentials were recorded with conventional sharp microelectrodes; ion currents were measured using conventional and action potential voltage clamp techniques. In myocytes displaying a spike-and-dome action potential configuration (epicardial and midmyocardial cells), ISO caused reversible shortening of action potentials accompanied by elevation of the plateau. ISO-induced action potential shortening was absent in endocardial cells and in myocytes pretreated with 4-aminopyridine. Application of the I(Kr) blocker E-4031 failed to modify the ISO effect, while action potentials were lengthened by ISO in the presence of the I(Ks) blocker HMR-1556. Both action potential shortening and elevation of the plateau were prevented by pretreatment with the I(Ca) blocker nisoldipine. Action potential voltage clamp experiments revealed a prominent slowly inactivating I(Ca) followed by a rise in I(Ks) , both currents increased with increasing the cycle length. The effect of ISO in canine ventricular cells depends critically on action potential configuration, and the ISO-induced activation of I(Ks) - but not I(Kr) - may be responsible for the observed shortening of action potentials. © 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.

  3. Effects of tacrolimus on action potential configuration and transmembrane ion currents in canine ventricular cells.

    PubMed

    Szabó, László; Szentandrássy, Norbert; Kistamás, Kornél; Hegyi, Bence; Ruzsnavszky, Ferenc; Váczi, Krisztina; Horváth, Balázs; Magyar, János; Bányász, Tamás; Pál, Balázs; Nánási, Péter P

    2013-03-01

    Tacrolimus is a commonly used immunosuppressive agent which causes cardiovascular complications, e.g., hypertension and hypertrophic cardiomyopathy. In spite of it, there is little information on the cellular cardiac effects of the immunosuppressive agent tacrolimus in larger mammals. In the present study, therefore, the concentration-dependent effects of tacrolimus on action potential morphology and the underlying ion currents were studied in canine ventricular cardiomyocytes. Standard microelectrode, conventional whole cell patch clamp, and action potential voltage clamp techniques were applied in myocytes enzymatically dispersed from canine ventricular myocardium. Tacrolimus (3-30 μM) caused a concentration-dependent reduction of maximum velocity of depolarization and repolarization, action potential amplitude, phase-1 repolarization, action potential duration, and plateau potential, while no significant change in the resting membrane potential was observed. Conventional voltage clamp experiments revealed that tacrolimus concentrations ≥3 μM blocked a variety of ion currents, including I(Ca), I(to), I(K1), I(Kr), and I(Ks). Similar results were obtained under action potential voltage clamp conditions. These effects of tacrolimus developed rapidly and were fully reversible upon washout. The blockade of inward currents with the concomitant shortening of action potential duration in canine myocytes is the opposite of those observed previously with tacrolimus in small rodents. It is concluded that although tacrolimus blocks several ion channels at higher concentrations, there is no risk of direct interaction with cardiac ion channels when applying tacrolimus in therapeutic concentrations.

  4. Effects of Action Relations on the Configural Coding between Objects

    ERIC Educational Resources Information Center

    Riddoch, M. J.; Pippard, B.; Booth, L.; Rickell, J.; Summers, J.; Brownson, A.; Humphreys, G. W.

    2011-01-01

    Configural coding is known to take place between the parts of individual objects but has never been shown between separate objects. We provide novel evidence here for configural coding between separate objects through a study of the effects of action relations between objects on extinction. Patients showing visual extinction were presented with…

  5. A physical action potential generator: design, implementation and evaluation.

    PubMed

    Latorre, Malcolm A; Chan, Adrian D C; Wårdell, Karin

    2015-01-01

    The objective was to develop a physical action potential generator (Paxon) with the ability to generate a stable, repeatable, programmable, and physiological-like action potential. The Paxon has an equivalent of 40 nodes of Ranvier that were mimicked using resin embedded gold wires (Ø = 20 μm). These nodes were software controlled and the action potentials were initiated by a start trigger. Clinically used Ag-AgCl electrodes were coupled to the Paxon for functional testing. The Paxon's action potential parameters were tunable using a second order mathematical equation to generate physiologically relevant output, which was accomplished by varying the number of nodes involved (1-40 in incremental steps of 1) and the node drive potential (0-2.8 V in 0.7 mV steps), while keeping a fixed inter-nodal timing and test electrode configuration. A system noise floor of 0.07 ± 0.01 μV was calculated over 50 runs. A differential test electrode recorded a peak positive amplitude of 1.5 ± 0.05 mV (gain of 40x) at time 196.4 ± 0.06 ms, including a post trigger delay. The Paxon's programmable action potential like signal has the possibility to be used as a validation test platform for medical surface electrodes and their attached systems.

  6. A rabbit ventricular action potential model replicating cardiac dynamics at rapid heart rates.

    PubMed

    Mahajan, Aman; Shiferaw, Yohannes; Sato, Daisuke; Baher, Ali; Olcese, Riccardo; Xie, Lai-Hua; Yang, Ming-Jim; Chen, Peng-Sheng; Restrepo, Juan G; Karma, Alain; Garfinkel, Alan; Qu, Zhilin; Weiss, James N

    2008-01-15

    Mathematical modeling of the cardiac action potential has proven to be a powerful tool for illuminating various aspects of cardiac function, including cardiac arrhythmias. However, no currently available detailed action potential model accurately reproduces the dynamics of the cardiac action potential and intracellular calcium (Ca(i)) cycling at rapid heart rates relevant to ventricular tachycardia and fibrillation. The aim of this study was to develop such a model. Using an existing rabbit ventricular action potential model, we modified the L-type calcium (Ca) current (I(Ca,L)) and Ca(i) cycling formulations based on new experimental patch-clamp data obtained in isolated rabbit ventricular myocytes, using the perforated patch configuration at 35-37 degrees C. Incorporating a minimal seven-state Markovian model of I(Ca,L) that reproduced Ca- and voltage-dependent kinetics in combination with our previously published dynamic Ca(i) cycling model, the new model replicates experimentally observed action potential duration and Ca(i) transient alternans at rapid heart rates, and accurately reproduces experimental action potential duration restitution curves obtained by either dynamic or S1S2 pacing.

  7. Reconstruction of the action potential of ventricular myocardial fibres

    PubMed Central

    Beeler, G. W.; Reuter, H.

    1977-01-01

    1. A mathematical model of membrane action potentials of mammalian ventricular myocardial fibres is described. The reconstruction model is based as closely as possible on ionic currents which have been measured by the voltage-clamp method. 2. Four individual components of ionic current were formulated mathematically in terms of Hodgkin—Huxley type equations. The model incorporates two voltage- and time-dependent inward currents, the excitatory inward sodium current, iNa, and a secondary or slow inward current, is, primarily carried by calcium ions. A time-independent outward potassium current, iK1, exhibiting inward-going rectification, and a voltage- and time-dependent outward current, ix1, primarily carried by potassium ions, are further elements of the model. 3. The iNa is primarily responsible for the rapid upstroke of the action potential, while the other current components determine the configuration of the plateau of the action potential and the re-polarization phase. The relative importance of inactivation of is and of activation of ix1 for termination of the plateau is evaluated by the model. 4. Experimental phenomena like slow recovery of the sodium system from inactivation, frequency dependence of the action potential duration, all-or-nothing re-polarization, membrane oscillations are adequately described by the model. 5. Possible inadequacies and shortcomings of the model are discussed. PMID:874889

  8. Cardiac action potential imaging

    NASA Astrophysics Data System (ADS)

    Tian, Qinghai; Lipp, Peter; Kaestner, Lars

    2013-06-01

    Action potentials in cardiac myocytes have durations in the order of magnitude of 100 milliseconds. In biomedical investigations the documentation of the occurrence of action potentials is often not sufficient, but a recording of the shape of an action potential allows a functional estimation of several molecular players. Therefore a temporal resolution of around 500 images per second is compulsory. In the past such measurements have been performed with photometric approaches limiting the measurement to one cell at a time. In contrast, imaging allows reading out several cells at a time with additional spatial information. Recent developments in camera technologies allow the acquisition with the required speed and sensitivity. We performed action potential imaging on isolated adult cardiomyocytes of guinea pigs utilizing the fluorescent membrane potential sensor di-8-ANEPPS and latest electron-multiplication CCD as well as scientific CMOS cameras of several manufacturers. Furthermore, we characterized the signal to noise ratio of action potential signals of varying sets of cameras, dye concentrations and objective lenses. We ensured that di-8-ANEPPS itself did not alter action potentials by avoiding concentrations above 5 μM. Based on these results we can conclude that imaging is a reliable method to read out action potentials. Compared to conventional current-clamp experiments, this optical approach allows a much higher throughput and due to its contact free concept leaving the cell to a much higher degree undisturbed. Action potential imaging based on isolated adult cardiomyocytes can be utilized in pharmacological cardiac safety screens bearing numerous advantages over approaches based on heterologous expression of hERG channels in cell lines.

  9. Action potentials in retinal ganglion cells are initiated at the site of maximal curvature of the extracellular potential.

    PubMed

    Eickenscheidt, Max; Zeck, Günther

    2014-06-01

    The initiation of an action potential by extracellular stimulation occurs after local depolarization of the neuronal membrane above threshold. Although the technique shows remarkable clinical success, the site of action and the relevant stimulation parameters are not completely understood. Here we identify the site of action potential initiation in rabbit retinal ganglion cells (RGCs) interfaced to an array of extracellular capacitive stimulation electrodes. We determine which feature of the extracellular potential governs action potential initiation by simultaneous stimulation and recording RGCs interfaced in epiretinal configuration. Stimulation electrodes were combined to areas of different size and were presented at different positions with respect to the RGC. Based on stimulation by electrodes beneath the RGC soma and simultaneous sub-millisecond latency measurement we infer axonal initiation at the site of maximal curvature of the extracellular potential. Stimulation by electrodes at different positions along the axon reveals a nearly constant threshold current density except for a narrow region close to the cell soma. These findings are explained by the concept of the activating function modified to consider a region of lower excitability close to the cell soma. We present a framework how to estimate the site of action potential initiation and the stimulus required to cross threshold in neurons tightly interfaced to capacitive stimulation electrodes. Our results underscore the necessity of rigorous electrical characterization of the stimulation electrodes and of the interfaced neural tissue.

  10. Air Launch: Examining Performance Potential of Various Configurations and Growth Options

    NASA Technical Reports Server (NTRS)

    Waters, Eric D.; Creech, Dennis M.; Philips, Alan

    2013-01-01

    The Advanced Concepts Office at NASA's George C. Marshall Space Flight Center conducted a high-level analysis of various air launch vehicle configurations, objectively determining maximum launch vehicle payload while considering carrier aircraft capabilities and given dimensional constraints. With the renewed interest in aerial launch of low-earth orbit payloads, referenced by programs such as Stratolaunch and Spaceship2, there existed a need to qualify the boundaries of the trade space, identify performance envelopes, and understand advantages and limiting factors of designing for maximum payload capability. Using the NASA/DARPA Horizontal Launch Study (HLS) Point Design 2 (PD-2) as a point-of-departure configuration, two independent design actions were undertaken. Both configurations utilized a Boeing 747-400F as the carrier aircraft, LOX/RP-1 first stage and LOX/LH2 second stage. Each design was sized to meet dimensional and mass constraints while optimizing propellant loads and stage delta V (?V) splits. All concepts, when fully loaded, exceeded the allowable Gross Takeoff Weight (GTOW) of the aircraft platform. This excess mass was evaluated as propellant/fuel offload available for a potential in-flight refueling scenario. Results indicate many advantages such as large, relative payload delivery of approximately 47,000 lbm and significant mission flexibility, such as variable launch site inclination and launch window; however, in-flight cryogenic fluid transfer and carrier aircraft platform integration are substantial technical hurdles to the realization of such a system configuration.

  11. TRPM4 non-selective cation channels influence action potentials in rabbit Purkinje fibres.

    PubMed

    Hof, Thomas; Sallé, Laurent; Coulbault, Laurent; Richer, Romain; Alexandre, Joachim; Rouet, René; Manrique, Alain; Guinamard, Romain

    2016-01-15

    The transient receptor potential melastatin 4 (TRPM4) inhibitor 9-phenanthrol reduces action potential duration in rabbit Purkinje fibres but not in ventricle. TRPM4-like single channel activity is observed in isolated rabbit Purkinje cells but not in ventricular cells. The TRPM4-like current develops during the notch and early repolarization phases of the action potential in Purkinje cells. Transient receptor potential melastatin 4 (TRPM4) Ca(2+)-activated non-selective cation channel activity has been recorded in cardiomyocytes and sinus node cells from mammals. In addition, TRPM4 gene mutations are associated with human diseases of cardiac conduction, suggesting that TRPM4 plays a role in this aspect of cardiac function. Here we evaluate the TRPM4 contribution to cardiac electrophysiology of Purkinje fibres. Ventricular strips with Purkinje fibres were isolated from rabbit hearts. Intracellular microelectrodes recorded Purkinje fibre activity and the TRPM4 inhibitor 9-phenanthrol was applied to unmask potential TRPM4 contributions to the action potential. 9-Phenanthrol reduced action potential duration measured at the point of 50 and 90% repolarization with an EC50 of 32.8 and 36.1×10(-6) mol l(-1), respectively, but did not modulate ventricular action potentials. Inside-out patch-clamp recordings were used to monitor TRPM4 activity in isolated Purkinje cells. TRPM4-like single channel activity (conductance = 23.8 pS; equal permeability for Na(+) and K(+); sensitivity to voltage, Ca(2+) and 9-phenanthrol) was observed in 43% of patches from Purkinje cells but not from ventricular cells (0/16). Action potential clamp experiments performed in the whole-cell configuration revealed a transient inward 9-phenanthrol-sensitive current (peak density = -0.65 ± 0.15 pA pF(-1); n = 5) during the plateau phases of the Purkinje fibre action potential. These results show that TRPM4 influences action potential characteristics in rabbit Purkinje fibres and thus could modulate

  12. Air Launch: Examining Performance Potential of Various Configurations and Growth Options

    NASA Technical Reports Server (NTRS)

    Waters, Eric D.; Creech, Dennis M.; Philips, Alan D.

    2013-01-01

    The Advanced Concepts Office at NASA's George C. Marshall Space Flight Center conducted a high-level analysis of various air launch vehicle configurations, objectively determining maximum launch vehicle payload while considering carrier aircraft capabilities and given dimensional constraints. With the renewed interest in aerial launch of low-earth orbit payloads, referenced by programs such as Stratolaunch and Spaceship2, there exists a need to qualify the boundaries of the trade space, identify performance envelopes, and understand advantages and limiting factors of designing for maximum payload capability. Using the NASA/DARPA Horizontal Launch Study (HLS) Point Design 2 (PD-2) as a pointof- departure configuration, two independent design actions were undertaken. Both designs utilized a Boeing 747-400F as the carrier aircraft, LOX/RP-1 first stage and LOX/LH2 second stage. Each design was sized to meet dimensional and mass constraints while optimizing propellant loads and stage delta V splits. All concepts, when fully loaded, exceeded the allowable Gross Takeoff Weight (GTOW) of the aircraft platform. This excess mass was evaluated as propellant/fuel offload available for a potential in-flight propellant loading scenario. Results indicate many advantages such as payload delivery of approximately 47,000 lbm and significant mission flexibility including variable launch site inclination and launch window. However, in-flight cryogenic fluid transfer and carrier aircraft platform integration are substantial technical hurdles to the realization of such a system configuration.

  13. Mathematical modeling of shell configurations made of homogeneous and composite materials experiencing intensive short actions and large displacements

    NASA Astrophysics Data System (ADS)

    Khairnasov, K. Z.

    2018-04-01

    The paper presents a mathematical model for solving the problem of behavior of shell configurations under the action of static and dynamic impacts. The problem is solved in geometrically nonlinear statement with regard to the finite element method. The composite structures with different material layers are considered. The obtained equations are used to study the behavior of shell configurations under the action of dynamic loads. The results agree well with the experimental data.

  14. Effects of pioglitazone on cardiac ion currents and action potential morphology in canine ventricular myocytes.

    PubMed

    Kistamás, Kornél; Szentandrássy, Norbert; Hegyi, Bence; Ruzsnavszky, Ferenc; Váczi, Krisztina; Bárándi, László; Horváth, Balázs; Szebeni, Andrea; Magyar, János; Bányász, Tamás; Kecskeméti, Valéria; Nánási, Péter P

    2013-06-15

    Despite its widespread therapeutical use there is little information on the cellular cardiac effects of the antidiabetic drug pioglitazone in larger mammals. In the present study, therefore, the concentration-dependent effects of pioglitazone on ion currents and action potential configuration were studied in isolated canine ventricular myocytes using standard microelectrode, conventional whole cell patch clamp, and action potential voltage clamp techniques. Pioglitazone decreased the maximum velocity of depolarization and the amplitude of phase-1 repolarization at concentrations ≥3 μM. Action potentials were shortened by pioglitazone at concentrations ≥10 μM, which effect was accompanied with significant reduction of beat-to-beat variability of action potential duration. Several transmembrane ion currents, including the transient outward K(+) current (Ito), the L-type Ca(2+) current (ICa), the rapid and slow components of the delayed rectifier K(+) current (IKr and IKs, respectively), and the inward rectifier K(+) current (IK1) were inhibited by pioglitazone under conventional voltage clamp conditions. Ito was blocked significantly at concentrations ≥3 μM, ICa, IKr, IKs at concentrations ≥10 μM, while IK1 at concentrations ≥30 μM. Suppression of Ito, ICa, IKr, and IK1 has been confirmed also under action potential voltage clamp conditions. ATP-sensitive K(+) current, when activated by lemakalim, was effectively blocked by pioglitazone. Accordingly, action potentials were prolonged by 10 μM pioglitazone when the drug was applied in the presence of lemakalim. All these effects developed rapidly and were readily reversible upon washout. In conclusion, pioglitazone seems to be a harmless agent at usual therapeutic concentrations. Copyright © 2013 Elsevier B.V. All rights reserved.

  15. Simulation of action potential propagation in plants.

    PubMed

    Sukhov, Vladimir; Nerush, Vladimir; Orlova, Lyubov; Vodeneev, Vladimir

    2011-12-21

    Action potential is considered to be one of the primary responses of a plant to action of various environmental factors. Understanding plant action potential propagation mechanisms requires experimental investigation and simulation; however, a detailed mathematical model of plant electrical signal transmission is absent. Here, the mathematical model of action potential propagation in plants has been worked out. The model is a two-dimensional system of excitable cells; each of them is electrically coupled with four neighboring ones. Ion diffusion between excitable cell apoplast areas is also taken into account. The action potential generation in a single cell has been described on the basis of our previous model. The model simulates active and passive signal transmission well enough. It has been used to analyze theoretically the influence of cell to cell electrical conductivity and H(+)-ATPase activity on the signal transmission in plants. An increase in cell to cell electrical conductivity has been shown to stimulate an increase in the length constant, the action potential propagation velocity and the temperature threshold, while the membrane potential threshold being weakly changed. The growth of H(+)-ATPase activity has been found to induce the increase of temperature and membrane potential thresholds and the reduction of the length constant and the action potential propagation velocity. Copyright © 2011 Elsevier Ltd. All rights reserved.

  16. Action potentials reliably invade axonal arbors of rat neocortical neurons

    PubMed Central

    Cox, Charles L.; Denk, Winfried; Tank, David W.; Svoboda, Karel

    2000-01-01

    Neocortical pyramidal neurons have extensive axonal arborizations that make thousands of synapses. Action potentials can invade these arbors and cause calcium influx that is required for neurotransmitter release and excitation of postsynaptic targets. Thus, the regulation of action potential invasion in axonal branches might shape the spread of excitation in cortical neural networks. To measure the reliability and extent of action potential invasion into axonal arbors, we have used two-photon excitation laser scanning microscopy to directly image action-potential-mediated calcium influx in single varicosities of layer 2/3 pyramidal neurons in acute brain slices. Our data show that single action potentials or bursts of action potentials reliably invade axonal arbors over a range of developmental ages (postnatal 10–24 days) and temperatures (24°C-30°C). Hyperpolarizing current steps preceding action potential initiation, protocols that had previously been observed to produce failures of action potential propagation in cultured preparations, were ineffective in modulating the spread of action potentials in acute slices. Our data show that action potentials reliably invade the axonal arbors of neocortical pyramidal neurons. Failures in synaptic transmission must therefore originate downstream of action potential invasion. We also explored the function of modulators that inhibit presynaptic calcium influx. Consistent with previous studies, we find that adenosine reduces action-potential-mediated calcium influx in presynaptic terminals. This reduction was observed in all terminals tested, suggesting that some modulatory systems are expressed homogeneously in most terminals of the same neuron. PMID:10931955

  17. Intracellular recording of action potentials by nanopillar electroporation.

    PubMed

    Xie, Chong; Lin, Ziliang; Hanson, Lindsey; Cui, Yi; Cui, Bianxiao

    2012-02-12

    Action potentials have a central role in the nervous system and in many cellular processes, notably those involving ion channels. The accurate measurement of action potentials requires efficient coupling between the cell membrane and the measuring electrodes. Intracellular recording methods such as patch clamping involve measuring the voltage or current across the cell membrane by accessing the cell interior with an electrode, allowing both the amplitude and shape of the action potentials to be recorded faithfully with high signal-to-noise ratios. However, the invasive nature of intracellular methods usually limits the recording time to a few hours, and their complexity makes it difficult to simultaneously record more than a few cells. Extracellular recording methods, such as multielectrode arrays and multitransistor arrays, are non-invasive and allow long-term and multiplexed measurements. However, extracellular recording sacrifices the one-to-one correspondence between the cells and electrodes, and also suffers from significantly reduced signal strength and quality. Extracellular techniques are not, therefore, able to record action potentials with the accuracy needed to explore the properties of ion channels. As a result, the pharmacological screening of ion-channel drugs is usually performed by low-throughput intracellular recording methods. The use of nanowire transistors, nanotube-coupled transistors and micro gold-spine and related electrodes can significantly improve the signal strength of recorded action potentials. Here, we show that vertical nanopillar electrodes can record both the extracellular and intracellular action potentials of cultured cardiomyocytes over a long period of time with excellent signal strength and quality. Moreover, it is possible to repeatedly switch between extracellular and intracellular recording by nanoscale electroporation and resealing processes. Furthermore, vertical nanopillar electrodes can detect subtle changes in action

  18. Intracellular recording of action potentials by nanopillar electroporation

    NASA Astrophysics Data System (ADS)

    Xie, Chong; Lin, Ziliang; Hanson, Lindsey; Cui, Yi; Cui, Bianxiao

    2012-03-01

    Action potentials have a central role in the nervous system and in many cellular processes, notably those involving ion channels. The accurate measurement of action potentials requires efficient coupling between the cell membrane and the measuring electrodes. Intracellular recording methods such as patch clamping involve measuring the voltage or current across the cell membrane by accessing the cell interior with an electrode, allowing both the amplitude and shape of the action potentials to be recorded faithfully with high signal-to-noise ratios. However, the invasive nature of intracellular methods usually limits the recording time to a few hours, and their complexity makes it difficult to simultaneously record more than a few cells. Extracellular recording methods, such as multielectrode arrays and multitransistor arrays, are non-invasive and allow long-term and multiplexed measurements. However, extracellular recording sacrifices the one-to-one correspondence between the cells and electrodes, and also suffers from significantly reduced signal strength and quality. Extracellular techniques are not, therefore, able to record action potentials with the accuracy needed to explore the properties of ion channels. As a result, the pharmacological screening of ion-channel drugs is usually performed by low-throughput intracellular recording methods. The use of nanowire transistors, nanotube-coupled transistors and micro gold-spine and related electrodes can significantly improve the signal strength of recorded action potentials. Here, we show that vertical nanopillar electrodes can record both the extracellular and intracellular action potentials of cultured cardiomyocytes over a long period of time with excellent signal strength and quality. Moreover, it is possible to repeatedly switch between extracellular and intracellular recording by nanoscale electroporation and resealing processes. Furthermore, vertical nanopillar electrodes can detect subtle changes in action

  19. Optical mapping of optogenetically shaped cardiac action potentials.

    PubMed

    Park, Sarah A; Lee, Shin-Rong; Tung, Leslie; Yue, David T

    2014-08-19

    Light-mediated silencing and stimulation of cardiac excitability, an important complement to electrical stimulation, promises important discoveries and therapies. To date, cardiac optogenetics has been studied with patch-clamp, multielectrode arrays, video microscopy, and an all-optical system measuring calcium transients. The future lies in achieving simultaneous optical acquisition of excitability signals and optogenetic control, both with high spatio-temporal resolution. Here, we make progress by combining optical mapping of action potentials with concurrent activation of channelrhodopsin-2 (ChR2) or halorhodopsin (eNpHR3.0), via an all-optical system applied to monolayers of neonatal rat ventricular myocytes (NRVM). Additionally, we explore the capability of ChR2 and eNpHR3.0 to shape action-potential waveforms, potentially aiding the study of short/long QT syndromes that result from abnormal changes in action potential duration (APD). These results show the promise of an all-optical system to acquire action potentials with precise temporal optogenetics control, achieving a long-sought flexibility beyond the means of conventional electrical stimulation.

  20. Optical mapping of optogenetically shaped cardiac action potentials

    PubMed Central

    Park, Sarah A.; Lee, Shin-Rong; Tung, Leslie; Yue, David T.

    2014-01-01

    Light-mediated silencing and stimulation of cardiac excitability, an important complement to electrical stimulation, promises important discoveries and therapies. To date, cardiac optogenetics has been studied with patch-clamp, multielectrode arrays, video microscopy, and an all-optical system measuring calcium transients. The future lies in achieving simultaneous optical acquisition of excitability signals and optogenetic control, both with high spatio-temporal resolution. Here, we make progress by combining optical mapping of action potentials with concurrent activation of channelrhodopsin-2 (ChR2) or halorhodopsin (eNpHR3.0), via an all-optical system applied to monolayers of neonatal rat ventricular myocytes (NRVM). Additionally, we explore the capability of ChR2 and eNpHR3.0 to shape action-potential waveforms, potentially aiding the study of short/long QT syndromes that result from abnormal changes in action potential duration (APD). These results show the promise of an all-optical system to acquire action potentials with precise temporal optogenetics control, achieving a long-sought flexibility beyond the means of conventional electrical stimulation. PMID:25135113

  1. Action potential propagation: ion current or intramembrane electric field?

    PubMed

    Martí, Albert; Pérez, Juan J; Madrenas, Jordi

    2018-01-01

    The established action potential propagation mechanisms do not satisfactorily explain propagation on myelinated axons given the current knowledge of biological channels and membranes. The flow across ion channels presents two possible effects: the electric potential variations across the lipid bilayers (action potential) and the propagation of an electric field through the membrane inner part. The proposed mechanism is based on intra-membrane electric field propagation, this propagation can explain the action potential saltatory propagation and its constant delay independent of distance between Ranvier nodes in myelinated axons.

  2. Selective effects of an octopus toxin on action potentials

    PubMed Central

    Dulhunty, Angela; Gage, Peter W.

    1971-01-01

    1. A lethal, water soluble toxin (Maculotoxin, MTX) with a molecular weight less than 540, can be extracted from the salivary glands of an octopus (Hapalochlaena maculosa). 2. MTX blocks action potentials in sartorius muscle fibres of toads without affecting the membrane potential. Delayed rectification is not inhibited by the toxin. 3. At low concentrations (10-6-10-5 g/ml.) MTX blocks action potentials only after a certain number have been elicited. The number of action potentials, which can be defined accurately, depends on the concentration of MTX and the concentration of sodium ions in the extracellular solution. 4. The toxin has no post-synaptic effect at the neuromuscular junction and it is concluded that it blocks neuromuscular transmission by inhibiting action potentials in motor nerve terminals. PMID:4330930

  3. Potential for Landing Gear Noise Reduction on Advanced Aircraft Configurations

    NASA Technical Reports Server (NTRS)

    Thomas, Russell H.; Nickol, Craig L.; Burley, Casey L.; Guo, Yueping

    2016-01-01

    The potential of significantly reducing aircraft landing gear noise is explored for aircraft configurations with engines installed above the wings or the fuselage. An innovative concept is studied that does not alter the main gear assembly itself but does shorten the main strut and integrates the gear in pods whose interior surfaces are treated with acoustic liner. The concept is meant to achieve maximum noise reduction so that main landing gears can be eliminated as a major source of airframe noise. By applying this concept to an aircraft configuration with 2025 entry-into-service technology levels, it is shown that compared to noise levels of current technology, the main gear noise can be reduced by 10 EPNL dB, bringing the main gear noise close to a floor established by other components such as the nose gear. The assessment of the noise reduction potential accounts for design features for the advanced aircraft configuration and includes the effects of local flow velocity in and around the pods, gear noise reflection from the airframe, and reflection and attenuation from acoustic liner treatment on pod surfaces and doors. A technical roadmap for maturing this concept is discussed, and the possible drag increase at cruise due to the addition of the pods is identified as a challenge, which needs to be quantified and minimized possibly with the combination of detailed design and application of drag reduction technologies.

  4. Short infrared laser pulses block action potentials in neurons

    NASA Astrophysics Data System (ADS)

    Walsh, Alex J.; Tolstykh, Gleb P.; Martens, Stacey L.; Ibey, Bennett L.; Beier, Hope T.

    2017-02-01

    Short infrared laser pulses have many physiological effects on cells including the ability to stimulate action potentials in neurons. Here we show that short infrared laser pulses can also reversibly block action potentials. Primary rat hippocampal neurons were transfected with the Optopatch2 plasmid, which contains both a blue-light activated channel rhodopsin (CheRiff) and a red-light fluorescent membrane voltage reporter (QuasAr2). This optogenetic platform allows robust stimulation and recording of action potential activity in neurons in a non-contact, low noise manner. For all experiments, QuasAr2 was imaged continuously on a wide-field fluorescent microscope using a Krypton laser (647 nm) as the excitation source and an EMCCD camera operating at 1000 Hz to collect emitted fluorescence. A co-aligned Argon laser (488 nm, 5 ms at 10Hz) provided activation light for CheRiff. A 200 mm fiber delivered infrared light locally to the target neuron. Reversible action potential block in neurons was observed following a short infrared laser pulse (0.26-0.96 J/cm2; 1.37-5.01 ms; 1869 nm), with the block persisting for more than 1 s with exposures greater than 0.69 J/cm2. Action potential block was sustained for 30 s with the short infrared laser pulsed at 1-7 Hz. Full recovery of neuronal activity was observed 5-30s post-infrared exposure. These results indicate that optogenetics provides a robust platform for the study of action potential block and that short infrared laser pulses can be used for non-contact, reversible action potential block.

  5. Quadratic adaptive algorithm for solving cardiac action potential models.

    PubMed

    Chen, Min-Hung; Chen, Po-Yuan; Luo, Ching-Hsing

    2016-10-01

    An adaptive integration method is proposed for computing cardiac action potential models accurately and efficiently. Time steps are adaptively chosen by solving a quadratic formula involving the first and second derivatives of the membrane action potential. To improve the numerical accuracy, we devise an extremum-locator (el) function to predict the local extremum when approaching the peak amplitude of the action potential. In addition, the time step restriction (tsr) technique is designed to limit the increase in time steps, and thus prevent the membrane potential from changing abruptly. The performance of the proposed method is tested using the Luo-Rudy phase 1 (LR1), dynamic (LR2), and human O'Hara-Rudy dynamic (ORd) ventricular action potential models, and the Courtemanche atrial model incorporating a Markov sodium channel model. Numerical experiments demonstrate that the action potential generated using the proposed method is more accurate than that using the traditional Hybrid method, especially near the peak region. The traditional Hybrid method may choose large time steps near to the peak region, and sometimes causes the action potential to become distorted. In contrast, the proposed new method chooses very fine time steps in the peak region, but large time steps in the smooth region, and the profiles are smoother and closer to the reference solution. In the test on the stiff Markov ionic channel model, the Hybrid blows up if the allowable time step is set to be greater than 0.1ms. In contrast, our method can adjust the time step size automatically, and is stable. Overall, the proposed method is more accurate than and as efficient as the traditional Hybrid method, especially for the human ORd model. The proposed method shows improvement for action potentials with a non-smooth morphology, and it needs further investigation to determine whether the method is helpful during propagation of the action potential. Copyright © 2016 Elsevier Ltd. All rights

  6. Decision making and action implementation: evidence for an early visually triggered motor activation specific to potential actions.

    PubMed

    Tandonnet, Christophe; Garry, Michael I; Summers, Jeffery J

    2013-07-01

    To make a decision may rely on accumulating evidence in favor of one alternative until a threshold is reached. Sequential-sampling models differ by the way of accumulating evidence and the link with action implementation. Here, we tested a model's prediction of an early action implementation specific to potential actions. We assessed the dynamics of action implementation in go/no-go and between-hand choice tasks by transcranial magnetic stimulation of the motor cortex (single- or paired-pulse TMS; 3-ms interstimulus interval). Prior to implementation of the selected action, the amplitude of the motor evoked potential first increased whatever the visual stimulus but only for the hand potentially involved in the to-be-produced action. These findings suggest that visual stimuli can trigger an early motor activation specific to potential actions, consistent with race-like models with continuous transmission between decision making and action implementation. Copyright © 2013 Society for Psychophysiological Research.

  7. Synchronization of action potentials during low-magnesium-induced bursting

    PubMed Central

    Johnson, Sarah E.; Hudson, John L.

    2015-01-01

    The relationship between mono- and polysynaptic strength and action potential synchronization was explored using a reduced external Mg2+ model. Single and dual whole cell patch-clamp recordings were performed in hippocampal cultures in three concentrations of external Mg2+. In decreased Mg2+ medium, the individual cells transitioned to spontaneous bursting behavior. In lowered Mg2+ media the larger excitatory synaptic events were observed more frequently and fewer transmission failures occurred, suggesting strengthened synaptic transmission. The event synchronization was calculated for the neural action potentials of the cell pairs, and it increased in media where Mg2+ concentration was lowered. Analysis of surrogate data where bursting was present, but no direct or indirect connections existed between the neurons, showed minimal action potential synchronization. This suggests the synchronization of action potentials is a product of the strengthening synaptic connections within neuronal networks. PMID:25609103

  8. Synchronization of action potentials during low-magnesium-induced bursting.

    PubMed

    Johnson, Sarah E; Hudson, John L; Kapur, Jaideep

    2015-04-01

    The relationship between mono- and polysynaptic strength and action potential synchronization was explored using a reduced external Mg(2+) model. Single and dual whole cell patch-clamp recordings were performed in hippocampal cultures in three concentrations of external Mg(2+). In decreased Mg(2+) medium, the individual cells transitioned to spontaneous bursting behavior. In lowered Mg(2+) media the larger excitatory synaptic events were observed more frequently and fewer transmission failures occurred, suggesting strengthened synaptic transmission. The event synchronization was calculated for the neural action potentials of the cell pairs, and it increased in media where Mg(2+) concentration was lowered. Analysis of surrogate data where bursting was present, but no direct or indirect connections existed between the neurons, showed minimal action potential synchronization. This suggests the synchronization of action potentials is a product of the strengthening synaptic connections within neuronal networks. Copyright © 2015 the American Physiological Society.

  9. Redetermined structure, inter-molecular inter-actions and absolute configuration of royleanone.

    PubMed

    Fun, Hoong-Kun; Chantrapromma, Suchada; Salae, Abdul Wahab; Razak, Ibrahim Abdul; Karalai, Chatchanok

    2011-05-01

    The structure of the title diterpenoid, C(20)H(28)O(3), {systematic name: (4bS,8aS)-3-hy-droxy-2-isopropyl-4b,8,8-trimethyl-4b,5,6,7,8,8a,9,10-octa-hydro-phenanthrene-1,4-dione} is confirmed [Eugster et al. (1993 ▶). Private communication (refcode HACGUN). CCDC, Union Road, Cambridge] and its packing is now described. Its absolute structure was established by refinement against data collected with Cu radiation: the two stereogenic centres both have S configurations. One cyclo-hexane ring adopts a chair conformation whereas the other cyclo-hexane ring is in a half-chair conformation and the benzoquinone ring is slightly twisted. An intra-molecular O-H⋯O hydrogen bond generates an S(5) ring motif. In the crystal, mol-ecules are linked into chains along [010] by O-H⋯O hydrogen bonds and weak C-H⋯O inter-actions. The packing also features C⋯O [3.131 (3) Å] short contacts.

  10. Tank waste remediation system configuration management implementation plan

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Vann, J.M.

    1998-03-31

    The Tank Waste Remediation System (TWRS) Configuration Management Implementation Plan describes the actions that will be taken by Project Hanford Management Contract Team to implement the TWRS Configuration Management program defined in HNF 1900, TWRS Configuration Management Plan. Over the next 25 years, the TWRS Project will transition from a safe storage mission to an aggressive retrieval, storage, and disposal mission in which substantial Engineering, Construction, and Operations activities must be performed. This mission, as defined, will require a consolidated configuration management approach to engineering, design, construction, as-building, and operating in accordance with the technical baselines that emerge from themore » life cycles. This Configuration Management Implementation Plan addresses the actions that will be taken to strengthen the TWRS Configuration Management program.« less

  11. Components of action potential repolarization in cerebellar parallel fibres.

    PubMed

    Pekala, Dobromila; Baginskas, Armantas; Szkudlarek, Hanna J; Raastad, Morten

    2014-11-15

    Repolarization of the presynaptic action potential is essential for transmitter release, excitability and energy expenditure. Little is known about repolarization in thin, unmyelinated axons forming en passant synapses, which represent the most common type of axons in the mammalian brain's grey matter.We used rat cerebellar parallel fibres, an example of typical grey matter axons, to investigate the effects of K(+) channel blockers on repolarization. We show that repolarization is composed of a fast tetraethylammonium (TEA)-sensitive component, determining the width and amplitude of the spike, and a slow margatoxin (MgTX)-sensitive depolarized after-potential (DAP). These two components could be recorded at the granule cell soma as antidromic action potentials and from the axons with a newly developed miniaturized grease-gap method. A considerable proportion of fast repolarization remained in the presence of TEA, MgTX, or both. This residual was abolished by the addition of quinine. The importance of proper control of fast repolarization was demonstrated by somatic recordings of antidromic action potentials. In these experiments, the relatively broad K(+) channel blocker 4-aminopyridine reduced the fast repolarization, resulting in bursts of action potentials forming on top of the DAP. We conclude that repolarization of the action potential in parallel fibres is supported by at least three groups of K(+) channels. Differences in their temporal profiles allow relatively independent control of the spike and the DAP, whereas overlap of their temporal profiles provides robust control of axonal bursting properties.

  12. Spontaneous action potentials and neural coding in unmyelinated axons.

    PubMed

    O'Donnell, Cian; van Rossum, Mark C W

    2015-04-01

    The voltage-gated Na and K channels in neurons are responsible for action potential generation. Because ion channels open and close in a stochastic fashion, spontaneous (ectopic) action potentials can result even in the absence of stimulation. While spontaneous action potentials have been studied in detail in single-compartment models, studies on spatially extended processes have been limited. The simulations and analysis presented here show that spontaneous rate in unmyelinated axon depends nonmonotonically on the length of the axon, that the spontaneous activity has sub-Poisson statistics, and that neural coding can be hampered by the spontaneous spikes by reducing the probability of transmitting the first spike in a train.

  13. Three-dimensional transonic potential flow about complex 3-dimensional configurations

    NASA Technical Reports Server (NTRS)

    Reyhner, T. A.

    1984-01-01

    An analysis has been developed and a computer code written to predict three-dimensional subsonic or transonic potential flow fields about lifting or nonlifting configurations. Possible condfigurations include inlets, nacelles, nacelles with ground planes, S-ducts, turboprop nacelles, wings, and wing-pylon-nacelle combinations. The solution of the full partial differential equation for compressible potential flow written in terms of a velocity potential is obtained using finite differences, line relaxation, and multigrid. The analysis uses either a cylindrical or Cartesian coordinate system. The computational mesh is not body fitted. The analysis has been programmed in FORTRAN for both the CDC CYBER 203 and the CRAY-1 computers. Comparisons of computed results with experimental measurement are presented. Descriptions of the program input and output formats are included.

  14. [Loudness optimized registration of compound action potential in cochlear implant recipients].

    PubMed

    Berger, Klaus; Hocke, Thomas; Hessel, Horst

    2017-11-01

    Background Postoperative measurements of compound action potentials are not always possible due to the insufficient acceptance of the CI-recipients. This study investigated the impact of different parameters on the acceptance of the measurements. Methods Compound action potentials of 16 CI recipients were measured with different pulse-widths. Recipients performed a loudness rating at the potential thresholds with the different sequences. Results Compound action potentials obtained with higher pulse-widths were rated softer than those obtained with smaller pulse-widths. Conclusions Compound action potentials measured with higher pulse-widths generate a gap between loudest acceptable presentation level and potential threshold. This gap contributes to a higher acceptance of postoperative measurements. Georg Thieme Verlag KG Stuttgart · New York.

  15. Potentialities of a new sigma(+)-sigma(-)laser configuration for radiative cooling and trapping

    NASA Astrophysics Data System (ADS)

    Dalibard, J.; Reynaud, S.; Cohen-Tannoudji, C.

    1984-11-01

    In the process of cooling and trapping neutral atoms, a new laser configuration is investigated which consists of two counterpropagating laser beams with orthogonal sigma(+) and sigma(-)polarizations. It is shown that such a configuration looks more promising than an ordinary standing wave (where the two counterpropagating waves have the same polarization), and this result is explained as being due to angular momentum conservation which prevents any coherent redistribution of photons between the two waves. The present conclusions are based on a quantitative calculation of the various parameters (potential depth, friction coefficient, diffusion coefficient) describing the mean value and the fluctuations of the radiative forces experienced, in such a laser configuration, by an atom with a J = 0 ground state and a J = 1 excited state.

  16. Aerodynamic analysis of three advanced configurations using the TranAir full-potential code

    NASA Technical Reports Server (NTRS)

    Madson, M. D.; Carmichael, R. L.; Mendoza, J. P.

    1989-01-01

    Computational results are presented for three advanced configurations: the F-16A with wing tip missiles and under wing fuel tanks, the Oblique Wing Research Aircraft, and an Advanced Turboprop research model. These results were generated by the latest version of the TranAir full potential code, which solves for transonic flow over complex configurations. TranAir embeds a surface paneled geometry definition in a uniform rectangular flow field grid, thus avoiding the use of surface conforming grids, and decoupling the grid generation process from the definition of the configuration. The new version of the code locally refines the uniform grid near the surface of the geometry, based on local panel size and/or user input. This method distributes the flow field grid points much more efficiently than the previous version of the code, which solved for a grid that was uniform everywhere in the flow field. TranAir results are presented for the three configurations and are compared with wind tunnel data.

  17. Intracellular recordings of action potentials by an extracellular nanoscale field-effect transistor.

    PubMed

    Duan, Xiaojie; Gao, Ruixuan; Xie, Ping; Cohen-Karni, Tzahi; Qing, Quan; Choe, Hwan Sung; Tian, Bozhi; Jiang, Xiaocheng; Lieber, Charles M

    2011-12-18

    The ability to make electrical measurements inside cells has led to many important advances in electrophysiology. The patch clamp technique, in which a glass micropipette filled with electrolyte is inserted into a cell, offers both high signal-to-noise ratio and temporal resolution. Ideally, the micropipette should be as small as possible to increase the spatial resolution and reduce the invasiveness of the measurement, but the overall performance of the technique depends on the impedance of the interface between the micropipette and the cell interior, which limits how small the micropipette can be. Techniques that involve inserting metal or carbon microelectrodes into cells are subject to similar constraints. Field-effect transistors (FETs) can also record electric potentials inside cells, and because their performance does not depend on impedance, they can be made much smaller than micropipettes and microelectrodes. Moreover, FET arrays are better suited for multiplexed measurements. Previously, we have demonstrated FET-based intracellular recording with kinked nanowire structures, but the kink configuration and device design places limits on the probe size and the potential for multiplexing. Here, we report a new approach in which a SiO2 nanotube is synthetically integrated on top of a nanoscale FET. This nanotube penetrates the cell membrane, bringing the cell cytosol into contact with the FET, which is then able to record the intracellular transmembrane potential. Simulations show that the bandwidth of this branched intracellular nanotube FET (BIT-FET) is high enough for it to record fast action potentials even when the nanotube diameter is decreased to 3 nm, a length scale well below that accessible with other methods. Studies of cardiomyocyte cells demonstrate that when phospholipid-modified BIT-FETs are brought close to cells, the nanotubes can spontaneously penetrate the cell membrane to allow the full-amplitude intracellular action potential to be

  18. Intracellular recordings of action potentials by an extracellular nanoscale field-effect transistor

    NASA Astrophysics Data System (ADS)

    Duan, Xiaojie; Gao, Ruixuan; Xie, Ping; Cohen-Karni, Tzahi; Qing, Quan; Choe, Hwan Sung; Tian, Bozhi; Jiang, Xiaocheng; Lieber, Charles M.

    2012-03-01

    The ability to make electrical measurements inside cells has led to many important advances in electrophysiology. The patch clamp technique, in which a glass micropipette filled with electrolyte is inserted into a cell, offers both high signal-to-noise ratio and temporal resolution. Ideally, the micropipette should be as small as possible to increase the spatial resolution and reduce the invasiveness of the measurement, but the overall performance of the technique depends on the impedance of the interface between the micropipette and the cell interior, which limits how small the micropipette can be. Techniques that involve inserting metal or carbon microelectrodes into cells are subject to similar constraints. Field-effect transistors (FETs) can also record electric potentials inside cells, and because their performance does not depend on impedance, they can be made much smaller than micropipettes and microelectrodes. Moreover, FET arrays are better suited for multiplexed measurements. Previously, we have demonstrated FET-based intracellular recording with kinked nanowire structures, but the kink configuration and device design places limits on the probe size and the potential for multiplexing. Here, we report a new approach in which a SiO2 nanotube is synthetically integrated on top of a nanoscale FET. This nanotube penetrates the cell membrane, bringing the cell cytosol into contact with the FET, which is then able to record the intracellular transmembrane potential. Simulations show that the bandwidth of this branched intracellular nanotube FET (BIT-FET) is high enough for it to record fast action potentials even when the nanotube diameter is decreased to 3 nm, a length scale well below that accessible with other methods. Studies of cardiomyocyte cells demonstrate that when phospholipid-modified BIT-FETs are brought close to cells, the nanotubes can spontaneously penetrate the cell membrane to allow the full-amplitude intracellular action potential to be

  19. Antidromic propagation of action potentials in branched axons: implications for the mechanisms of action of deep brain stimulation.

    PubMed

    Grill, Warren M; Cantrell, Meredith B; Robertson, Matthew S

    2008-02-01

    Electrical stimulation of the central nervous system creates both orthodromically propagating action potentials, by stimulation of local cells and passing axons, and antidromically propagating action potentials, by stimulation of presynaptic axons and terminals. Our aim was to understand how antidromic action potentials navigate through complex arborizations, such as those of thalamic and basal ganglia afferents-sites of electrical activation during deep brain stimulation. We developed computational models to study the propagation of antidromic action potentials past the bifurcation in branched axons. In both unmyelinated and myelinated branched axons, when the diameters of each axon branch remained under a specific threshold (set by the antidromic geometric ratio), antidromic propagation occurred robustly; action potentials traveled both antidromically into the primary segment as well as "re-orthodromically" into the terminal secondary segment. Propagation occurred across a broad range of stimulation frequencies, axon segment geometries, and concentrations of extracellular potassium, but was strongly dependent on the geometry of the node of Ranvier at the axonal bifurcation. Thus, antidromic activation of axon terminals can, through axon collaterals, lead to widespread activation or inhibition of targets remote from the site of stimulation. These effects should be included when interpreting the results of functional imaging or evoked potential studies on the mechanisms of action of DBS.

  20. The role of Na-Ca exchange current in the cardiac action potential.

    PubMed

    Janvier, N C; Boyett, M R

    1996-07-01

    Since 1981, when Mullins published his provocative book proposing that the Na-Ca exchanger is electrogenic, it has been shown, first by computer simulation by Noble and later by experiment by various investigators, that inward iNaCa triggered by the Ca2+ transient is responsible for the low plateau of the atrial action potential and contributes to the high plateau of the ventricular action potential. Reduction or complete block of inward iNaCa by buffering intracellular Ca2+ with EGTA or BAPTA, by blocking SR Ca2+ release or by substituting extracellular Na+ with Li+ can result in a shortening of the action potential. The effect of block of outward iNaCa or complete block of both inward and outward iNaCa on the action potential has not been investigated experimentally, because of the lack of a suitable blocker, and remains a goal for the future. An increase in the intracellular Na+ concentration (after the application of cardiac glycoside or an increase in heart rate) or an increase in extracellular Ca2+ are believed to lead to an outward shift in iNaCa at plateau potentials and a shortening of the action potential. Changes in the Ca2+ transient are expected to result in changes in inward iNaCa and thus the action potential. This may explain the shortening of the premature action potential as well as the prolongation of the action potential when a muscle is allowed to shorten during the action potential. Inward iNaCa may play an important role in both normal and abnormal pacemaker activity in the heart.

  1. State and location dependence of action potential metabolic cost in cortical pyramidal neurons.

    PubMed

    Hallermann, Stefan; de Kock, Christiaan P J; Stuart, Greg J; Kole, Maarten H P

    2012-06-03

    Action potential generation and conduction requires large quantities of energy to restore Na(+) and K(+) ion gradients. We investigated the subcellular location and voltage dependence of this metabolic cost in rat neocortical pyramidal neurons. Using Na(+)/K(+) charge overlap as a measure of action potential energy efficiency, we found that action potential initiation in the axon initial segment (AIS) and forward propagation into the axon were energetically inefficient, depending on the resting membrane potential. In contrast, action potential backpropagation into dendrites was efficient. Computer simulations predicted that, although the AIS and nodes of Ranvier had the highest metabolic cost per membrane area, action potential backpropagation into the dendrites and forward propagation into axon collaterals dominated energy consumption in cortical pyramidal neurons. Finally, we found that the high metabolic cost of action potential initiation and propagation down the axon is a trade-off between energy minimization and maximization of the conduction reliability of high-frequency action potentials.

  2. Action Learning: Potential for Inner City Youth

    ERIC Educational Resources Information Center

    Epps, Edgar G.

    1974-01-01

    Working class and minority participation in action-learning poses potential problems likely to be overlooked by program planners. This presentation reveals the trouble spots and offers constructive suggestions. (Editor)

  3. Active action potential propagation but not initiation in thalamic interneuron dendrites

    PubMed Central

    Casale, Amanda E.; McCormick, David A.

    2012-01-01

    Inhibitory interneurons of the dorsal lateral geniculate nucleus of the thalamus modulate the activity of thalamocortical cells in response to excitatory input through the release of inhibitory neurotransmitter from both axons and dendrites. The exact mechanisms by which release can occur from dendrites are, however, not well understood. Recent experiments using calcium imaging have suggested that Na/K based action potentials can evoke calcium transients in dendrites via local active conductances, making the back-propagating action potential a candidate for dendritic neurotransmitter release. In this study, we employed high temporal and spatial resolution voltage-sensitive dye imaging to assess the characteristics of dendritic voltage deflections in response to Na/K action potentials in interneurons of the mouse dorsal lateral geniculate nucleus. We found that trains or single action potentials elicited by somatic current injection or local synaptic stimulation led to action potentials that rapidly and actively back-propagated throughout the entire dendritic arbor and into the fine filiform dendritic appendages known to release GABAergic vesicles. Action potentials always appeared first in the soma or proximal dendrite in response to somatic current injection or local synaptic stimulation, and the rapid back-propagation into the dendritic arbor depended upon voltage-gated sodium and TEA-sensitive potassium channels. Our results indicate that thalamic interneuron dendrites integrate synaptic inputs that initiate action potentials, most likely in the axon initial segment, that then back-propagate with high-fidelity into the dendrites, resulting in a nearly synchronous release of GABA from both axonal and dendritic compartments. PMID:22171033

  4. Detachable glass microelectrodes for recording action potentials in active moving organs.

    PubMed

    Barbic, Mladen; Moreno, Angel; Harris, Tim D; Kay, Matthew W

    2017-06-01

    Here, we describe new detachable floating glass micropipette electrode devices that provide targeted action potential recordings in active moving organs without requiring constant mechanical constraint or pharmacological inhibition of tissue motion. The technology is based on the concept of a glass micropipette electrode that is held firmly during cell targeting and intracellular insertion, after which a 100-µg glass microelectrode, a "microdevice," is gently released to remain within the moving organ. The microdevices provide long-term recordings of action potentials, even during millimeter-scale movement of tissue in which the device is embedded. We demonstrate two different glass micropipette electrode holding and detachment designs appropriate for the heart (sharp glass microdevices for cardiac myocytes in rats, guinea pigs, and humans) and the brain (patch glass microdevices for neurons in rats). We explain how microdevices enable measurements of multiple cells within a moving organ that are typically difficult with other technologies. Using sharp microdevices, action potential duration was monitored continuously for 15 min in unconstrained perfused hearts during global ischemia-reperfusion, providing beat-to-beat measurements of changes in action potential duration. Action potentials from neurons in the hippocampus of anesthetized rats were measured with patch microdevices, which provided stable base potentials during long-term recordings. Our results demonstrate that detachable microdevices are an elegant and robust tool to record electrical activity with high temporal resolution and cellular level localization without disturbing the physiological working conditions of the organ. NEW & NOTEWORTHY Cellular action potential measurements within tissue using glass micropipette electrodes usually require tissue immobilization, potentially influencing the physiological relevance of the measurement. Here, we addressed this limitation with novel 100-µg detachable

  5. [Effect of pulse magnetic field on distribution of neuronal action potential].

    PubMed

    Zheng, Yu; Cai, Di; Wang, Jin-Hai; Li, Gang; Lin, Ling

    2014-08-25

    The biological effect on the organism generated by magnetic field is widely studied. The present study was aimed to observe the change of sodium channel under magnetic field in neurons. Cortical neurons of Kunming mice were isolated, subjected to 15 Hz, 1 mT pulse magnetic stimulation, and then the currents of neurons were recorded by whole-cell patch clamp. The results showed that, under magnetic stimulation, the activation process of Na(+) channel was delayed, and the inactivation process was accelerated. Given the classic three-layer model, the polarization diagram of cell membrane potential distribution under pulse magnetic field was simulated, and it was found that the membrane potential induced was associated with the frequency and intensity of magnetic field. Also the effect of magnetic field-induced current on action potential was simulated by Hodgkin-Huxley (H-H) model. The result showed that the generation of action potential was delayed, and frequency and the amplitudes were decreased when working current was between -1.32 μA and 0 μA. When the working current was higher than 0 μA, the generation frequency of action potential was increased, and the change of amplitudes was not obvious, and when the working current was lower than -1.32 μA, the time of rising edge and amplitudes of action potential were decreased drastically, and the action potential was unable to generate. These results suggest that the magnetic field simulation can affect the distribution frequency and amplitude of action potential of neuron via sodium channel mediation.

  6. Temporary hearing loss influences post-stimulus time histogram and single neuron action potential estimates from human compound action potentials

    PubMed Central

    Lichtenhan, Jeffery T.; Chertoff, Mark E.

    2008-01-01

    An analytic compound action potential (CAP) obtained by convolving functional representations of the post-stimulus time histogram summed across auditory nerve neurons [P(t)] and a single neuron action potential [U(t)] was fit to human CAPs. The analytic CAP fit to pre- and postnoise-induced temporary hearing threshold shift (TTS) estimated in vivoP(t) and U(t) and the number of neurons contributing to the CAPs (N). The width of P(t) decreased with increasing signal level and was wider at the lowest signal level following noise exposure. P(t) latency decreased with increasing signal level and was shorter at all signal levels following noise exposure. The damping and oscillatory frequency of U(t) increased with signal level. For subjects with large amounts of TTS, U(t) had greater damping than before noise exposure particularly at low signal levels. Additionally, U(t) oscillation was lower in frequency at all click intensities following noise exposure. N increased with signal level and was smaller after noise exposure at the lowest signal level. Collectively these findings indicate that neurons contributing to the CAP during TTS are fewer in number, shorter in latency, and poorer in synchrony than before noise exposure. Moreover, estimates of single neuron action potentials may decay more rapidly and have a lower oscillatory frequency during TTS. PMID:18397026

  7. Mechanisms and consequences of action potential burst firing in rat neocortical pyramidal neurons

    PubMed Central

    Williams, Stephen R; Stuart, Greg J

    1999-01-01

    Electrophysiological recordings and pharmacological manipulations were used to investigate the mechanisms underlying the generation of action potential burst firing and its postsynaptic consequences in visually identified rat layer 5 pyramidal neurons in vitro.Based upon repetitive firing properties and subthreshold membrane characteristics, layer 5 pyramidal neurons were separated into three classes: regular firing and weak and strong intrinsically burst firing.High frequency (330 ± 10 Hz) action potential burst firing was abolished or greatly weakened by the removal of Ca2+ (n = 5) from, or by the addition of the Ca2+ channel antagonist Ni2+ (250–500 μm; n = 8) to, the perfusion medium.The blockade of apical dendritic sodium channels by the local dendritic application of TTX (100 nm; n = 5) abolished or greatly weakened action potential burst firing, as did the local apical dendritic application of Ni2+ (1 mm; n = 5).Apical dendritic depolarisation resulted in low frequency (157 ± 26 Hz; n = 6) action potential burst firing in regular firing neurons, as classified by somatic current injection. The intensity of action potential burst discharges in intrinsically burst firing neurons was facilitated by dendritic depolarisation (n = 11).Action potential amplitude decreased throughout a burst when recorded somatically, suggesting that later action potentials may fail to propagate axonally. Axonal recordings demonstrated that each action potential in a burst is axonally initiated and that no decrement in action potential amplitude is apparent in the axon > 30 μm from the soma.Paired recordings (n = 16) from synaptically coupled neurons indicated that each action potential in a burst could cause transmitter release. EPSPs or EPSCs evoked by a presynaptic burst of action potentials showed use-dependent synaptic depression.A postsynaptic, TTX-sensitive voltage-dependent amplification process ensured that later EPSPs in a burst were amplified when generated from

  8. Dynamics of Action Potential Initiation in the GABAergic Thalamic Reticular Nucleus In Vivo

    PubMed Central

    Muñoz, Fabián; Fuentealba, Pablo

    2012-01-01

    Understanding the neural mechanisms of action potential generation is critical to establish the way neural circuits generate and coordinate activity. Accordingly, we investigated the dynamics of action potential initiation in the GABAergic thalamic reticular nucleus (TRN) using in vivo intracellular recordings in cats in order to preserve anatomically-intact axo-dendritic distributions and naturally-occurring spatiotemporal patterns of synaptic activity in this structure that regulates the thalamic relay to neocortex. We found a wide operational range of voltage thresholds for action potentials, mostly due to intrinsic voltage-gated conductances and not synaptic activity driven by network oscillations. Varying levels of synchronous synaptic inputs produced fast rates of membrane potential depolarization preceding the action potential onset that were associated with lower thresholds and increased excitability, consistent with TRN neurons performing as coincidence detectors. On the other hand the presence of action potentials preceding any given spike was associated with more depolarized thresholds. The phase-plane trajectory of the action potential showed somato-dendritic propagation, but no obvious axon initial segment component, prominent in other neuronal classes and allegedly responsible for the high onset speed. Overall, our results suggest that TRN neurons could flexibly integrate synaptic inputs to discharge action potentials over wide voltage ranges, and perform as coincidence detectors and temporal integrators, supported by a dynamic action potential threshold. PMID:22279567

  9. Dynamics of action potential initiation in the GABAergic thalamic reticular nucleus in vivo.

    PubMed

    Muñoz, Fabián; Fuentealba, Pablo

    2012-01-01

    Understanding the neural mechanisms of action potential generation is critical to establish the way neural circuits generate and coordinate activity. Accordingly, we investigated the dynamics of action potential initiation in the GABAergic thalamic reticular nucleus (TRN) using in vivo intracellular recordings in cats in order to preserve anatomically-intact axo-dendritic distributions and naturally-occurring spatiotemporal patterns of synaptic activity in this structure that regulates the thalamic relay to neocortex. We found a wide operational range of voltage thresholds for action potentials, mostly due to intrinsic voltage-gated conductances and not synaptic activity driven by network oscillations. Varying levels of synchronous synaptic inputs produced fast rates of membrane potential depolarization preceding the action potential onset that were associated with lower thresholds and increased excitability, consistent with TRN neurons performing as coincidence detectors. On the other hand the presence of action potentials preceding any given spike was associated with more depolarized thresholds. The phase-plane trajectory of the action potential showed somato-dendritic propagation, but no obvious axon initial segment component, prominent in other neuronal classes and allegedly responsible for the high onset speed. Overall, our results suggest that TRN neurons could flexibly integrate synaptic inputs to discharge action potentials over wide voltage ranges, and perform as coincidence detectors and temporal integrators, supported by a dynamic action potential threshold.

  10. All optical experimental design for neuron excitation, inhibition, and action potential detection

    NASA Astrophysics Data System (ADS)

    Walsh, Alex J.; Tolstykh, Gleb; Martens, Stacey; Sedelnikova, Anna; Ibey, Bennett L.; Beier, Hope T.

    2016-03-01

    Recently, infrared light has been shown to both stimulate and inhibit excitatory cells. However, studies of infrared light for excitatory cell inhibition have been constrained by the use of invasive and cumbersome electrodes for cell excitation and action potential recording. Here, we present an all optical experimental design for neuronal excitation, inhibition, and action potential detection. Primary rat neurons were transfected with plasmids containing the light sensitive ion channel CheRiff. CheRiff has a peak excitation around 450 nm, allowing excitation of transfected neurons with pulsed blue light. Additionally, primary neurons were transfected with QuasAr2, a fast and sensitive fluorescent voltage indicator. QuasAr2 is excited with yellow or red light and therefore does not spectrally overlap CheRiff, enabling imaging and action potential activation, simultaneously. Using an optic fiber, neurons were exposed to blue light sequentially to generate controlled action potentials. A second optic fiber delivered a single pulse of 1869nm light to the neuron causing inhibition of the evoked action potentials (by the blue light). When used in concert, these optical techniques enable electrode free neuron excitation, inhibition, and action potential recording, allowing research into neuronal behaviors with high spatial fidelity.

  11. Cortical Action Potential Backpropagation Explains Spike Threshold Variability and Rapid-Onset Kinetics

    PubMed Central

    Yu, Yuguo; Shu, Yousheng; McCormick, David A.

    2008-01-01

    Neocortical action potential responses in vivo are characterized by considerable threshold variability, and thus timing and rate variability, even under seemingly identical conditions. This finding suggests that cortical ensembles are required for accurate sensorimotor integration and processing. Intracellularly, trial-to-trial variability results not only from variation in synaptic activities, but also in the transformation of these into patterns of action potentials. Through simultaneous axonal and somatic recordings and computational simulations, we demonstrate that the initiation of action potentials in the axon initial segment followed by backpropagation of these spikes throughout the neuron results in a distortion of the relationship between the timing of synaptic and action potential events. In addition, this backpropagation also results in an unusually high rate of rise of membrane potential at the foot of the action potential. The distortion of the relationship between the amplitude time course of synaptic inputs and action potential output caused by spike back-propagation results in the appearance of high spike threshold variability at the level of the soma. At the point of spike initiation, the axon initial segment, threshold variability is considerably less. Our results indicate that spike generation in cortical neurons is largely as expected by Hodgkin—Huxley theory and is more precise than previously thought. PMID:18632930

  12. Action potential properties are gravity dependent

    NASA Astrophysics Data System (ADS)

    Meissner, Klaus; Hanke, Wolfgang

    2005-06-01

    The functional properties of neuronal tissue critically depend on cellular composition and intercellular comunication. A basic principle of such communication found in various types of neurons is the generation of action potentials (APs). These APs depend on the presence of voltage gated ion channels and propagate along cellular processes (e.g. axons) towards target neurons or other cells. It has already been shown that the properties of ion channels depend on gravity. To discover whether the properties of APs also depend on gravity, we examined the propagation of APs in earthworms (invertebrates) and isolated nerve fibres (i.e. bundles of axons) from earthworms under conditions of micro- and macro-gravity. In a second set of experiments we could verify our results on rat axons (vertebrates). Our experiments carried out during two parabolic flight campaigns revealed that microgravity slows AP propagation velocity and macrogravity accelerates the transmission of action potentials. The relevance for live-science related questions is considerable, taking into account that altered gravity conditions might affect AP velocity in man during space flight missions.

  13. Characteristics of action potentials and their underlying outward currents in rat taste receptor cells.

    PubMed

    Chen, Y; Sun, X D; Herness, S

    1996-02-01

    1. Taste receptor cells produce action potentials as a result of transduction mechanisms that occur when these cells are stimulated with tastants. These action potentials are thought to be key signaling events in relaying information to the central nervous system. We explored the ionic basis of action potentials from dissociated posterior rat taste cells using the patch-clamp recording technique in both voltage-clamp and current-clamp modes. 2. Action potentials were evoked by intracellular injection of depolarizing current pulses from a holding potential of -80 mV. The threshold potential for firing of action potentials was approximately -35 mV; the input resistance of these cells averaged 6.9 G omega. With long depolarizing pulses, two or three action potentials could be elicited with successive attenuation of the spike height. Afterhyperpolarizations were observed often. 3. Both sodium and calcium currents contribute to depolarizing phases of the action potential. Action potentials were blocked completely in the presence of the sodium channel blocker tetrodotoxin. Calcium contributions could be visualized as prolonged calcium plateaus when repolarizing potassium currents were blocked and barium was used as a charge carrier. 4. Outward currents were composed of sustained delayed rectifier current, transient potassium current, and calcium-activated potassium current. Transient and sustained potassium currents activated close to -30 mV and increased monotonically with further depolarization. Up to half the outward current inactivated with decay constants on the order of seconds. Sustained and transient currents displayed steep voltage dependence in conductance and inactivation curves. Half inactivation occurred at -20 +/- 3.1 mV (mean +/- SE) with a decrease of 11.2 +/- 0.5 mV per e-fold. Half maximal conductance occurred at 3.6 +/- 1.8 mV and increased 12.2 +/- 0.6 mV per e-fold. Calcium-activated potassium current was evidenced by application of apamin and the

  14. Effect of an educational game on university students' learning about action potentials.

    PubMed

    Luchi, Kelly Cristina Gaviao; Montrezor, Luís Henrique; Marcondes, Fernanda K

    2017-06-01

    The aim of this study was to evaluate the effect of an educational game that is used for teaching the mechanisms of the action potentials in cell membranes. The game was composed of pieces representing the intracellular and extracellular environments, ions, ion channels, and the Na + -K + -ATPase pump. During the game activity, the students arranged the pieces to demonstrate how the ions move through the membrane in a resting state and during an action potential, linking the ion movement with a graph of the action potential. To test the effect of the game activity on student understanding, first-year dental students were given the game to play at different times in a series of classes teaching resting membrane potential and action potentials. In all experiments, students who played the game performed better in assessments. According to 98% of the students, the game supported the learning process. The data confirm the students' perception, indicating that the educational game improved their understanding about action potentials. Copyright © 2017 the American Physiological Society.

  15. Inducing repetitive action potential firing in neurons via synthesized photoresponsive nanoscale cellular prostheses.

    PubMed

    Lu, Siyuan; Madhukar, Anupam

    2013-02-01

    Recently we reported an analysis that examined the potential of synthesized photovoltaic functional abiotic nanosystems (PVFANs) to modulate membrane potential and activate action potential firing in neurons. Here we extend the analysis to delineate the requirements on the electronic energy levels and the attendant photophysical properties of the PVFANs to induce repetitive action potential under continuous light, a capability essential for the proposed potential application of PVFANs as retinal cellular prostheses to compensate for loss of photoreceptors. We find that repetitive action potential firing demands two basic characteristics in the electronic response of the PVFANs: an exponential dependence of the PVFAN excited state decay rate on the membrane potential and a three-state system such that, following photon absorption, the electron decay from the excited state to the ground state is via intermediate state(s) whose lifetime is comparable to the refractory time following an action potential. In this study, the potential of synthetic photovoltaic functional abiotic nanosystems (PVFANs) is examined under continuous light to modulate membrane potential and activate action potential firing in neurons with the proposed potential application of PVFANs as retinal cellular prostheses. Copyright © 2013 Elsevier Inc. All rights reserved.

  16. A phantom axon setup for validating models of action potential recordings.

    PubMed

    Rossel, Olivier; Soulier, Fabien; Bernard, Serge; Guiraud, David; Cathébras, Guy

    2016-08-01

    Electrode designs and strategies for electroneurogram recordings are often tested first by computer simulations and then by animal models, but they are rarely implanted for long-term evaluation in humans. The models show that the amplitude of the potential at the surface of an axon is higher in front of the nodes of Ranvier than at the internodes; however, this has not been investigated through in vivo measurements. An original experimental method is presented to emulate a single fiber action potential in an infinite conductive volume, allowing the potential of an axon to be recorded at both the nodes of Ranvier and the internodes, for a wide range of electrode-to-fiber radial distances. The paper particularly investigates the differences in the action potential amplitude along the longitudinal axis of an axon. At a short radial distance, the action potential amplitude measured in front of a node of Ranvier is two times larger than in the middle of two nodes. Moreover, farther from the phantom axon, the measured action potential amplitude is almost constant along the longitudinal axis. The results of this new method confirm the computer simulations, with a correlation of 97.6 %.

  17. Minocycline inhibits D-amphetamine-elicited action potential bursts in a central snail neuron.

    PubMed

    Chen, Y-H; Lin, P-L; Wong, R-W; Wu, Y-T; Hsu, H-Y; Tsai, M-C; Lin, M-J; Hsu, Y-C; Lin, C-H

    2012-10-25

    Minocycline is a second-generation tetracycline that has been reported to have powerful neuroprotective properties. In our previous studies, we found that d-amphetamine (AMPH) elicited action potential bursts in an identifiable RP4 neuron of the African snail, Achatina fulica Ferussac. This study sought to determine the effects of minocycline on the AMPH-elicited action potential pattern changes in the central snail neuron, using the two-electrode voltage clamping method. Extracellular application of AMPH at 300 μM elicited action potential bursts in the RP4 neuron. Minocycline dose-dependently (300-900 μM) inhibited the action potential bursts elicited by AMPH. The inhibitory effects of minocycline on AMPH-elicited action potential bursts were restored by forskolin (50 μM), an adenylate cyclase activator, and by dibutyryl cAMP (N(6),2'-O-Dibutyryladenosine 3',5'-cyclic monophosphate; 1mM), a membrane-permeable cAMP analog. Co-administration of forskolin (50 μM) plus tetraethylammonium chloride (TEA; 5mM) or co-administration of TEA (5mM) plus dibutyryl cAMP (1mM) also elicited action potential bursts, which were prevented and inhibited by minocycline. In addition, minocycline prevented and inhibited forskolin (100 μM)-elicited action potential bursts. Notably, TEA (50mM)-elicited action potential bursts in the RP4 neuron were not affected by minocycline. Minocycline did not affect steady-state outward currents of the RP4 neuron. However, minocycline did decrease the AMPH-elicited steady-state current changes. Similarly, minocycline decreased the effects of forskolin-elicited steady-state current changes. Pretreatment with H89 (N-[2-(p-Bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide dihydrochloride; 10 μM), a protein kinase A inhibitor, inhibited AMPH-elicited action potential bursts and decreased AMPH-elicited steady-state current changes. These results suggest that the cAMP-protein kinase A signaling pathway and the steady-state current are involved in

  18. Na and Ca components of action potentials in amphioxus muscle cells

    PubMed Central

    Hagiwara, S.; Kidokoro, Y.

    1971-01-01

    1. The ionic mechanism of the action potential produced in lamella-like muscle cells of amphioxus, Branchiostoma californiense, was investigated with intracellular recording and polarization techniques. 2. The resting potential and action potential overshoot in normal saline are -53±5 mV (S.D.) and +29±10 mV (S.D.) respectively. 3. The action potential is eliminated by tetrodotoxin (3 μM) and by replacing NaCl in the saline with Tris-chloride but maintained by replacing Na with Li. 4. After elimination of the normal action potential by tetrodotoxin or replacing Na with Tris, the addition of procaine (7·3 mM) to the external saline makes the membrane capable of producing a regenerative potential change. 5. The peak potential of the regenerative response depends on external Ca concentration in a manner predicted by the Nernst equation with Ca concentrations close to normal. 6. The Ca dependent response is reversibly suppressed by Co or La ions. 7. Similar regenerative responses are obtained when Ca is substituted with Sr or Ba. 8. It is concluded that two independent mechanisms of ionic permeability increase occur in the membrane of amphioxus muscle cell, one to Na and the other to Ca. PMID:5158595

  19. Generation of action potentials in a mathematical model of corticotrophs.

    PubMed Central

    LeBeau, A P; Robson, A B; McKinnon, A E; Donald, R A; Sneyd, J

    1997-01-01

    Corticotropin-releasing hormone (CRH) is an important regulator of adrenocorticotropin (ACTH) secretion from pituitary corticotroph cells. The intracellular signaling system that underlies this process involves modulation of voltage-sensitive Ca2+ channel activity, which leads to the generation of Ca2+ action potentials and influx of Ca2+. However, the mechanisms by which Ca2+ channel activity is modulated in corticotrophs are not currently known. We investigated this process in a Hodgkin-Huxley-type mathematical model of corticotroph plasma membrane electrical responses. We found that an increase in the L-type Ca2+ current was sufficient to generate action potentials from a previously resting state of the model. The increase in the L-type current could be elicited by either a shift in the voltage dependence of the current toward more negative potentials, or by an increase in the conductance of the current. Although either of these mechanisms is potentially responsible for the generation of action potentials, previous experimental evidence favors the former mechanism, with the magnitude of the shift required being consistent with the experimental findings. The model also shows that the T-type Ca2+ current plays a role in setting the excitability of the plasma membrane, but does not appear to contribute in a dynamic manner to action potential generation. Inhibition of a K+ conductance that is active at rest also affects the excitability of the plasma membrane. PMID:9284294

  20. Sodium and potassium conductance changes during a membrane action potential

    PubMed Central

    Bezanilla, Francisco; Rojas, Eduardo; Taylor, Robert E.

    1970-01-01

    1. A method for turning a membrane potential control system on and off in less than 10 μsec is described. This method was used to record membrane currents in perfused giant axons from Dosidicus gigas and Loligo forbesi after turning on the voltage clamp system at various times during the course of a membrane action potential. 2. The membrane current measured just after the capacity charging transient was found to have an almost linear relation to the controlled membrane potential. 3. The total membrane conductance taken from these current—voltage curves was found to have a time course during the action potential similar to that found by Cole & Curtis (1939). 4. The instantaneous current voltage curves were linear enough to make it possible to obtain a good estimate of the individual sodium and potassium channel conductances, either algebraically or by clamping to the sodium, or potassium, reversal potentials. Good general agreement was obtained with the predictions of the Hodgkin—Huxley equations. 5. We consider these results to constitute the first direct experimental demonstration of the conductance changes to sodium and potassium during the course of an action potential. PMID:5505231

  1. Sodium and potassium conductance changes during a membrane action potential.

    PubMed

    Bezanilla, F; Rojas, E; Taylor, R E

    1970-12-01

    1. A method for turning a membrane potential control system on and off in less than 10 musec is described. This method was used to record membrane currents in perfused giant axons from Dosidicus gigas and Loligo forbesi after turning on the voltage clamp system at various times during the course of a membrane action potential.2. The membrane current measured just after the capacity charging transient was found to have an almost linear relation to the controlled membrane potential.3. The total membrane conductance taken from these current-voltage curves was found to have a time course during the action potential similar to that found by Cole & Curtis (1939).4. The instantaneous current voltage curves were linear enough to make it possible to obtain a good estimate of the individual sodium and potassium channel conductances, either algebraically or by clamping to the sodium, or potassium, reversal potentials. Good general agreement was obtained with the predictions of the Hodgkin-Huxley equations.5. We consider these results to constitute the first direct experimental demonstration of the conductance changes to sodium and potassium during the course of an action potential.

  2. On cuff imbalance and tripolar ENG amplifier configurations.

    PubMed

    Triantis, Iasonas F; Demosthenous, Andreas; Donaldson, Nick

    2005-02-01

    Electroneurogram (ENG) recording techniques benefit from the use of tripolar cuffs because they assist in reducing interference from sources outside the cuff. However, in practice the performance of ENG amplifier configurations, such as the quasi-tripole and the true-tripole, has been widely reported to be degraded due to the departure of the tripolar cuff from ideal behavior. This paper establishes the presence of cuff imbalance and investigates its relationship to cuff asymmetry, cuff end-effects and interference source proximity. The paper also presents a comparison of the aforementioned amplifier configurations with a new alternative, termed the adaptive-tripole, developed to automatically compensate for cuff imbalance. The output signal-to-interference ratio of the three amplifier configurations were compared in vivo for two interference signals (stimulus artifact and M-wave) superimposed on compound action potentials. The experiments showed (for the first time) that the two interference signals result in different cuff imbalance values. Nevertheless, even with two distinct cuff imbalances present, the adaptive-tripole performed better than the other two systems in 61.9% of the trials.

  3. Mechanisms of action of ligands of potential-dependent sodium channels.

    PubMed

    Tikhonov, D B

    2008-06-01

    Potential-dependent sodium channels play a leading role in generating action potentials in excitable cells. Sodium channels are the site of action of a variety of modulator ligands. Despite numerous studies, the mechanisms of action of many modulators remain incompletely understood. The main reason that many important questions cannot be resolved is that there is a lack of precise data on the structures of the channels themselves. Structurally, potential-dependent sodium channels are members of the P-loop channel superfamily, which also include potassium and calcium channels and glutamate receptor channels. Crystallization of a series of potassium channels showed that it was possible to analyze the structures of different members of the superfamily using the "homologous modeling" method. The present study addresses model investigations of the actions of ligands of sodium channels, including tetrodotoxin and batrachotoxin, as well as local anesthetics. Comparison of experimental data on sodium channel ligands with x-ray analysis data allowed us to reach a new level of understanding of the mechanisms of channel modulation and to propose a series of experimentally verifiable hypotheses.

  4. [Patterns of action potential firing in cortical neurons of neonatal mice and their electrophysiological property].

    PubMed

    Furong, Liu; Shengtian, L I

    2016-05-25

    To investigate patterns of action potential firing in cortical heurons of neonatal mice and their electrophysiological properties. The passive and active membrane properties of cortical neurons from 3-d neonatal mice were observed by whole-cell patch clamp with different voltage and current mode. Three patterns of action potential firing were identified in response to depolarized current injection. The effects of action potential firing patterns on voltage-dependent inward and outward current were found. Neurons with three different firing patterns had different thresholds of depolarized current. In the morphology analysis of action potential, the three type neurons were different in rise time, duration, amplitude and threshold of the first action potential evoked by 80 pA current injection. The passive properties were similar in three patterns of action potential firing. These results indicate that newborn cortical neurons exhibit different patterns of action potential firing with different action potential parameters such as shape and threshold.

  5. Prolonged action potential duration in cardiac ablation of PDK1 mice.

    PubMed

    Han, Zhonglin; Jiang, Yu; Yang, Zhongzhou; Cao, Kejiang; Wang, Dao W

    2015-01-01

    The involvement of the AGC protein kinase family in regulating arrhythmia has drawn considerable attention, but the underlying mechanisms are still not clear. The aim of this study is to explore the role of 3-phosphoinositide-dependent protein kinase-1 (PDK1), one of upstream protein kinases of the AGC protein kinase family, in the pathogenesis of dysregulated electrophysiological basis. PDK1(F/F) αMHC-Cre mice and PDK1(F/F) mice were divided into experiment group and control group. Using patch clamping technology, we explored action potential duration in both groups, and investigated the functions of transient outward potassium channel and L-type Ca(2+) channel to explain the abnormal action potential duration. Significant prolongation action potential duration was found in mice with PDK1 deletion. Further, the peak current of transient outward potassium current and L-type Ca(2+) current were decreased by 84% and 49% respectively. In addition, dysregulation of channel kinetics lead to action potential duration prolongation further. In conclusion, we have demonstrated that PDK1 participates in action potential prolongation in cardiac ablation of PDK1 mice. This effect is likely to be mediated largely through downregulation of transient outward potassium current. These findings indicate the modulation of the PDK1 pathway could provide a new mechanism for abnormal electrophysiological basis.

  6. Stimulus waveform determines the characteristics of sensory nerve action potentials.

    PubMed

    Pereira, Pedro; Leote, João; Cabib, Christopher; Casanova-Molla, Jordi; Valls-Sole, Josep

    2016-03-01

    In routine nerve conduction studies supramaximal electrical stimuli generate sensory nerve action potentials by depolarization of nerve fibers under the cathode. However, stimuli of submaximal intensity may give rise to action potentials generated under the anode. We tested if this phenomenon depends on the characteristics of stimulus ending. We added a circuit to our stimulation device that allowed us to modify the end of the stimulus by increasing the time constant of the decay phase. Increasing the fall time caused a reduction of anode action potential (anAP) amplitude, and eventually abolished it, in all tested subjects. We subsequently examined the stimulus waveform in a series of available electromyographs stimulators and found that the anAP could only be obtained with stimulators that issued stimuli ending sharply. Our results prove that the anAP is generated at stimulus end, and depends on the sharpness of current shut down. Electromyographs produce stimuli of varying characteristics, which limits the reproducibility of anAP results by interested researchers. The study of anodal action potentials might be a useful tool to have a quick appraisal of distal human sensory nerve excitability. Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  7. Design issues for optimum solar cell configuration

    NASA Astrophysics Data System (ADS)

    Kumar, Atul; Thakur, Ajay D.

    2018-05-01

    A computer based simulation of solar cell structure is performed to study the optimization of pn junction configuration for photovoltaic action. The fundamental aspects of photovoltaic action viz, absorption, separation collection, and their dependence on material properties and deatails of device structures is discussed. Using SCAPS 1D we have simulated the ideal pn junction and shown the effect of band offset and carrier densities on solar cell performance. The optimum configuration can be achieved by optimizing transport of carriers in pn junction under effect of field dependent recombination (tunneling) and density dependent recombination (SRH, Auger) mechanisms.

  8. Action prediction based on anticipatory brain potentials during simulated driving.

    PubMed

    Khaliliardali, Zahra; Chavarriaga, Ricardo; Gheorghe, Lucian Andrei; Millán, José del R

    2015-12-01

    The ability of an automobile to infer the driver's upcoming actions directly from neural signals could enrich the interaction of the car with its driver. Intelligent vehicles fitted with an on-board brain-computer interface able to decode the driver's intentions can use this information to improve the driving experience. In this study we investigate the neural signatures of anticipation of specific actions, namely braking and accelerating. We investigated anticipatory slow cortical potentials in electroencephalogram recorded from 18 healthy participants in a driving simulator using a variant of the contingent negative variation (CNV) paradigm with Go and No-go conditions: count-down numbers followed by 'Start'/'Stop' cue. We report decoding performance before the action onset using a quadratic discriminant analysis classifier based on temporal features. (i) Despite the visual and driving related cognitive distractions, we show the presence of anticipatory event related potentials locked to the stimuli onset similar to the widely reported CNV signal (with an average peak value of -8 μV at electrode Cz). (ii) We demonstrate the discrimination between cases requiring to perform an action upon imperative subsequent stimulus (Go condition, e.g. a 'Red' traffic light) versus events that do not require such action (No-go condition; e.g. a 'Yellow' light); with an average single trial classification performance of 0.83 ± 0.13 for braking and 0.79 ± 0.12 for accelerating (area under the curve). (iii) We show that the centro-medial anticipatory potentials are observed as early as 320 ± 200 ms before the action with a detection rate of 0.77 ± 0.12 in offline analysis. We show for the first time the feasibility of predicting the driver's intention through decoding anticipatory related potentials during simulated car driving with high recognition rates.

  9. Action prediction based on anticipatory brain potentials during simulated driving

    NASA Astrophysics Data System (ADS)

    Khaliliardali, Zahra; Chavarriaga, Ricardo; Gheorghe, Lucian Andrei; Millán, José del R.

    2015-12-01

    Objective. The ability of an automobile to infer the driver’s upcoming actions directly from neural signals could enrich the interaction of the car with its driver. Intelligent vehicles fitted with an on-board brain-computer interface able to decode the driver’s intentions can use this information to improve the driving experience. In this study we investigate the neural signatures of anticipation of specific actions, namely braking and accelerating. Approach. We investigated anticipatory slow cortical potentials in electroencephalogram recorded from 18 healthy participants in a driving simulator using a variant of the contingent negative variation (CNV) paradigm with Go and No-go conditions: count-down numbers followed by ‘Start’/‘Stop’ cue. We report decoding performance before the action onset using a quadratic discriminant analysis classifier based on temporal features. Main results. (i) Despite the visual and driving related cognitive distractions, we show the presence of anticipatory event related potentials locked to the stimuli onset similar to the widely reported CNV signal (with an average peak value of -8 μV at electrode Cz). (ii) We demonstrate the discrimination between cases requiring to perform an action upon imperative subsequent stimulus (Go condition, e.g. a ‘Red’ traffic light) versus events that do not require such action (No-go condition; e.g. a ‘Yellow’ light); with an average single trial classification performance of 0.83 ± 0.13 for braking and 0.79 ± 0.12 for accelerating (area under the curve). (iii) We show that the centro-medial anticipatory potentials are observed as early as 320 ± 200 ms before the action with a detection rate of 0.77 ± 0.12 in offline analysis. Significance. We show for the first time the feasibility of predicting the driver’s intention through decoding anticipatory related potentials during simulated car driving with high recognition rates.

  10. TRH regulates action potential shape in cerebral cortex pyramidal neurons.

    PubMed

    Rodríguez-Molina, Víctor; Patiño, Javier; Vargas, Yamili; Sánchez-Jaramillo, Edith; Joseph-Bravo, Patricia; Charli, Jean-Louis

    2014-07-07

    Thyrotropin releasing hormone (TRH) is a neuropeptide with a wide neural distribution and a variety of functions. It modulates neuronal electrophysiological properties, including resting membrane potential, as well as excitatory postsynaptic potential and spike frequencies. We explored, with whole-cell patch clamp, TRH effect on action potential shape in pyramidal neurons of the sensorimotor cortex. TRH reduced spike and after hyperpolarization amplitudes, and increased spike half-width. The effect varied with dose, time and cortical layer. In layer V, 0.5µM of TRH induced a small increase in spike half-width, while 1 and 5µM induced a strong but transient change in spike half-width, and amplitude; after hyperpolarization amplitude was modified at 5µM of TRH. Cortical layers III and VI neurons responded intensely to 0.5µM TRH; layer II neurons response was small. The effect of 1µM TRH on action potential shape in layer V neurons was blocked by G-protein inhibition. Inhibition of the activity of the TRH-degrading enzyme pyroglutamyl peptidase II (PPII) reproduced the effect of TRH, with enhanced spike half-width. Many cortical PPII mRNA+ cells were VGLUT1 mRNA+, and some GAD mRNA+. These data show that TRH regulates action potential shape in pyramidal cortical neurons, and are consistent with the hypothesis that PPII controls its action in this region. Copyright © 2014 Elsevier B.V. All rights reserved.

  11. Multireference configuration interaction calculations of the first six ionization potentials of the uranium atom

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Bross, David H.; Parmar, Payal; Peterson, Kirk A.

    The first 6 ionization potentials (IPs) of the uranium atom have been calculated using multireference configuration interaction (MRCI+Q) with extrapolations to the complete basis set (CBS) limit using new all-electron correlation consistent basis sets. The latter were carried out with the third-order Douglas-Kroll-Hess Hamiltonian. Correlation down through the 5s5p5d electrons have been taken into account, as well as contributions to the IPs due to the Lamb shift. Spin-orbit coupling contributions calculated at the 4-component Kramers restricted configuration interaction level, as well as the Gaunt term computed at the Dirac-Hartree-Fock level, were added to the best scalar relativistic results. As amore » result, the final ionization potentials are expected to be accurate to at least 5 kcal/mol (0.2 eV), and thus more reliable than the current experimental values of IP 3 through IP 6.« less

  12. Multireference configuration interaction calculations of the first six ionization potentials of the uranium atom

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Bross, David H.; Parmar, Payal; Peterson, Kirk A., E-mail: kipeters@wsu.edu

    The first 6 ionization potentials (IPs) of the uranium atom have been calculated using multireference configuration interaction (MRCI+Q) with extrapolations to the complete basis set limit using new all-electron correlation consistent basis sets. The latter was carried out with the third-order Douglas-Kroll-Hess Hamiltonian. Correlation down through the 5s5p5d electrons has been taken into account, as well as contributions to the IPs due to the Lamb shift. Spin-orbit coupling contributions calculated at the 4-component Kramers restricted configuration interaction level, as well as the Gaunt term computed at the Dirac-Hartree-Fock level, were added to the best scalar relativistic results. The final ionizationmore » potentials are expected to be accurate to at least 5 kcal/mol (0.2 eV) and thus more reliable than the current experimental values of IP{sub 3} through IP{sub 6}.« less

  13. Voltage-gated sodium channel expression and action potential generation in differentiated NG108-15 cells.

    PubMed

    Liu, Jinxu; Tu, Huiyin; Zhang, Dongze; Zheng, Hong; Li, Yu-Long

    2012-10-25

    The generation of action potential is required for stimulus-evoked neurotransmitter release in most neurons. Although various voltage-gated ion channels are involved in action potential production, the initiation of the action potential is mainly mediated by voltage-gated Na+ channels. In the present study, differentiation-induced changes of mRNA and protein expression of Na+ channels, Na+ currents, and cell membrane excitability were investigated in NG108-15 cells. Whole-cell patch-clamp results showed that differentiation (9 days) didn't change cell membrane excitability, compared to undifferentiated state. But differentiation (21 days) induced the action potential generation in 45.5% of NG108-15 cells (25/55 cells). In 9-day-differentiated cells, Na+ currents were mildly increased, which was also found in 21-day differentiated cells without action potential. In 21-day differentiated cells with action potential, Na+ currents were significantly enhanced. Western blot data showed that the expression of Na+ channels was increased with differentiated-time dependent manner. Single-cell real-time PCR data demonstrated that the expression of Na+ channel mRNA was increased by 21 days of differentiation in NG108-15 cells. More importantly, the mRNA level of Na+ channels in cells with action potential was higher than that in cells without action potential. Differentiation induces expression of voltage-gated Na+ channels and action potential generation in NG108-15 cells. A high level of the Na+ channel density is required for differentiation-triggered action potential generation.

  14. Membrane, action, and oscillatory potentials in simulated protocells

    NASA Technical Reports Server (NTRS)

    Syren, R. M.; Fox, S. W.; Przybylski, A. T.; Stratten, W. P.

    1982-01-01

    Electrical membrane potentials, oscillations, and action potentials are observed in proteinoid microspheres impaled with (3 M KCl) microelectrodes. Although effects are of greater magnitude when the vesicles contain glycerol and natural or synthetic lecithin, the results in the purely synthetic thermal protein structures are substantial, attaining 20 mV amplitude in some cases. The results add the property of electrical potential to the other known properties of proteinoid microspheres, in their role as models for protocells.

  15. Computer Simulation of the Neuronal Action Potential.

    ERIC Educational Resources Information Center

    Solomon, Paul R.; And Others

    1988-01-01

    A series of computer simulations of the neuronal resting and action potentials are described. Discusses the use of simulations to overcome the difficulties of traditional instruction, such as blackboard illustration, which can only illustrate these events at one point in time. Describes systems requirements necessary to run the simulations.…

  16. Introducing the Action Potential to Psychology Students

    ERIC Educational Resources Information Center

    Simon-Dack, Stephanie L.

    2014-01-01

    For this simple active learning technique for teaching, students are assigned "roles" and act out the process of the action potential (AP), including the firing threshold, ion-specific channels for ions to enter and leave the cell, diffusion, and the refractory period. Pre-post test results indicated that students demonstrated increased…

  17. Aspects of manual wheelchair configuration affecting mobility: a review.

    PubMed

    Medola, Fausto Orsi; Elui, Valeria Meirelles Carril; Santana, Carla da Silva; Fortulan, Carlos Alberto

    2014-02-01

    Many aspects relating to equipment configuration affect users' actions in a manual wheelchair, determining the overall mobility performance. Since the equipment components and configuration determine both stability and mobility efficiency, configuring the wheelchair with the most appropriate set-up for individual users' needs is a difficult task. Several studies have shown the importance of seat/backrest assembly and the relative position of the rear wheels to the user in terms of the kinetics and kinematics of manual propulsion. More recently, new studies have brought to light evidence on the inertial properties of different wheelchair configurations. Further new studies have highlighted the handrim as a key component of wheelchair assembly, since it is the interface through which the user drives the chair. In light of the new evidence on wheelchair mechanics and propulsion kinetics and kinematics, this article presents a review of the most important aspects of wheelchair configuration that affect the users' actions and mobility.

  18. Aspects of Manual Wheelchair Configuration Affecting Mobility: A Review

    PubMed Central

    Medola, Fausto Orsi; Elui, Valeria Meirelles Carril; Santana, Carla da Silva; Fortulan, Carlos Alberto

    2014-01-01

    Many aspects relating to equipment configuration affect users’ actions in a manual wheelchair, determining the overall mobility performance. Since the equipment components and configuration determine both stability and mobility efficiency, configuring the wheelchair with the most appropriate set-up for individual users’ needs is a difficult task. Several studies have shown the importance of seat/backrest assembly and the relative position of the rear wheels to the user in terms of the kinetics and kinematics of manual propulsion. More recently, new studies have brought to light evidence on the inertial properties of different wheelchair configurations. Further new studies have highlighted the handrim as a key component of wheelchair assembly, since it is the interface through which the user drives the chair. In light of the new evidence on wheelchair mechanics and propulsion kinetics and kinematics, this article presents a review of the most important aspects of wheelchair configuration that affect the users’ actions and mobility. PMID:24648656

  19. Alteration of neural action potential patterns by axonal stimulation: the importance of stimulus location

    NASA Astrophysics Data System (ADS)

    Crago, Patrick E.; Makowski, Nathaniel S.

    2014-10-01

    Objective. Stimulation of peripheral nerves is often superimposed on ongoing motor and sensory activity in the same axons, without a quantitative model of the net action potential train at the axon endpoint. Approach. We develop a model of action potential patterns elicited by superimposing constant frequency axonal stimulation on the action potentials arriving from a physiologically activated neural source. The model includes interactions due to collision block, resetting of the neural impulse generator, and the refractory period of the axon at the point of stimulation. Main results. Both the mean endpoint firing rate and the probability distribution of the action potential firing periods depend strongly on the relative firing rates of the two sources and the intersite conduction time between them. When the stimulus rate exceeds the neural rate, neural action potentials do not reach the endpoint and the rate of endpoint action potentials is the same as the stimulus rate, regardless of the intersite conduction time. However, when the stimulus rate is less than the neural rate, and the intersite conduction time is short, the two rates partially sum. Increases in stimulus rate produce non-monotonic increases in endpoint rate and continuously increasing block of neurally generated action potentials. Rate summation is reduced and more neural action potentials are blocked as the intersite conduction time increases. At long intersite conduction times, the endpoint rate simplifies to being the maximum of either the neural or the stimulus rate. Significance. This study highlights the potential of increasing the endpoint action potential rate and preserving neural information transmission by low rate stimulation with short intersite conduction times. Intersite conduction times can be decreased with proximal stimulation sites for muscles and distal stimulation sites for sensory endings. The model provides a basis for optimizing experiments and designing neuroprosthetic

  20. Alteration of neural action potential patterns by axonal stimulation: the importance of stimulus location.

    PubMed

    Crago, Patrick E; Makowski, Nathaniel S

    2014-10-01

    Stimulation of peripheral nerves is often superimposed on ongoing motor and sensory activity in the same axons, without a quantitative model of the net action potential train at the axon endpoint. We develop a model of action potential patterns elicited by superimposing constant frequency axonal stimulation on the action potentials arriving from a physiologically activated neural source. The model includes interactions due to collision block, resetting of the neural impulse generator, and the refractory period of the axon at the point of stimulation. Both the mean endpoint firing rate and the probability distribution of the action potential firing periods depend strongly on the relative firing rates of the two sources and the intersite conduction time between them. When the stimulus rate exceeds the neural rate, neural action potentials do not reach the endpoint and the rate of endpoint action potentials is the same as the stimulus rate, regardless of the intersite conduction time. However, when the stimulus rate is less than the neural rate, and the intersite conduction time is short, the two rates partially sum. Increases in stimulus rate produce non-monotonic increases in endpoint rate and continuously increasing block of neurally generated action potentials. Rate summation is reduced and more neural action potentials are blocked as the intersite conduction time increases. At long intersite conduction times, the endpoint rate simplifies to being the maximum of either the neural or the stimulus rate. This study highlights the potential of increasing the endpoint action potential rate and preserving neural information transmission by low rate stimulation with short intersite conduction times. Intersite conduction times can be decreased with proximal stimulation sites for muscles and distal stimulation sites for sensory endings. The model provides a basis for optimizing experiments and designing neuroprosthetic interventions involving motor or sensory stimulation.

  1. Alteration of neural action potential patterns by axonal stimulation: the importance of stimulus location

    PubMed Central

    Crago, Patrick E; Makowski, Nathan S

    2014-01-01

    Objective Stimulation of peripheral nerves is often superimposed on ongoing motor and sensory activity in the same axons, without a quantitative model of the net action potential train at the axon endpoint. Approach We develop a model of action potential patterns elicited by superimposing constant frequency axonal stimulation on the action potentials arriving from a physiologically activated neural source. The model includes interactions due to collision block, resetting of the neural impulse generator, and the refractory period of the axon at the point of stimulation. Main Results Both the mean endpoint firing rate and the probability distribution of the action potential firing periods depend strongly on the relative firing rates of the two sources and the intersite conduction time between them. When the stimulus rate exceeds the neural rate, neural action potentials do not reach the endpoint and the rate of endpoint action potentials is the same as the stimulus rate, regardless of the intersite conduction time. However, when the stimulus rate is less than the neural rate, and the intersite conduction time is short, the two rates partially sum. Increases in stimulus rate produce non-monotonic increases in endpoint rate and continuously increasing block of neurally generated action potentials. Rate summation is reduced and more neural action potentials are blocked as the intersite conduction time increases.. At long intersite conduction times, the endpoint rate simplifies to being the maximum of either the neural or the stimulus rate. Significance This study highlights the potential of increasing the endpoint action potential rate and preserving neural information transmission by low rate stimulation with short intersite conduction times. Intersite conduction times can be decreased with proximal stimulation sites for muscles and distal stimulation sites for sensory endings. The model provides a basis for optimizing experiments and designing neuroprosthetic

  2. Determination of cable parameters in skeletal muscle fibres during repetitive firing of action potentials

    PubMed Central

    Riisager, Anders; Duehmke, Rudy; Nielsen, Ole Bækgaard; Huang, Christopher L; Pedersen, Thomas Holm

    2014-01-01

    Recent studies in rat muscle fibres show that repetitive firing of action potentials causes changes in fibre resting membrane conductance (Gm) that reflect regulation of ClC-1 Cl− and KATP K+ ion channels. Methodologically, these findings were obtained by inserting two microelectrodes at close proximity in the same fibres enabling measurements of fibre input resistance (Rin) in between action potential trains. Since the fibre length constant (λ) could not be determined, however, the calculation of Gm relied on the assumptions that the specific cytosolic resistivity (Ri) and muscle fibre volume remained constant during the repeated action potential firing. Here we present a three-microelectrode technique that enables determinations of multiple cable parameters in action potential-firing fibres including Rin and λ as well as waveform and conduction velocities of fully propagating action potentials. It is shown that in both rat and mouse extensor digitorum longus (EDL) fibres, action potential firing leads to substantial changes in both muscle fibre volume and Ri. The analysis also showed, however, that regardless of these changes, rat and mouse EDL fibres both exhibited initial decreases in Gm that were eventually followed by a ∼3-fold, fully reversible increase in Gm after the firing of 1450–1800 action potentials. Using this three-electrode method we further show that the latter rise in Gm was closely associated with excitation failures and loss of action potential signal above −20 mV. PMID:25128573

  3. Action potentials drive body wall muscle contractions in Caenorhabditis elegans

    PubMed Central

    Gao, Shangbang; Zhen, Mei

    2011-01-01

    The sinusoidal locomotion exhibited by Caenorhabditis elegans predicts a tight regulation of contractions and relaxations of its body wall muscles. Vertebrate skeletal muscle contractions are driven by voltage-gated sodium channel–dependent action potentials. How coordinated motor outputs are regulated in C. elegans, which does not have voltage-gated sodium channels, remains unknown. Here, we show that C. elegans body wall muscles fire all-or-none, calcium-dependent action potentials that are driven by the L-type voltage-gated calcium and Kv1 voltage-dependent potassium channels. We further demonstrate that the excitatory and inhibitory motoneuron activities regulate the frequency of action potentials to coordinate muscle contraction and relaxation, respectively. This study provides direct evidence for the dual-modulatory model of the C. elegans motor circuit; moreover, it reveals a mode of motor control in which muscle cells integrate graded inputs of the nervous system and respond with all-or-none electrical signals. PMID:21248227

  4. Determination of cable parameters in skeletal muscle fibres during repetitive firing of action potentials.

    PubMed

    Riisager, Anders; Duehmke, Rudy; Nielsen, Ole Bækgaard; Huang, Christopher L; Pedersen, Thomas Holm

    2014-10-15

    Recent studies in rat muscle fibres show that repetitive firing of action potentials causes changes in fibre resting membrane conductance (Gm) that reflect regulation of ClC-1 Cl(-) and KATP K(+) ion channels. Methodologically, these findings were obtained by inserting two microelectrodes at close proximity in the same fibres enabling measurements of fibre input resistance (Rin) in between action potential trains. Since the fibre length constant (λ) could not be determined, however, the calculation of Gm relied on the assumptions that the specific cytosolic resistivity (Ri) and muscle fibre volume remained constant during the repeated action potential firing. Here we present a three-microelectrode technique that enables determinations of multiple cable parameters in action potential-firing fibres including Rin and λ as well as waveform and conduction velocities of fully propagating action potentials. It is shown that in both rat and mouse extensor digitorum longus (EDL) fibres, action potential firing leads to substantial changes in both muscle fibre volume and Ri. The analysis also showed, however, that regardless of these changes, rat and mouse EDL fibres both exhibited initial decreases in Gm that were eventually followed by a ∼3-fold, fully reversible increase in Gm after the firing of 1450-1800 action potentials. Using this three-electrode method we further show that the latter rise in Gm was closely associated with excitation failures and loss of action potential signal above -20 mV. © 2014 The Authors. The Journal of Physiology © 2014 The Physiological Society.

  5. Understanding the electrical behavior of the action potential in terms of elementary electrical sources.

    PubMed

    Rodriguez-Falces, Javier

    2015-03-01

    A concept of major importance in human electrophysiology studies is the process by which activation of an excitable cell results in a rapid rise and fall of the electrical membrane potential, the so-called action potential. Hodgkin and Huxley proposed a model to explain the ionic mechanisms underlying the formation of action potentials. However, this model is unsuitably complex for teaching purposes. In addition, the Hodgkin and Huxley approach describes the shape of the action potential only in terms of ionic currents, i.e., it is unable to explain the electrical significance of the action potential or describe the electrical field arising from this source using basic concepts of electromagnetic theory. The goal of the present report was to propose a new model to describe the electrical behaviour of the action potential in terms of elementary electrical sources (in particular, dipoles). The efficacy of this model was tested through a closed-book written exam. The proposed model increased the ability of students to appreciate the distributed character of the action potential and also to recognize that this source spreads out along the fiber as function of space. In addition, the new approach allowed students to realize that the amplitude and sign of the extracellular electrical potential arising from the action potential are determined by the spatial derivative of this intracellular source. The proposed model, which incorporates intuitive graphical representations, has improved students' understanding of the electrical potentials generated by bioelectrical sources and has heightened their interest in bioelectricity. Copyright © 2015 The American Physiological Society.

  6. Synaptic depolarization is more effective than back-propagating action potentials during induction of associative long-term potentiation in hippocampal pyramidal neurons.

    PubMed

    Hardie, Jason; Spruston, Nelson

    2009-03-11

    Long-term potentiation (LTP) requires postsynaptic depolarization that can result from EPSPs paired with action potentials or larger EPSPs that trigger dendritic spikes. We explored the relative contribution of these sources of depolarization to LTP induction during synaptically driven action potential firing in hippocampal CA1 pyramidal neurons. Pairing of a weak test input with a strong input resulted in large LTP (approximately 75% increase) when the weak and strong inputs were both located in the apical dendrites. This form of LTP did not require somatic action potentials. When the strong input was located in the basal dendrites, the resulting LTP was smaller (< or =25% increase). Pairing the test input with somatically evoked action potentials mimicked this form of LTP. Thus, back-propagating action potentials may contribute to modest LTP, but local synaptic depolarization and/or dendritic spikes mediate a stronger form of LTP that requires spatial proximity of the associated synaptic inputs.

  7. Rosewood oil induces sedation and inhibits compound action potential in rodents.

    PubMed

    de Almeida, Reinaldo Nóbrega; Araújo, Demétrius Antonio Machado; Gonçalves, Juan Carlos Ramos; Montenegro, Fabrícia Costa; de Sousa, Damião Pergentino; Leite, José Roberto; Mattei, Rita; Benedito, Marco Antonio Campana; de Carvalho, José Gilberto Barbosa; Cruz, Jader Santos; Maia, José Guilherme Soares

    2009-07-30

    Aniba rosaeodora is an aromatic plant which has been used in Brazil folk medicine due to its sedative effect. Therefore, the purpose of the present study was to evaluate the sedative effect of linalool-rich rosewood oil in mice. In addition we sought to investigate the linalool-rich oil effects on the isolated nerve using the single sucrose-gap technique. Sedative effect was determined by measuring the potentiation of the pentobarbital-induced sleeping time. The compound action potential amplitude was evaluated as a way to detect changes in excitability of the isolated nerve. The results showed that administration of rosewood oil at the doses of 200 and 300 mg/kg significantly decreased latency and increased the duration of sleeping time. On the other hand, the dose of 100 mg/kg potentiated significantly the pentobarbital action decreasing pentobarbital latency time and increasing pentobarbital sleeping time. In addition, the effect of linalool-rich rosewood oil on the isolated nerve of the rat was also investigated through the single sucrose-gap technique. The amplitude of the action potential decreased almost 100% when it was incubated for 30 min at 100 microg/ml. From this study, it is suggested a sedative effect of linalool-rich rosewood oil that could, at least in part, be explained by the reduction in action potential amplitude that provokes a decrease in neuronal excitability.

  8. Improving Cardiac Action Potential Measurements: 2D and 3D Cell Culture.

    PubMed

    Daily, Neil J; Yin, Yue; Kemanli, Pinar; Ip, Brian; Wakatsuki, Tetsuro

    2015-11-01

    Progress in the development of assays for measuring cardiac action potential is crucial for the discovery of drugs for treating cardiac disease and assessing cardiotoxicity. Recently, high-throughput methods for assessing action potential using induced pluripotent stem cell (iPSC) derived cardiomyocytes in both two-dimensional monolayer cultures and three-dimensional tissues have been developed. We describe an improved method for assessing cardiac action potential using an ultra-fast cost-effective plate reader with commercially available dyes. Our methods improve dramatically the detection of the fluorescence signal from these dyes and make way for the development of more high-throughput methods for cardiac drug discovery and cardiotoxicity.

  9. Ionic channels underlying the ventricular action potential in zebrafish embryo.

    PubMed

    Alday, Aintzane; Alonso, Hiart; Gallego, Monica; Urrutia, Janire; Letamendia, Ainhoa; Callol, Carles; Casis, Oscar

    2014-06-01

    Over the last years zebrafish has become a popular model in the study of cardiac physiology, pathology and pharmacology. Recently, the application of the 3Rs regulation and the characteristics of the embryo have reduced the use of adult zebrafish use in many studies. However, the zebrafish embryo cardiac physiology is poorly characterized since most works have used indirect techniques and direct recordings of cardiac action potential and ionic currents are scarce. In order to optimize the zebrafish embryo model, we used electrophysiological, pharmacological and immunofluorescence tools to identify the characteristics and the ionic channels involved in the ventricular action potentials of zebrafish embryos. The application of Na(+) or T-type Ca(+2) channel blockers eliminated the cardiac electrical activity, indicating that the action potential upstroke depends on Na(+) and T-type Ca(+2) currents. The plateau phase depends on L-type Ca(+2) channels since it is abolished by specific blockade. The direct channel blockade indicates that the action potential repolarization and diastolic potential depends on ERG K(+) channels. The presence in the embryonic heart of the Nav1.5, Cav1.2, Cav3.2 and ERG channels was also confirmed by immunofluorescence, while the absence of effect of specific blockers and immunostaining indicate that two K(+) repolarizing currents present in human heart, Ito and IKs, are absent in the embryonic zebrafish heart. Our results describe the ionic channels present and its role in the zebrafish embryo heart and support the use of zebrafish embryos to study human diseases and their use for drug testing. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. Warm Body Temperature Facilitates Energy Efficient Cortical Action Potentials

    PubMed Central

    Yu, Yuguo; Hill, Adam P.; McCormick, David A.

    2012-01-01

    The energy efficiency of neural signal transmission is important not only as a limiting factor in brain architecture, but it also influences the interpretation of functional brain imaging signals. Action potential generation in mammalian, versus invertebrate, axons is remarkably energy efficient. Here we demonstrate that this increase in energy efficiency is due largely to a warmer body temperature. Increases in temperature result in an exponential increase in energy efficiency for single action potentials by increasing the rate of Na+ channel inactivation, resulting in a marked reduction in overlap of the inward Na+, and outward K+, currents and a shortening of action potential duration. This increase in single spike efficiency is, however, counterbalanced by a temperature-dependent decrease in the amplitude and duration of the spike afterhyperpolarization, resulting in a nonlinear increase in the spike firing rate, particularly at temperatures above approximately 35°C. Interestingly, the total energy cost, as measured by the multiplication of total Na+ entry per spike and average firing rate in response to a constant input, reaches a global minimum between 37–42°C. Our results indicate that increases in temperature result in an unexpected increase in energy efficiency, especially near normal body temperature, thus allowing the brain to utilize an energy efficient neural code. PMID:22511855

  11. Direct detection of a single evoked action potential with MRS in Lumbricus terrestris.

    PubMed

    Poplawsky, Alexander J; Dingledine, Raymond; Hu, Xiaoping P

    2012-01-01

    Functional MRI (fMRI) measures neural activity indirectly by detecting the signal change associated with the hemodynamic response following brain activation. In order to alleviate the temporal and spatial specificity problems associated with fMRI, a number of attempts have been made to detect neural magnetic fields (NMFs) with MRI directly, but have thus far provided conflicting results. In this study, we used MR to detect axonal NMFs in the median giant fiber of the earthworm, Lumbricus terrestris, by examining the free induction decay (FID) with a sampling interval of 0.32 ms. The earthworm nerve cords were isolated from the vasculature and stimulated at the threshold of action potential generation. FIDs were acquired shortly after the stimulation, and simultaneous field potential recordings identified the presence or absence of single evoked action potentials. FIDs acquired when the stimulus did not evoke an action potential were summed as background. The phase of the background-subtracted FID exhibited a systematic change, with a peak phase difference of (-1.2 ± 0.3) × 10(-5) radians occurring at a time corresponding to the timing of the action potential. In addition, we calculated the possible changes in the FID magnitude and phase caused by a simulated action potential using a volume conductor model. The measured phase difference matched the theoretical prediction well in both amplitude and temporal characteristics. This study provides the first evidence for the direct detection of a magnetic field from an evoked action potential using MR. Copyright © 2011 John Wiley & Sons, Ltd.

  12. Relationship between size and latency of action potentials in human muscle sympathetic nerve activity.

    PubMed

    Salmanpour, Aryan; Brown, Lyndon J; Steinback, Craig D; Usselman, Charlotte W; Goswami, Ruma; Shoemaker, J Kevin

    2011-06-01

    We employed a novel action potential detection and classification technique to study the relationship between the recruitment of sympathetic action potentials (i.e., neurons) and the size of integrated sympathetic bursts in human muscle sympathetic nerve activity (MSNA). Multifiber postganglionic sympathetic nerve activity from the common fibular nerve was collected using microneurography in 10 healthy subjects at rest and during activation of sympathetic outflow using lower body negative pressure (LBNP). Burst occurrence increased with LBNP. Integrated burst strength (size) varied from 0.22 ± 0.07 V at rest to 0.28 ± 0.09 V during LBNP. Sympathetic burst size (i.e., peak height) was directly related to the number of action potentials within a sympathetic burst both at baseline (r = 0.75 ± 0.13; P < 0.001) and LBNP (r = 0.75 ± 0.12; P < 0.001). Also, the amplitude of detected action potentials within sympathetic bursts was directly related to the increased burst size at both baseline (r = 0.59 ± 0.16; P < 0.001) and LBNP (r = 0.61 ± 0.12; P < 0.001). In addition, the number of detected action potentials and the number of distinct action potential clusters within a given sympathetic burst were correlated at baseline (r = 0.7 ± 0.1; P < 0.001) and during LBNP (r = 0.74 ± 0.03; P < 0.001). Furthermore, action potential latency (i.e., an inverse index of neural conduction velocity) was decreased as a function of action potential size at baseline and LBNP. LBNP did not change the number of action potentials and unique clusters per sympathetic burst. It was concluded that there exists a hierarchical pattern of recruitment of additional faster conducting neurons of larger amplitude as the sympathetic bursts become stronger (i.e., larger amplitude bursts). This fundamental pattern was evident at rest and was not altered by the level of baroreceptor unloading applied in this study.

  13. Sodium and calcium currents shape action potentials in immature mouse inner hair cells

    PubMed Central

    Marcotti, Walter; Johnson, Stuart L; Rüsch, Alfons; Kros, Corné J

    2003-01-01

    Before the onset of hearing at postnatal day 12, mouse inner hair cells (IHCs) produce spontaneous and evoked action potentials. These spikes are likely to induce neurotransmitter release onto auditory nerve fibres. Since immature IHCs express both α1D (Cav1.3) Ca2+ and Na+ currents that activate near the resting potential, we examined whether these two conductances are involved in shaping the action potentials. Both had extremely rapid activation kinetics, followed by fast and complete voltage-dependent inactivation for the Na+ current, and slower, partially Ca2+-dependent inactivation for the Ca2+ current. Only the Ca2+ current is necessary for spontaneous and induced action potentials, and 29 % of cells lacked a Na+ current. The Na+ current does, however, shorten the time to reach the action-potential threshold, whereas the Ca2+ current is mainly involved, together with the K+ currents, in determining the speed and size of the spikes. Both currents increased in size up to the end of the first postnatal week. After this, the Ca2+ current reduced to about 30 % of its maximum size and persisted in mature IHCs. The Na+ current was downregulated around the onset of hearing, when the spiking is also known to disappear. Although the Na+ current was observed as early as embryonic day 16.5, its role in action-potential generation was only evident from just after birth, when the resting membrane potential became sufficiently negative to remove a sizeable fraction of the inactivation (half inactivation was at −71 mV). The size of both currents was positively correlated with the developmental change in action-potential frequency. PMID:12937295

  14. Channel sialic acids limit hERG channel activity during the ventricular action potential.

    PubMed

    Norring, Sarah A; Ednie, Andrew R; Schwetz, Tara A; Du, Dongping; Yang, Hui; Bennett, Eric S

    2013-02-01

    Activity of human ether-a-go-go-related gene (hERG) 1 voltage-gated K(+) channels is responsible for portions of phase 2 and phase 3 repolarization of the human ventricular action potential. Here, we questioned whether and how physiologically and pathophysiologically relevant changes in surface N-glycosylation modified hERG channel function. Voltage-dependent hERG channel gating and activity were evaluated as expressed in a set of Chinese hamster ovary (CHO) cell lines under conditions of full glycosylation, no sialylation, no complex N-glycans, and following enzymatic deglycosylation of surface N-glycans. For each condition of reduced glycosylation, hERG channel steady-state activation and inactivation relationships were shifted linearly by significant depolarizing ∼9 and ∼18 mV, respectively. The hERG window current increased significantly by 50-150%, and the peak shifted by a depolarizing ∼10 mV. There was no significant change in maximum hERG current density. Deglycosylated channels were significantly more active (20-80%) than glycosylated controls during phases 2 and 3 of action potential clamp protocols. Simulations of hERG current and ventricular action potentials corroborated experimental data and predicted reduced sialylation leads to a 50-70-ms decrease in action potential duration. The data describe a novel mechanism by which hERG channel gating is modulated through physiologically and pathophysiologically relevant changes in N-glycosylation; reduced channel sialylation increases hERG channel activity during the action potential, thereby increasing the rate of action potential repolarization.

  15. Crataegus extract prolongs action potential duration in guinea-pig papillary muscle.

    PubMed

    Müller, A; Linke, W; Zhao, Y; Klaus, W

    1996-11-01

    Crataegus extract is used in cardiology for the treatment of moderate heart failure (NYHA II). Recently it was shown that Crataegus extract prolongs the refractory period in isolated perfused guinea pig hearts. In order to find out what mechanism is responsible for this prolongation of refractory period, we investigated the effects of Crataegus extract (LI 132) on the action potential of guinea pig papillary muscle with the help of conventional microelectrode techniques. Crataegus extract, when put in a concentration (10 mg/l) capable of inducing an inotropic effect of about 20%, significantly increased action potential duration at all investigated levels of repolarisation. Maximum prolongation was 8.5±2.3 ms, 12.5±2.6 ms and 11.7±2.9 ms at 20%, 50% and 90% repolarisation, respectively (control APD(90): 172±4 ms). Experiments on the time course of recovery of the maximum upstroke velocity (V(max)) of the action potential revealed that Crataegus extract increased the time constant of recovery of V(max) from 8.80±2.33 ms to 22.60±5.77 ms, indicating a weak Class I-like antiarrhythmic action. In addition, we observed a small reduction in V(max). In summary, our results show that Crataegus extract prolongs action potential duration and delays recovery of V(max). We, therefore, suggest that Crataegus extract possesses certain antiarrhythmic properties. Copyright © 1996 Gustav Fischer Verlag · Stuttgart · Jena · New York. Published by Elsevier GmbH.. All rights reserved.

  16. A Parametric Computational Model of the Action Potential of Pacemaker Cells.

    PubMed

    Ai, Weiwei; Patel, Nitish D; Roop, Partha S; Malik, Avinash; Andalam, Sidharta; Yip, Eugene; Allen, Nathan; Trew, Mark L

    2018-01-01

    A flexible, efficient, and verifiable pacemaker cell model is essential to the design of real-time virtual hearts that can be used for closed-loop validation of cardiac devices. A new parametric model of pacemaker action potential is developed to address this need. The action potential phases are modeled using hybrid automaton with one piecewise-linear continuous variable. The model can capture rate-dependent dynamics, such as action potential duration restitution, conduction velocity restitution, and overdrive suppression by incorporating nonlinear update functions. Simulated dynamics of the model compared well with previous models and clinical data. The results show that the parametric model can reproduce the electrophysiological dynamics of a variety of pacemaker cells, such as sinoatrial node, atrioventricular node, and the His-Purkinje system, under varying cardiac conditions. This is an important contribution toward closed-loop validation of cardiac devices using real-time heart models.

  17. Body posture modulates action perception.

    PubMed

    Zimmermann, Marius; Toni, Ivan; de Lange, Floris P

    2013-04-03

    Recent studies have highlighted cognitive and neural similarities between planning and perceiving actions. Given that action planning involves a simulation of potential action plans that depends on the actor's body posture, we reasoned that perceiving actions may also be influenced by one's body posture. Here, we test whether and how this influence occurs by measuring behavioral and cerebral (fMRI) responses in human participants predicting goals of observed actions, while manipulating postural congruency between their own body posture and postures of the observed agents. Behaviorally, predicting action goals is facilitated when the body posture of the observer matches the posture achieved by the observed agent at the end of his action (action's goal posture). Cerebrally, this perceptual postural congruency effect modulates activity in a portion of the left intraparietal sulcus that has previously been shown to be involved in updating neural representations of one's own limb posture during action planning. This intraparietal area showed stronger responses when the goal posture of the observed action did not match the current body posture of the observer. These results add two novel elements to the notion that perceiving actions relies on the same predictive mechanism as planning actions. First, the predictions implemented by this mechanism are based on the current physical configuration of the body. Second, during both action planning and action observation, these predictions pertain to the goal state of the action.

  18. Euler and Potential Experiment/CFD Correlations for a Transport and Two Delta-Wing Configurations

    NASA Technical Reports Server (NTRS)

    Hicks, R. M.; Cliff, S. E.; Melton, J. E.; Langhi, R. G.; Goodsell, A. M.; Robertson, D. D.; Moyer, S. A.

    1990-01-01

    A selection of successes and failures of Computational Fluid Dynamics (CFD) is discussed. Experiment/CFD correlations involving full potential and Euler computations of the aerodynamic characteristics of four commercial transport wings and two low aspect ratio, delta wing configurations are shown. The examples consist of experiment/CFD comparisons for aerodynamic forces, moments, and pressures. Navier-Stokes equations are not considered.

  19. Cell-type-dependent action potentials and voltage-gated currents in mouse fungiform taste buds.

    PubMed

    Kimura, Kenji; Ohtubo, Yoshitaka; Tateno, Katsumi; Takeuchi, Keita; Kumazawa, Takashi; Yoshii, Kiyonori

    2014-01-01

    Taste receptor cells fire action potentials in response to taste substances to trigger non-exocytotic neurotransmitter release in type II cells and exocytotic release in type III cells. We investigated possible differences between these action potentials fired by mouse taste receptor cells using in situ whole-cell recordings, and subsequently we identified their cell types immunologically with cell-type markers, an IP3 receptor (IP3 R3) for type II cells and a SNARE protein (SNAP-25) for type III cells. Cells not immunoreactive to these antibodies were examined as non-IRCs. Here, we show that type II cells and type III cells fire action potentials using different ionic mechanisms, and that non-IRCs also fire action potentials with either of the ionic mechanisms. The width of action potentials was significantly narrower and their afterhyperpolarization was deeper in type III cells than in type II cells. Na(+) current density was similar in type II cells and type III cells, but it was significantly smaller in non-IRCs than in the others. Although outwardly rectifying current density was similar between type II cells and type III cells, tetraethylammonium (TEA) preferentially suppressed the density in type III cells and the majority of non-IRCs. Our mathematical model revealed that the shape of action potentials depended on the ratio of TEA-sensitive current density and TEA-insensitive current one. The action potentials of type II cells and type III cells under physiological conditions are discussed. © 2013 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  20. Autonomous initiation and propagation of action potentials in neurons of the subthalamic nucleus.

    PubMed

    Atherton, Jeremy F; Wokosin, David L; Ramanathan, Sankari; Bevan, Mark D

    2008-12-01

    The activity of the subthalamic nucleus (STN) is intimately related to movement and is generated, in part, by voltage-dependent Na(+) (Na(v)) channels that drive autonomous firing. In order to determine the principles underlying the initiation and propagation of action potentials in STN neurons, 2-photon laser scanning microscopy was used to guide tight-seal whole-cell somatic and loose-seal cell-attached axonal/dendritic patch-clamp recordings and compartment-selective ion channel manipulation in rat brain slices. Action potentials were first detected in a region that corresponded most closely to the unmyelinated axon initial segment, as defined by Golgi and ankyrin G labelling. Following initiation, action potentials propagated reliably into axonal and somatodendritic compartments with conduction velocities of approximately 5 m s(-1) and approximately 0.7 m s(-1), respectively. Action potentials generated by neurons with axons truncated within or beyond the axon initial segment were not significantly different. However, axon initial segment and somatic but not dendritic or more distal axonal application of low [Na(+)] ACSF or the selective Na(v) channel blocker tetrodotoxin consistently depolarized action potential threshold. Finally, somatodendritic but not axonal application of GABA evoked large, rapid inhibitory currents in concordance with electron microscopic analyses, which revealed that the somatodendritic compartment was the principal target of putative inhibitory inputs. Together the data are consistent with the conclusions that in STN neurons the axon initial segment and soma express an excess of Na(v) channels for the generation of autonomous activity, while synaptic activation of somatodendritic GABA(A) receptors regulates the axonal initiation of action potentials.

  1. Autonomous initiation and propagation of action potentials in neurons of the subthalamic nucleus

    PubMed Central

    Atherton, Jeremy F; Wokosin, David L; Ramanathan, Sankari; Bevan, Mark D

    2008-01-01

    The activity of the subthalamic nucleus (STN) is intimately related to movement and is generated, in part, by voltage-dependent Na+ (Nav) channels that drive autonomous firing. In order to determine the principles underlying the initiation and propagation of action potentials in STN neurons, 2-photon laser scanning microscopy was used to guide tight-seal whole-cell somatic and loose-seal cell-attached axonal/dendritic patch-clamp recordings and compartment-selective ion channel manipulation in rat brain slices. Action potentials were first detected in a region that corresponded most closely to the unmyelinated axon initial segment, as defined by Golgi and ankyrin G labelling. Following initiation, action potentials propagated reliably into axonal and somatodendritic compartments with conduction velocities of ∼5 m s−1 and ∼0.7 m s−1, respectively. Action potentials generated by neurons with axons truncated within or beyond the axon initial segment were not significantly different. However, axon initial segment and somatic but not dendritic or more distal axonal application of low [Na+] ACSF or the selective Nav channel blocker tetrodotoxin consistently depolarized action potential threshold. Finally, somatodendritic but not axonal application of GABA evoked large, rapid inhibitory currents in concordance with electron microscopic analyses, which revealed that the somatodendritic compartment was the principal target of putative inhibitory inputs. Together the data are consistent with the conclusions that in STN neurons the axon initial segment and soma express an excess of Nav channels for the generation of autonomous activity, while synaptic activation of somatodendritic GABAA receptors regulates the axonal initiation of action potentials. PMID:18832425

  2. Imaging Action Potential in Single Mammalian Neurons by Tracking the Accompanying Sub-Nanometer Mechanical Motion.

    PubMed

    Yang, Yunze; Liu, Xian-Wei; Wang, Hui; Yu, Hui; Guan, Yan; Wang, Shaopeng; Tao, Nongjian

    2018-03-28

    Action potentials in neurons have been studied traditionally by intracellular electrophysiological recordings and more recently by the fluorescence detection methods. Here we describe a label-free optical imaging method that can measure mechanical motion in single cells with a sub-nanometer detection limit. Using the method, we have observed sub-nanometer mechanical motion accompanying the action potential in single mammalian neurons by averaging the repeated action potential spikes. The shape and width of the transient displacement are similar to those of the electrically recorded action potential, but the amplitude varies from neuron to neuron, and from one region of a neuron to another, ranging from 0.2-0.4 nm. The work indicates that action potentials may be studied noninvasively in single mammalian neurons by label-free imaging of the accompanying sub-nanometer mechanical motion.

  3. Noise Enhances Action Potential Generation in Mouse Sensory Neurons via Stochastic Resonance

    PubMed Central

    Onorato, Irene; D'Alessandro, Giuseppina; Di Castro, Maria Amalia; Renzi, Massimiliano; Dobrowolny, Gabriella; Musarò, Antonio; Salvetti, Marco; Limatola, Cristina; Crisanti, Andrea; Grassi, Francesca

    2016-01-01

    Noise can enhance perception of tactile and proprioceptive stimuli by stochastic resonance processes. However, the mechanisms underlying this general phenomenon remain to be characterized. Here we studied how externally applied noise influences action potential firing in mouse primary sensory neurons of dorsal root ganglia, modelling a basic process in sensory perception. Since noisy mechanical stimuli may cause stochastic fluctuations in receptor potential, we examined the effects of sub-threshold depolarizing current steps with superimposed random fluctuations. We performed whole cell patch clamp recordings in cultured neurons of mouse dorsal root ganglia. Noise was added either before and during the step, or during the depolarizing step only, to focus onto the specific effects of external noise on action potential generation. In both cases, step + noise stimuli triggered significantly more action potentials than steps alone. The normalized power norm had a clear peak at intermediate noise levels, demonstrating that the phenomenon is driven by stochastic resonance. Spikes evoked in step + noise trials occur earlier and show faster rise time as compared to the occasional ones elicited by steps alone. These data suggest that external noise enhances, via stochastic resonance, the recruitment of transient voltage-gated Na channels, responsible for action potential firing in response to rapid step-wise depolarizing currents. PMID:27525414

  4. Noise Enhances Action Potential Generation in Mouse Sensory Neurons via Stochastic Resonance.

    PubMed

    Onorato, Irene; D'Alessandro, Giuseppina; Di Castro, Maria Amalia; Renzi, Massimiliano; Dobrowolny, Gabriella; Musarò, Antonio; Salvetti, Marco; Limatola, Cristina; Crisanti, Andrea; Grassi, Francesca

    2016-01-01

    Noise can enhance perception of tactile and proprioceptive stimuli by stochastic resonance processes. However, the mechanisms underlying this general phenomenon remain to be characterized. Here we studied how externally applied noise influences action potential firing in mouse primary sensory neurons of dorsal root ganglia, modelling a basic process in sensory perception. Since noisy mechanical stimuli may cause stochastic fluctuations in receptor potential, we examined the effects of sub-threshold depolarizing current steps with superimposed random fluctuations. We performed whole cell patch clamp recordings in cultured neurons of mouse dorsal root ganglia. Noise was added either before and during the step, or during the depolarizing step only, to focus onto the specific effects of external noise on action potential generation. In both cases, step + noise stimuli triggered significantly more action potentials than steps alone. The normalized power norm had a clear peak at intermediate noise levels, demonstrating that the phenomenon is driven by stochastic resonance. Spikes evoked in step + noise trials occur earlier and show faster rise time as compared to the occasional ones elicited by steps alone. These data suggest that external noise enhances, via stochastic resonance, the recruitment of transient voltage-gated Na channels, responsible for action potential firing in response to rapid step-wise depolarizing currents.

  5. Automatic selection of atomic fingerprints and reference configurations for machine-learning potentials

    NASA Astrophysics Data System (ADS)

    Imbalzano, Giulio; Anelli, Andrea; Giofré, Daniele; Klees, Sinja; Behler, Jörg; Ceriotti, Michele

    2018-06-01

    Machine learning of atomic-scale properties is revolutionizing molecular modeling, making it possible to evaluate inter-atomic potentials with first-principles accuracy, at a fraction of the costs. The accuracy, speed, and reliability of machine learning potentials, however, depend strongly on the way atomic configurations are represented, i.e., the choice of descriptors used as input for the machine learning method. The raw Cartesian coordinates are typically transformed in "fingerprints," or "symmetry functions," that are designed to encode, in addition to the structure, important properties of the potential energy surface like its invariances with respect to rotation, translation, and permutation of like atoms. Here we discuss automatic protocols to select a number of fingerprints out of a large pool of candidates, based on the correlations that are intrinsic to the training data. This procedure can greatly simplify the construction of neural network potentials that strike the best balance between accuracy and computational efficiency and has the potential to accelerate by orders of magnitude the evaluation of Gaussian approximation potentials based on the smooth overlap of atomic positions kernel. We present applications to the construction of neural network potentials for water and for an Al-Mg-Si alloy and to the prediction of the formation energies of small organic molecules using Gaussian process regression.

  6. Cortical Interneuron Subtypes Vary in Their Axonal Action Potential Properties

    PubMed Central

    Casale, Amanda E.; Foust, Amanda J.; Bal, Thierry

    2015-01-01

    The role of interneurons in cortical microcircuits is strongly influenced by their passive and active electrical properties. Although different types of interneurons exhibit unique electrophysiological properties recorded at the soma, it is not yet clear whether these differences are also manifested in other neuronal compartments. To address this question, we have used voltage-sensitive dye to image the propagation of action potentials into the fine collaterals of axons and dendrites in two of the largest cortical interneuron subtypes in the mouse: fast-spiking interneurons, which are typically basket or chandelier neurons; and somatostatin containing interneurons, which are typically regular spiking Martinotti cells. We found that fast-spiking and somatostatin-expressing interneurons differed in their electrophysiological characteristics along their entire dendrosomatoaxonal extent. The action potentials generated in the somata and axons, including axon collaterals, of somatostatin-expressing interneurons are significantly broader than those generated in the same compartments of fast-spiking inhibitory interneurons. In addition, action potentials back-propagated into the dendrites of somatostatin-expressing interneurons much more readily than fast-spiking interneurons. Pharmacological investigations suggested that axonal action potential repolarization in both cell types depends critically upon Kv1 channels, whereas the axonal and somatic action potentials of somatostatin-expressing interneurons also depend on BK Ca2+-activated K+ channels. These results indicate that the two broad classes of interneurons studied here have expressly different subcellular physiological properties, allowing them to perform unique computational roles in cortical circuit operations. SIGNIFICANCE STATEMENT Neurons in the cerebral cortex are of two major types: excitatory and inhibitory. The proper balance of excitation and inhibition in the brain is critical for its operation. Neurons

  7. Cortical Interneuron Subtypes Vary in Their Axonal Action Potential Properties.

    PubMed

    Casale, Amanda E; Foust, Amanda J; Bal, Thierry; McCormick, David A

    2015-11-25

    The role of interneurons in cortical microcircuits is strongly influenced by their passive and active electrical properties. Although different types of interneurons exhibit unique electrophysiological properties recorded at the soma, it is not yet clear whether these differences are also manifested in other neuronal compartments. To address this question, we have used voltage-sensitive dye to image the propagation of action potentials into the fine collaterals of axons and dendrites in two of the largest cortical interneuron subtypes in the mouse: fast-spiking interneurons, which are typically basket or chandelier neurons; and somatostatin containing interneurons, which are typically regular spiking Martinotti cells. We found that fast-spiking and somatostatin-expressing interneurons differed in their electrophysiological characteristics along their entire dendrosomatoaxonal extent. The action potentials generated in the somata and axons, including axon collaterals, of somatostatin-expressing interneurons are significantly broader than those generated in the same compartments of fast-spiking inhibitory interneurons. In addition, action potentials back-propagated into the dendrites of somatostatin-expressing interneurons much more readily than fast-spiking interneurons. Pharmacological investigations suggested that axonal action potential repolarization in both cell types depends critically upon Kv1 channels, whereas the axonal and somatic action potentials of somatostatin-expressing interneurons also depend on BK Ca(2+)-activated K(+) channels. These results indicate that the two broad classes of interneurons studied here have expressly different subcellular physiological properties, allowing them to perform unique computational roles in cortical circuit operations. Neurons in the cerebral cortex are of two major types: excitatory and inhibitory. The proper balance of excitation and inhibition in the brain is critical for its operation. Neurons contain three main

  8. Calcium-Induced Calcium Release during Action Potential Firing in Developing Inner Hair Cells

    PubMed Central

    Iosub, Radu; Avitabile, Daniele; Grant, Lisa; Tsaneva-Atanasova, Krasimira; Kennedy, Helen J.

    2015-01-01

    In the mature auditory system, inner hair cells (IHCs) convert sound-induced vibrations into electrical signals that are relayed to the central nervous system via auditory afferents. Before the cochlea can respond to normal sound levels, developing IHCs fire calcium-based action potentials that disappear close to the onset of hearing. Action potential firing triggers transmitter release from the immature IHC that in turn generates experience-independent firing in auditory neurons. These early signaling events are thought to be essential for the organization and development of the auditory system and hair cells. A critical component of the action potential is the rise in intracellular calcium that activates both small conductance potassium channels essential during membrane repolarization, and triggers transmitter release from the cell. Whether this calcium signal is generated by calcium influx or requires calcium-induced calcium release (CICR) is not yet known. IHCs can generate CICR, but to date its physiological role has remained unclear. Here, we used high and low concentrations of ryanodine to block or enhance CICR to determine whether calcium release from intracellular stores affected action potential waveform, interspike interval, or changes in membrane capacitance during development of mouse IHCs. Blocking CICR resulted in mixed action potential waveforms with both brief and prolonged oscillations in membrane potential and intracellular calcium. This mixed behavior is captured well by our mathematical model of IHC electrical activity. We perform two-parameter bifurcation analysis of the model that predicts the dependence of IHCs firing patterns on the level of activation of two parameters, the SK2 channels activation and CICR rate. Our data show that CICR forms an important component of the calcium signal that shapes action potentials and regulates firing patterns, but is not involved directly in triggering exocytosis. These data provide important insights

  9. Action potential bursts in central snail neurons elicited by paeonol: roles of ionic currents

    PubMed Central

    Chen, Yi-hung; Lin, Pei-lin; Hsu, Hui-yu; Wu, Ya-ting; Yang, Han-yin; Lu, Dah-yuu; Huang, Shiang-suo; Hsieh, Ching-liang; Lin, Jaung-geng

    2010-01-01

    Aim: To investigate the effects of 2′-hydroxy-4′-methoxyacetophenone (paeonol) on the electrophysiological behavior of a central neuron (right parietal 4; RP4) of the giant African snail (Achatina fulica Ferussac). Methods: Intracellular recordings and the two-electrode voltage clamp method were used to study the effects of paeonol on the RP4 neuron. Results: The RP4 neuron generated spontaneous action potentials. Bath application of paeonol at a concentration of ≥500 μmol/L reversibly elicited action potential bursts in a concentration-dependent manner. Immersing the neurons in Co2+-substituted Ca2+-free solution did not block paeonol-elicited bursting. Pretreatment with the protein kinase A (PKA) inhibitor KT-5720 or the protein kinase C (PKC) inhibitor Ro 31-8220 did not affect the action potential bursts. Voltage-clamp studies revealed that paeonol at a concentration of 500 μmol/L had no remarkable effects on the total inward currents, whereas paeonol decreased the delayed rectifying K+ current (IKD) and the fast-inactivating K+ current (IA). Application of 4-aminopyridine (4-AP 5 mmol/L), an inhibitor of IA, or charybdotoxin 250 nmol/L, an inhibitor of the Ca2+-activated K+ current (IK(Ca)), failed to elicit action potential bursts, whereas tetraethylammonium chloride (TEA 50 mmol/L), an IKD blocker, successfully elicited action potential bursts. At a lower concentration of 5 mmol/L, TEA facilitated the induction of action potential bursts elicited by paeonol. Conclusion: Paeonol elicited a bursting firing pattern of action potentials in the RP4 neuron and this activity relates closely to the inhibitory effects of paeonol on the IKD. PMID:21042287

  10. [Multi-channel in vivo recording techniques: signal processing of action potentials and local field potentials].

    PubMed

    Xu, Jia-Min; Wang, Ce-Qun; Lin, Long-Nian

    2014-06-25

    Multi-channel in vivo recording techniques are used to record ensemble neuronal activity and local field potentials (LFP) simultaneously. One of the key points for the technique is how to process these two sets of recorded neural signals properly so that data accuracy can be assured. We intend to introduce data processing approaches for action potentials and LFP based on the original data collected through multi-channel recording system. Action potential signals are high-frequency signals, hence high sampling rate of 40 kHz is normally chosen for recording. Based on waveforms of extracellularly recorded action potentials, tetrode technology combining principal component analysis can be used to discriminate neuronal spiking signals from differently spatially distributed neurons, in order to obtain accurate single neuron spiking activity. LFPs are low-frequency signals (lower than 300 Hz), hence the sampling rate of 1 kHz is used for LFPs. Digital filtering is required for LFP analysis to isolate different frequency oscillations including theta oscillation (4-12 Hz), which is dominant in active exploration and rapid-eye-movement (REM) sleep, gamma oscillation (30-80 Hz), which is accompanied by theta oscillation during cognitive processing, and high frequency ripple oscillation (100-250 Hz) in awake immobility and slow wave sleep (SWS) state in rodent hippocampus. For the obtained signals, common data post-processing methods include inter-spike interval analysis, spike auto-correlation analysis, spike cross-correlation analysis, power spectral density analysis, and spectrogram analysis.

  11. Selective activation of heteromeric SK channels contributes to action potential repolarization in mouse atrial myocytes.

    PubMed

    Hancock, Jane M; Weatherall, Kate L; Choisy, Stéphanie C; James, Andrew F; Hancox, Jules C; Marrion, Neil V

    2015-05-01

    Activation of small conductance calcium-activated potassium (SK) channels is proposed to contribute to repolarization of the action potential in atrial myocytes. This role is controversial, as these cardiac SK channels appear to exhibit an uncharacteristic pharmacology. The objectives of this study were to resolve whether activation of SK channels contributes to atrial action potential repolarization and to determine the likely subunit composition of the channel. The effect of 2 SK channel inhibitors was assessed on outward current evoked in voltage clamp and on action potential duration in perforated patch and whole-cell current clamp recording from acutely isolated mouse atrial myocytes. The presence of SK channel subunits was assessed using immunocytochemistry. A significant component of outward current was reduced by the SK channel blockers apamin and UCL1684. Block by apamin displayed a sensitivity indicating that this current was carried by homomeric SK2 channels. Action potential duration was significantly prolonged by UCL1684, but not by apamin. This effect was accompanied by an increase in beat-to-beat variability and action potential triangulation. This pharmacology was matched by that of expressed heteromeric SK2-SK3 channels in HEK293 cells. Immunocytochemistry showed that atrial myocytes express both SK2 and SK3 channels with an overlapping expression pattern. Only proposed heteromeric SK2-SK3 channels are physiologically activated to contribute to action potential repolarization, which is indicated by the difference in pharmacology of evoked outward current and prolongation of atrial action potential duration. The effect of blocking this channel on the action potential suggests that SK channel inhibition during cardiac function has the potential to be proarrhythmic. Copyright © 2015 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

  12. The Effect of Substrate Stiffness on Cardiomyocyte Action Potentials.

    PubMed

    Boothe, Sean D; Myers, Jackson D; Pok, Seokwon; Sun, Junping; Xi, Yutao; Nieto, Raymond M; Cheng, Jie; Jacot, Jeffrey G

    2016-12-01

    The stiffness of myocardial tissue changes significantly at birth and during neonatal development, concurrent with significant changes in contractile and electrical maturation of cardiomyocytes. Previous studies by our group have shown that cardiomyocytes generate maximum contractile force when cultured on a substrate with a stiffness approximating native cardiac tissue. However, effects of substrate stiffness on the electrophysiology and ion currents in cardiomyocytes have not been fully characterized. In this study, neonatal rat ventricular myocytes were cultured on the surface of flat polyacrylamide hydrogels with elastic moduli ranging from 1 to 25 kPa. Using whole-cell patch clamping, action potentials and L-type calcium currents were recorded. Cardiomyocytes cultured on hydrogels with a 9 kPa elastic modulus, similar to that of native myocardium, had the longest action potential duration. Additionally, the voltage at maximum calcium flux significantly decreased in cardiomyocytes on hydrogels with an elastic modulus higher than 9 kPa, and the mean inactivation voltage decreased with increasing stiffness. Interestingly, the expression of the L-type calcium channel subunit α gene and channel localization did not change with stiffness. Substrate stiffness significantly affects action potential length and calcium flux in cultured neonatal rat cardiomyocytes in a manner that may be unrelated to calcium channel expression. These results may explain functional differences in cardiomyocytes resulting from changes in the elastic modulus of the extracellular matrix, as observed during embryonic development, in ischemic regions of the heart after myocardial infarction, and during dilated cardiomyopathy.

  13. Modelling in vivo action potential propagation along a giant axon.

    PubMed

    George, Stuart; Foster, Jamie M; Richardson, Giles

    2015-01-01

    A partial differential equation model for the three-dimensional current flow in an excitable, unmyelinated axon is considered. Where the axon radius is significantly below a critical value R(crit) (that depends upon intra- and extra-cellular conductivity and ion channel conductance) the resistance of the intracellular space is significantly higher than that of the extracellular space, such that the potential outside the axon is uniformly small whilst the intracellular potential is approximated by the transmembrane potential. In turn, since the current flow is predominantly axial, it can be shown that the transmembrane potential is approximated by a solution to the one-dimensional cable equation. It is noted that the radius of the squid giant axon, investigated by (Hodgkin and Huxley 1952e), lies close to R(crit). This motivates us to apply the three-dimensional model to the squid giant axon and compare the results thus found to those obtained using the cable equation. In the context of the in vitro experiments conducted in (Hodgkin and Huxley 1952e) we find only a small difference between the wave profiles determined using these two different approaches and little difference between the speeds of action potential propagation predicted. This suggests that the cable equation approximation is accurate in this scenario. However when applied to the it in vivo setting, in which the conductivity of the surrounding tissue is considerably lower than that of the axoplasm, there are marked differences in both wave profile and speed of action potential propagation calculated using the two approaches. In particular, the cable equation significantly over predicts the increase in the velocity of propagation as axon radius increases. The consequences of these results are discussed in terms of the evolutionary costs associated with increasing the speed of action potential propagation by increasing axon radius.

  14. 7 CFR 1945.19 - Reporting potential natural disasters and initial actions.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 13 2012-01-01 2012-01-01 false Reporting potential natural disasters and initial... Assistance-General § 1945.19 Reporting potential natural disasters and initial actions. (a) Purpose. The purpose of reporting potential natural disasters is to provide a systematic procedure for rapid reporting...

  15. 7 CFR 1945.19 - Reporting potential natural disasters and initial actions.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 13 2011-01-01 2009-01-01 true Reporting potential natural disasters and initial... Assistance-General § 1945.19 Reporting potential natural disasters and initial actions. (a) Purpose. The purpose of reporting potential natural disasters is to provide a systematic procedure for rapid reporting...

  16. 7 CFR 1945.19 - Reporting potential natural disasters and initial actions.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 13 2010-01-01 2009-01-01 true Reporting potential natural disasters and initial... Assistance-General § 1945.19 Reporting potential natural disasters and initial actions. (a) Purpose. The purpose of reporting potential natural disasters is to provide a systematic procedure for rapid reporting...

  17. Consequences of converting graded to action potentials upon neural information coding and energy efficiency.

    PubMed

    Sengupta, Biswa; Laughlin, Simon Barry; Niven, Jeremy Edward

    2014-01-01

    Information is encoded in neural circuits using both graded and action potentials, converting between them within single neurons and successive processing layers. This conversion is accompanied by information loss and a drop in energy efficiency. We investigate the biophysical causes of this loss of information and efficiency by comparing spiking neuron models, containing stochastic voltage-gated Na(+) and K(+) channels, with generator potential and graded potential models lacking voltage-gated Na(+) channels. We identify three causes of information loss in the generator potential that are the by-product of action potential generation: (1) the voltage-gated Na(+) channels necessary for action potential generation increase intrinsic noise and (2) introduce non-linearities, and (3) the finite duration of the action potential creates a 'footprint' in the generator potential that obscures incoming signals. These three processes reduce information rates by ∼50% in generator potentials, to ∼3 times that of spike trains. Both generator potentials and graded potentials consume almost an order of magnitude less energy per second than spike trains. Because of the lower information rates of generator potentials they are substantially less energy efficient than graded potentials. However, both are an order of magnitude more efficient than spike trains due to the higher energy costs and low information content of spikes, emphasizing that there is a two-fold cost of converting analogue to digital; information loss and cost inflation.

  18. Action potentials contribute to epileptic high-frequency oscillations recorded with electrodes remote from neurons.

    PubMed

    Kobayashi, Katsuhiro; Akiyama, Tomoyuki; Ohmori, Iori; Yoshinaga, Harumi; Gotman, Jean

    2015-05-01

    The importance of epileptic high-frequency oscillations (HFOs) in electroencephalogram (EEG) is growing. Action potentials generating some HFOs are observed in the vicinity of neurons in experimental animals. However electrodes that are remote from neurons, as in case of clinical situations, should not record action potentials. We propose to resolve this question by a realistic simulation of epileptic neuronal network. The rat dentate gyrus with sclerosis was simulated in silico. We computed the current dipole moment generated by each granule cell and the field potentials in a measurement area far from neurons. The dentate gyrus was stimulated through synaptic input to evoke discharges resembling interictal epileptiform discharges, which had superimposed HFOs⩽295Hz that were recordable with remote electrodes and represented bursts of action potentials of granule cells. The increase in power of HFOs was associated with the progression of sclerosis, the reduction of GABAergic inhibition, and the increase in cell connectivity. Spectral frequency of HFOs had similar tendencies. HFOs recorded with electrodes remote from neurons could actually be generated by clusters of action potentials. The phenomenon of action potentials recorded with remote electrodes can possibly extend the clinical meaning of EEG. Copyright © 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  19. Neural correlates of action perception at the onset of functional grasping

    PubMed Central

    Daum, Moritz M.; Handl, Andrea; Gredebäck, Gustaf

    2015-01-01

    Event-related potentials were recorded while infants observe congruent or incongruent grasping actions at the age when organized grasping first emerges (4–6 months of age). We demonstrate that the event-related potential component P400 encodes the congruency of power grasps at the age of 6 months (Experiment 1) and in 5-month-old infants that have developed the ability to use power grasps (Experiment 2). This effect does not extend to precision grasps, which infants cannot perform (Experiment 3). Our findings suggest that infants’ encoding of the relationship between an object and a grasping hand (the action–perception link) is highly specialized to actions and manual configurations of actions that infants are able to perform. PMID:25193947

  20. Influence of asymmetric attenuation of single and paired dendritic inputs on summation of synaptic potentials and initiation of action potentials.

    PubMed

    Fortier, Pierre A; Bray, Chelsea

    2013-04-16

    Previous studies revealed mechanisms of dendritic inputs leading to action potential initiation at the axon initial segment and backpropagation into the dendritic tree. This interest has recently expanded toward the communication between different parts of the dendritic tree which could preprocess information before reaching the soma. This study tested for effects of asymmetric voltage attenuation between different sites in the dendritic tree on summation of synaptic inputs and action potential initiation using the NEURON simulation environment. Passive responses due to the electrical equivalent circuit of the three-dimensional neuron architecture with leak channels were examined first, followed by the responses after adding voltage-gated channels and finally synaptic noise. Asymmetric attenuation of voltage, which is a function of asymmetric input resistance, was seen between all pairs of dendritic sites but the transfer voltages (voltage recorded at the opposite site from stimulation among a pair of dendritic sites) were equal and also summed linearly with local voltage responses during simultaneous stimulation of both sites. In neurons with voltage-gated channels, we reproduced the observations where a brief stimulus to the proximal ascending dendritic branch of a pyramidal cell triggers a local action potential but a long stimulus triggers a somal action potential. Combined stimulation of a pair of sites in this proximal dendrite did not alter this pattern. The attraction of the action potential onset toward the soma with a long stimulus in the absence of noise was due to the higher density of voltage-gated sodium channels at the axon initial segment. This attraction was, however, negligible at the most remote distal dendritic sites and was replaced by an effect due to high input resistance. Action potential onset occurred at the dendritic site of higher input resistance among a pair of remote dendritic sites, irrespective of which of these two sites received

  1. Understanding the Electrical Behavior of the Action Potential in Terms of Elementary Electrical Sources

    ERIC Educational Resources Information Center

    Rodriguez-Falces, Javier

    2015-01-01

    A concept of major importance in human electrophysiology studies is the process by which activation of an excitable cell results in a rapid rise and fall of the electrical membrane potential, the so-called action potential. Hodgkin and Huxley proposed a model to explain the ionic mechanisms underlying the formation of action potentials. However,…

  2. Action potential-independent and pharmacologically unique vesicular serotonin release from dendrites

    PubMed Central

    Colgan, Lesley A.; Cavolo, Samantha L.; Commons, Kathryn G.; Levitan, Edwin S.

    2012-01-01

    Serotonin released within the dorsal raphe nucleus (DR) induces feedback inhibition of serotonin neuron activity and consequently regulates mood-controlling serotonin release throughout the forebrain. Serotonin packaged in vesicles is released in response to action potentials by the serotonin neuron soma and terminals, but the potential for release by dendrites is unknown. Here three-photon (3P) microscopy imaging of endogenous serotonin in living rat brain slice, immunofluorescence and immuno-gold electron microscopy detection of VMAT2 (vesicular monoamine transporter 2) establish the presence of vesicular serotonin within DR dendrites. Furthermore, activation of glutamate receptors is shown to induce vesicular serotonin release from dendrites. However, unlike release from the soma and terminals, dendritic serotonin release is independent of action potentials, relies on L-type Ca2+ channels, is induced preferentially by NMDA, and displays distinct sensitivity to the selective serotonin reuptake inhibitor (SSRI) antidepressant fluoxetine. The unique control of dendritic serotonin release has important implications for DR physiology and the antidepressant action of SSRIs, dihydropyridines and NMDA receptor antagonists. PMID:23136413

  3. Collision of two action potentials in a single excitable cell.

    PubMed

    Fillafer, Christian; Paeger, Anne; Schneider, Matthias F

    2017-12-01

    It is a common incident in nature, that two waves or pulses run into each other head-on. The outcome of such an event is of special interest, because it allows conclusions about the underlying physical nature of the pulses. The present experimental study dealt with the head-on meeting of two action potentials (AP) in a single excitable plant cell (Chara braunii internode). The membrane potential was monitored with multiple sensors along a single excitable cell. In control experiments, an AP was excited electrically at either end of the cell cylinder. Subsequently, stimuli were applied simultaneously at both ends of the cell in order to generate two APs that met each other head-on. When two action potentials propagated into each other, the pulses did not penetrate but annihilated (N=26 experiments in n=10 cells). APs in excitable plant cells did not penetrate upon meeting head-on. In the classical electrical model, this behavior is specifically attributed to relaxation of ion channel proteins. From an acoustic point of view, annihilation can be viewed as a result of nonlinear material properties (e.g. a phase change). The present results suggest that APs in excitable animal and plant cells belong to a similar class of nonlinear phenomena. Intriguingly, other excitation waves in biology (intracellular waves, cortical spreading depression, etc.) also annihilate upon collision and are thus expected to follow the same underlying principles as the observed action potentials. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Tank waste remediation system configuration management plan

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Vann, J.M.

    The configuration management program for the Tank Waste Remediation System (TWRS) Project Mission supports management of the project baseline by providing the mechanisms to identify, document, and control the functional and physical characteristics of the products. This document is one of the tools used to develop and control the mission and work. It is an integrated approach for control of technical, cost, schedule, and administrative information necessary to manage the configurations for the TWRS Project Mission. Configuration management focuses on five principal activities: configuration management system management, configuration identification, configuration status accounting, change control, and configuration management assessments. TWRS Projectmore » personnel must execute work in a controlled fashion. Work must be performed by verbatim use of authorized and released technical information and documentation. Application of configuration management will be consistently applied across all TWRS Project activities and assessed accordingly. The Project Hanford Management Contract (PHMC) configuration management requirements are prescribed in HNF-MP-013, Configuration Management Plan (FDH 1997a). This TWRS Configuration Management Plan (CMP) implements those requirements and supersedes the Tank Waste Remediation System Configuration Management Program Plan described in Vann, 1996. HNF-SD-WM-CM-014, Tank Waste Remediation System Configuration Management Implementation Plan (Vann, 1997) will be revised to implement the requirements of this plan. This plan provides the responsibilities, actions and tools necessary to implement the requirements as defined in the above referenced documents.« less

  5. The monophasic action potential upstroke: a means of characterizing local conduction.

    PubMed

    Levine, J H; Moore, E N; Kadish, A H; Guarnieri, T; Spear, J F

    1986-11-01

    The upstrokes of monophasic action potentials (MAPs) recorded with an extracellular pressure electrode were characterized in isolated canine tissue preparations in vitro. The characteristics of the MAP upstroke were compared with those of the local action potential foot as well as with the characteristics of approaching electrical activation during uniform and asynchronous conduction. The upstroke of the MAP was exponential during uniform conduction. The time constant of rise of the MAP upstroke (TMAP) correlated with that of the action potential foot (Tfoot): TMAP + 1.01 Tfoot + 0.50; r2 = .80. Furthermore, changes in Tfoot with alterations in cycle length were associated with similar changes in TMAP: Tfoot = 1.06 TMAP - 0.11; r2 = .78. In addition, TMAP and Tfoot both deviated from exponential during asynchronous activation; the inflections that developed in the MAP upstroke correlated in time with intracellular action potential upstrokes that were asynchronous in onset in these tissues. Finally, the field of view of the MAP was determined and was found to be dependent in part on tissue architecture and the space constant. Specifically, the field of view of the MAP was found to be greater parallel compared with transverse to fiber orientation (6.02 +/- 1.74 vs 3.03 +/- 1.10 mm; p less than .01). These data suggest that the MAP upstroke may be used to define and characterize local electrical activation. The relatively large field of view of the MAP suggests that this technique may be a sensitive means to record focal membrane phenomena in vivo.

  6. Consequences of Converting Graded to Action Potentials upon Neural Information Coding and Energy Efficiency

    PubMed Central

    Sengupta, Biswa; Laughlin, Simon Barry; Niven, Jeremy Edward

    2014-01-01

    Information is encoded in neural circuits using both graded and action potentials, converting between them within single neurons and successive processing layers. This conversion is accompanied by information loss and a drop in energy efficiency. We investigate the biophysical causes of this loss of information and efficiency by comparing spiking neuron models, containing stochastic voltage-gated Na+ and K+ channels, with generator potential and graded potential models lacking voltage-gated Na+ channels. We identify three causes of information loss in the generator potential that are the by-product of action potential generation: (1) the voltage-gated Na+ channels necessary for action potential generation increase intrinsic noise and (2) introduce non-linearities, and (3) the finite duration of the action potential creates a ‘footprint’ in the generator potential that obscures incoming signals. These three processes reduce information rates by ∼50% in generator potentials, to ∼3 times that of spike trains. Both generator potentials and graded potentials consume almost an order of magnitude less energy per second than spike trains. Because of the lower information rates of generator potentials they are substantially less energy efficient than graded potentials. However, both are an order of magnitude more efficient than spike trains due to the higher energy costs and low information content of spikes, emphasizing that there is a two-fold cost of converting analogue to digital; information loss and cost inflation. PMID:24465197

  7. Calcium-Induced calcium release during action potential firing in developing inner hair cells.

    PubMed

    Iosub, Radu; Avitabile, Daniele; Grant, Lisa; Tsaneva-Atanasova, Krasimira; Kennedy, Helen J

    2015-03-10

    In the mature auditory system, inner hair cells (IHCs) convert sound-induced vibrations into electrical signals that are relayed to the central nervous system via auditory afferents. Before the cochlea can respond to normal sound levels, developing IHCs fire calcium-based action potentials that disappear close to the onset of hearing. Action potential firing triggers transmitter release from the immature IHC that in turn generates experience-independent firing in auditory neurons. These early signaling events are thought to be essential for the organization and development of the auditory system and hair cells. A critical component of the action potential is the rise in intracellular calcium that activates both small conductance potassium channels essential during membrane repolarization, and triggers transmitter release from the cell. Whether this calcium signal is generated by calcium influx or requires calcium-induced calcium release (CICR) is not yet known. IHCs can generate CICR, but to date its physiological role has remained unclear. Here, we used high and low concentrations of ryanodine to block or enhance CICR to determine whether calcium release from intracellular stores affected action potential waveform, interspike interval, or changes in membrane capacitance during development of mouse IHCs. Blocking CICR resulted in mixed action potential waveforms with both brief and prolonged oscillations in membrane potential and intracellular calcium. This mixed behavior is captured well by our mathematical model of IHC electrical activity. We perform two-parameter bifurcation analysis of the model that predicts the dependence of IHCs firing patterns on the level of activation of two parameters, the SK2 channels activation and CICR rate. Our data show that CICR forms an important component of the calcium signal that shapes action potentials and regulates firing patterns, but is not involved directly in triggering exocytosis. These data provide important insights

  8. Somatic spikes regulate dendritic signaling in small neurons in the absence of backpropagating action potentials.

    PubMed

    Myoga, Michael H; Beierlein, Michael; Regehr, Wade G

    2009-06-17

    Somatic spiking is known to regulate dendritic signaling and associative synaptic plasticity in many types of large neurons, but it is unclear whether somatic action potentials play similar roles in small neurons. Here we ask whether somatic action potentials can also influence dendritic signaling in an electrically compact neuron, the cerebellar stellate cell (SC). Experiments were conducted in rat brain slices using a combination of imaging and electrophysiology. We find that somatic action potentials elevate dendritic calcium levels in SCs. There was little attenuation of calcium signals with distance from the soma in SCs from postnatal day 17 (P17)-P19 rats, which had dendrites that averaged 60 microm in length, and in short SC dendrites from P30-P33 rats. Somatic action potentials evoke dendritic calcium increases that are not affected by blocking dendritic sodium channels. This indicates that dendritic signals in SCs do not rely on dendritic sodium channels, which differs from many types of large neurons, in which dendritic sodium channels and backpropagating action potentials allow somatic spikes to control dendritic calcium signaling. Despite the lack of active backpropagating action potentials, we find that trains of somatic action potentials elevate dendritic calcium sufficiently to release endocannabinoids and retrogradely suppress parallel fiber to SC synapses in P17-P19 rats. Prolonged SC firing at physiologically realistic frequencies produces retrograde suppression when combined with low-level group I metabotropic glutamate receptor activation. Somatic spiking also interacts with synaptic stimulation to promote associative plasticity. These findings indicate that in small neurons the passive spread of potential within dendrites can allow somatic spiking to regulate dendritic calcium signaling and synaptic plasticity.

  9. A device for emulating cuff recordings of action potentials propagating along peripheral nerves.

    PubMed

    Rieger, Robert; Schuettler, Martin; Chuang, Sheng-Chih

    2014-09-01

    This paper describes a device that emulates propagation of action potentials along a peripheral nerve, suitable for reproducible testing of bio-potential recording systems using nerve cuff electrodes. The system is a microcontroller-based stand-alone instrument which uses established nerve and electrode models to represent neural activity of real nerves recorded with a nerve cuff interface, taking into consideration electrode impedance, voltages picked up by the electrodes, and action potential propagation characteristics. The system emulates different scenarios including compound action potentials with selectable propagation velocities and naturally occurring nerve traffic from different velocity fiber populations. Measured results from a prototype implementation are reported and compared with in vitro recordings from Xenopus Laevis frog sciatic nerve, demonstrating that the electrophysiological setting is represented to a satisfactory degree, useful for the development, optimization and characterization of future recording systems.

  10. Examination of a demyelinated fiber by action-potential-encoded second harmonic generation

    NASA Astrophysics Data System (ADS)

    Chen, Xin-guang; Luo, Zhi-hui; Yang, Hong-qin; Huang, Yi-mei; Xie, Shu-sen

    2012-03-01

    Axonal demyelination is a common phenomenon in the nervous system in human. Conventional measured approaches such as surface recording electrode and diffusion tensor imaging, are hard to fast and accurately determine the demyelinated status of a fiber. In this study, we first presented a mathematical model of nerve fiber demyelination, and it was combined with second harmonic generation(SHG) technique to study the characteristics of action-potential-encoded SHG and analyze the sensitivity of SHG signals responded to membrane potential. And then, we used this approach to fast examine the injured myelin sheaths resulted from demyelination. Each myelin sheath of a fiber was examined simultaneously by this approach. The results showed that fiber demyelination led to observable attenuation of action potential amplitude. The delay of action potential conduction would be markedly observed when the fiber demyelination was more than 80%. Furthermore, the normal and injured myelin sheaths of a myelinated fiber could be distinguished via the changes of SHG signals, which revealed the possibility of SHG technique in the examination of a demyelinated fiber. Our study shows that this approach may have potential application values in clinic.

  11. Fully unsteady subsonic and supersonic potential aerodynamics for complex aircraft configurations for flutter applications

    NASA Technical Reports Server (NTRS)

    Tseng, K.; Morino, L.

    1975-01-01

    A general theory for study, oscillatory or fully unsteady potential compressible aerodynamics around complex configurations is presented. Using the finite-element method to discretize the space problem, one obtains a set of differential-delay equations in time relating the potential to its normal derivative which is expressed in terms of the generalized coordinates of the structure. For oscillatory flow, the motion consists of sinusoidal oscillations around a steady, subsonic or supersonic flow. For fully unsteady flow, the motion is assumed to consist of constant subsonic or supersonic speed for time t or = 0 and of small perturbations around the steady state for time t 0.

  12. Configurational entropy: an improvement of the quasiharmonic approximation using configurational temperature.

    PubMed

    Nguyen, Phuong H; Derreumaux, Philippe

    2012-01-14

    One challenge in computational biophysics and biology is to develop methodologies able to estimate accurately the configurational entropy of macromolecules. Among many methods, the quasiharmonic approximation (QH) is most widely used as it is simple in both theory and implementation. However, it has been shown that this method becomes inaccurate by overestimating entropy for systems with rugged free energy landscapes. Here, we propose a simple method to improve the QH approximation, i.e., to reduce QH entropy. We approximate the potential energy landscape of the system by an effective harmonic potential, and request that this potential must produce exactly the configurational temperature of the system. Due to this constraint, the force constants associated with the effective harmonic potential are increased, or equivalently, entropy of motion governed by this effective harmonic potential is reduced. We also introduce the effective configurational temperature concept which can be used as an indicator to check the anharmonicity of the free energy landscape. To validate the new method we compare it with the recently developed expansion approximate method by calculating entropy of one simple model system and two peptides with 3 and 16 amino acids either in gas phase or in explicit solvent. We show that the new method appears to be a good choice in practice as it is a compromise between accuracy and computational speed. A modification of the expansion approximate method is also introduced and advantages are discussed in some detail.

  13. Naturalistic stimulation changes the dynamic response of action potential encoding in a mechanoreceptor

    PubMed Central

    Pfeiffer, Keram; French, Andrew S.

    2015-01-01

    Naturalistic signals were created from vibrations made by locusts walking on a Sansevieria plant. Both naturalistic and Gaussian noise signals were used to mechanically stimulate VS-3 slit-sense mechanoreceptor neurons of the spider, Cupiennius salei, with stimulus amplitudes adjusted to give similar firing rates for either stimulus. Intracellular microelectrodes recorded action potentials, receptor potential, and receptor current, using current clamp and voltage clamp. Frequency response analysis showed that naturalistic stimulation contained relatively more power at low frequencies, and caused increased neuronal sensitivity to higher frequencies. In contrast, varying the amplitude of Gaussian stimulation did not change neuronal dynamics. Naturalistic stimulation contained less entropy than Gaussian, but signal entropy was higher than stimulus in the resultant receptor current, indicating addition of uncorrelated noise during transduction. The presence of added noise was supported by measuring linear information capacity in the receptor current. Total entropy and information capacity in action potentials produced by either stimulus were much lower than in earlier stages, and limited to the maximum entropy of binary signals. We conclude that the dynamics of action potential encoding in VS-3 neurons are sensitive to the form of stimulation, but entropy and information capacity of action potentials are limited by firing rate. PMID:26578975

  14. Flexible graphene transistors for recording cell action potentials

    NASA Astrophysics Data System (ADS)

    Blaschke, Benno M.; Lottner, Martin; Drieschner, Simon; Bonaccini Calia, Andrea; Stoiber, Karolina; Rousseau, Lionel; Lissourges, Gaëlle; Garrido, Jose A.

    2016-06-01

    Graphene solution-gated field-effect transistors (SGFETs) are a promising platform for the recording of cell action potentials due to the intrinsic high signal amplification of graphene transistors. In addition, graphene technology fulfills important key requirements for in-vivo applications, such as biocompability, mechanical flexibility, as well as ease of high density integration. In this paper we demonstrate the fabrication of flexible arrays of graphene SGFETs on polyimide, a biocompatible polymeric substrate. We investigate the transistor’s transconductance and intrinsic electronic noise which are key parameters for the device sensitivity, confirming that the obtained values are comparable to those of rigid graphene SGFETs. Furthermore, we show that the devices do not degrade during repeated bending and the transconductance, governed by the electronic properties of graphene, is unaffected by bending. After cell culture, we demonstrate the recording of cell action potentials from cardiomyocyte-like cells with a high signal-to-noise ratio that is higher or comparable to competing state of the art technologies. Our results highlight the great capabilities of flexible graphene SGFETs in bioelectronics, providing a solid foundation for in-vivo experiments and, eventually, for graphene-based neuroprosthetics.

  15. Correlation of intercalation potential with d-electron configurations for cathode compounds of lithium-ion batteries.

    PubMed

    Chen, Zhenlian; Zhang, Caixia; Zhang, Zhiyong; Li, Jun

    2014-07-14

    The d-electron localization is widely recognized as important to transport properties of transition metal compounds, but its role in the energy conversion of intercalation reactions of cathode compounds is still not fully explored. In this work, the correlation of intercalation potential with electron affinity, a key energy term controlling electron intercalation, then with d-electron configuration, is investigated. Firstly, we find that the change of the intercalation potential with respect to the transition metal cations within the same structure class is correlated in an approximately mirror relationship with the electron affinity, based on first-principles calculations on three typical categories of cathode compounds including layered oxides and polyoxyanions Then, by using a new model Hamiltonian based on the crystal-field theory, we reveal that the evolution is governed by the combination of the crystal-field splitting and the on-site d-d exchange interactions. Further, we show that the charge order in solid-solution composites and the compatibility of multi-electron redox steps could be inferred from the energy terms with the d-electron configuration alternations. These findings may be applied to rationally designing new chemistry for the lithium-ion batteries and other metal-ion batteries.

  16. Rate dependency of delayed rectifier currents during the guinea-pig ventricular action potential

    PubMed Central

    Rocchetti, Marcella; Besana, Alessandra; Gurrola, Georgina B; Possani, Lourival D; Zaza, Antonio

    2001-01-01

    The action potential clamp technique was exploited to evaluate the rate dependency of delayed rectifier currents (IKr and IKs) during physiological electrical activity. IKr and IKs were measured in guinea-pig ventricular myocytes at pacing cycle lengths (CL) of 1000 and 250 ms.A shorter CL, with the attendant changes in action potential shape, was associated with earlier activation and increased magnitude of both IKr and IKs. Nonetheless, the relative contributions of IKr and IKs to total transmembrane current were independent of CL.Shortening of diastolic interval only (constant action potential shape) enhanced IKs, but not IKr.IKr was increased by a change in the action potential shape only (constant diastolic interval).In ramp clamp experiments, IKr amplitude was directly proportional to repolarization rate at values within the low physiological range (< 1.0 V s−1); at higher repolarization rates proportionality became shallower and finally reversed.When action potential duration (APD) was modulated by constant current injection (I-clamp), repolarization rates > 1.0 V s−1 were associated with a reduced effect of IKr block on APD. The effect of changes in repolarization rate was independent of CL and occurred in the presence of IKs blockade.In spite of its complexity, the behaviour of IKr was accurately predicted by a numerical model based entirely on known kinetic properties of the current.Both IKr and IKs may be increased at fast heart rates, but this may occur through completely different mechanisms. The mechanisms identified are such as to contribute to abnormal rate dependency of repolarization in prolonged repolarization syndromes. PMID:11483703

  17. Restitution slope is principally determined by steady-state action potential duration.

    PubMed

    Shattock, Michael J; Park, Kyung Chan; Yang, Hsiang-Yu; Lee, Angela W C; Niederer, Steven; MacLeod, Kenneth T; Winter, James

    2017-06-01

    The steepness of the action potential duration (APD) restitution curve and local tissue refractoriness are both thought to play important roles in arrhythmogenesis. Despite this, there has been little recognition of the apparent association between steady-state APD and the slope of the restitution curve. The objective of this study was to test the hypothesis that restitution slope is determined by APD and to examine the relationship between restitution slope, refractoriness and susceptibility to VF. Experiments were conducted in isolated hearts and ventricular myocytes from adult guinea pigs and rabbits. Restitution curves were measured under control conditions and following intervention to prolong (clofilium, veratridine, bretylium, low [Ca]e, chronic transverse aortic constriction) or shorten (catecholamines, rapid pacing) ventricular APD. Despite markedly differing mechanisms of action, all interventions that prolonged the action potential led to a steepening of the restitution curve (and vice versa). Normalizing the restitution curve as a % of steady-state APD abolished the difference in restitution curves with all interventions. Effects on restitution were preserved when APD was modulated by current injection in myocytes pre-treated with the calcium chelator BAPTA-AM - to abolish the intracellular calcium transient. The non-linear relation between APD and the rate of repolarization of the action potential is shown to underpin the common influence of APD on the slope of the restitution curve. Susceptibility to VF was found to parallel changes in APD/refractoriness, rather than restitution slope. Steady-state APD is the principal determinant of the slope of the ventricular electrical restitution curve. In the absence of post-repolarization refractoriness, factors that prolong the action potential would be expected to steepen the restitution curve. However, concomitant changes in tissue refractoriness act to reduce susceptibility to sustained VF. Dependence on

  18. Restitution slope is principally determined by steady-state action potential duration

    PubMed Central

    Shattock, Michael J.; Park, Kyung Chan; Yang, Hsiang-Yu; Lee, Angela W. C.; Niederer, Steven; MacLeod, Kenneth T.

    2017-01-01

    Aims The steepness of the action potential duration (APD) restitution curve and local tissue refractoriness are both thought to play important roles in arrhythmogenesis. Despite this, there has been little recognition of the apparent association between steady-state APD and the slope of the restitution curve. The objective of this study was to test the hypothesis that restitution slope is determined by APD and to examine the relationship between restitution slope, refractoriness and susceptibility to VF. Methods and results Experiments were conducted in isolated hearts and ventricular myocytes from adult guinea pigs and rabbits. Restitution curves were measured under control conditions and following intervention to prolong (clofilium, veratridine, bretylium, low [Ca]e, chronic transverse aortic constriction) or shorten (catecholamines, rapid pacing) ventricular APD. Despite markedly differing mechanisms of action, all interventions that prolonged the action potential led to a steepening of the restitution curve (and vice versa). Normalizing the restitution curve as a % of steady-state APD abolished the difference in restitution curves with all interventions. Effects on restitution were preserved when APD was modulated by current injection in myocytes pre-treated with the calcium chelator BAPTA-AM – to abolish the intracellular calcium transient. The non-linear relation between APD and the rate of repolarization of the action potential is shown to underpin the common influence of APD on the slope of the restitution curve. Susceptibility to VF was found to parallel changes in APD/refractoriness, rather than restitution slope. Conclusion(s) Steady-state APD is the principal determinant of the slope of the ventricular electrical restitution curve. In the absence of post-repolarization refractoriness, factors that prolong the action potential would be expected to steepen the restitution curve. However, concomitant changes in tissue refractoriness act to reduce

  19. NeuroGrid: recording action potentials from the surface of the brain.

    PubMed

    Khodagholy, Dion; Gelinas, Jennifer N; Thesen, Thomas; Doyle, Werner; Devinsky, Orrin; Malliaras, George G; Buzsáki, György

    2015-02-01

    Recording from neural networks at the resolution of action potentials is critical for understanding how information is processed in the brain. Here, we address this challenge by developing an organic material-based, ultraconformable, biocompatible and scalable neural interface array (the 'NeuroGrid') that can record both local field potentials(LFPs) and action potentials from superficial cortical neurons without penetrating the brain surface. Spikes with features of interneurons and pyramidal cells were simultaneously acquired by multiple neighboring electrodes of the NeuroGrid, allowing for the isolation of putative single neurons in rats. Spiking activity demonstrated consistent phase modulation by ongoing brain oscillations and was stable in recordings exceeding 1 week's duration. We also recorded LFP-modulated spiking activity intraoperatively in patients undergoing epilepsy surgery. The NeuroGrid constitutes an effective method for large-scale, stable recording of neuronal spikes in concert with local population synaptic activity, enhancing comprehension of neural processes across spatiotemporal scales and potentially facilitating diagnosis and therapy for brain disorders.

  20. Position-dependent patterning of spontaneous action potentials in immature cochlear inner hair cells

    PubMed Central

    Johnson, Stuart L.; Eckrich, Tobias; Kuhn, Stephanie; Zampini, Valeria; Franz, Christoph; Ranatunga, Kishani M.; Roberts, Terri P.; Masetto, Sergio; Knipper, Marlies; Kros, Corné J.; Marcotti, Walter

    2011-01-01

    Spontaneous action potential activity is crucial for mammalian sensory system development. In the auditory system, patterned firing activity has been observed in immature spiral ganglion cells and brain-stem neurons and is likely to depend on cochlear inner hair cell (IHC) action potentials. It remains uncertain whether spiking activity is intrinsic to developing IHCs and whether it shows patterning. We found that action potentials are intrinsically generated by immature IHCs of altricial rodents and that apical IHCs exhibit bursting activity as opposed to more sustained firing in basal cells. We show that the efferent neurotransmitter ACh, by fine-tuning the IHC’s resting membrane potential (Vm), is crucial for the bursting pattern in apical cells. Endogenous extracellular ATP also contributes to the Vm of apical and basal IHCs by activating SK2 channels. We hypothesize that the difference in firing pattern along the cochlea instructs the tonotopic differentiation of IHCs and auditory pathway. PMID:21572434

  1. Position-dependent patterning of spontaneous action potentials in immature cochlear inner hair cells.

    PubMed

    Johnson, Stuart L; Eckrich, Tobias; Kuhn, Stephanie; Zampini, Valeria; Franz, Christoph; Ranatunga, Kishani M; Roberts, Terri P; Masetto, Sergio; Knipper, Marlies; Kros, Corné J; Marcotti, Walter

    2011-06-01

    Spontaneous action potential activity is crucial for mammalian sensory system development. In the auditory system, patterned firing activity has been observed in immature spiral ganglion and brain-stem neurons and is likely to depend on cochlear inner hair cell (IHC) action potentials. It remains uncertain whether spiking activity is intrinsic to developing IHCs and whether it shows patterning. We found that action potentials were intrinsically generated by immature IHCs of altricial rodents and that apical IHCs showed bursting activity as opposed to more sustained firing in basal cells. We show that the efferent neurotransmitter acetylcholine fine-tunes the IHC's resting membrane potential (V(m)), and as such is crucial for the bursting pattern in apical cells. Endogenous extracellular ATP also contributes to the V(m) of apical and basal IHCs by triggering small-conductance Ca(2+)-activated K(+) (SK2) channels. We propose that the difference in firing pattern along the cochlea instructs the tonotopic differentiation of IHCs and auditory pathway.

  2. Effects of acetylcholine and noradrenalin on action potentials of isolated rabbit sinoatrial and atrial myocytes.

    PubMed

    Verkerk, Arie O; Geuzebroek, Guillaume S C; Veldkamp, Marieke W; Wilders, Ronald

    2012-01-01

    The autonomic nervous system controls heart rate and contractility through sympathetic and parasympathetic inputs to the cardiac tissue, with acetylcholine (ACh) and noradrenalin (NA) as the chemical transmitters. In recent years, it has become clear that specific Regulators of G protein Signaling proteins (RGS proteins) suppress muscarinic sensitivity and parasympathetic tone, identifying RGS proteins as intriguing potential therapeutic targets. In the present study, we have identified the effects of 1 μM ACh and 1 μM NA on the intrinsic action potentials of sinoatrial (SA) nodal and atrial myocytes. Single cells were enzymatically isolated from the SA node or from the left atrium of rabbit hearts. Action potentials were recorded using the amphotericin-perforated patch-clamp technique in the absence and presence of ACh, NA, or a combination of both. In SA nodal myocytes, ACh increased cycle length and decreased diastolic depolarization rate, whereas NA decreased cycle length and increased diastolic depolarization rate. Both ACh and NA increased maximum upstroke velocity. Furthermore, ACh hyperpolarized the maximum diastolic potential. In atrial myocytes stimulated at 2 Hz, both ACh and NA hyperpolarized the maximum diastolic potential, increased the action potential amplitude, and increased the maximum upstroke velocity. Action potential duration at 50 and 90% repolarization was decreased by ACh, but increased by NA. The effects of both ACh and NA on action potential duration showed a dose dependence in the range of 1-1000 nM, while a clear-cut frequency dependence in the range of 1-4 Hz was absent. Intermediate results were obtained in the combined presence of ACh and NA in both SA nodal and atrial myocytes. Our data uncover the extent to which SA nodal and atrial action potentials are intrinsically dependent on ACh, NA, or a combination of both and may thus guide further experiments with RGS proteins.

  3. Effects of Acetylcholine and Noradrenalin on Action Potentials of Isolated Rabbit Sinoatrial and Atrial Myocytes

    PubMed Central

    Verkerk, Arie O.; Geuzebroek, Guillaume S. C.; Veldkamp, Marieke W.; Wilders, Ronald

    2012-01-01

    The autonomic nervous system controls heart rate and contractility through sympathetic and parasympathetic inputs to the cardiac tissue, with acetylcholine (ACh) and noradrenalin (NA) as the chemical transmitters. In recent years, it has become clear that specific Regulators of G protein Signaling proteins (RGS proteins) suppress muscarinic sensitivity and parasympathetic tone, identifying RGS proteins as intriguing potential therapeutic targets. In the present study, we have identified the effects of 1 μM ACh and 1 μM NA on the intrinsic action potentials of sinoatrial (SA) nodal and atrial myocytes. Single cells were enzymatically isolated from the SA node or from the left atrium of rabbit hearts. Action potentials were recorded using the amphotericin-perforated patch-clamp technique in the absence and presence of ACh, NA, or a combination of both. In SA nodal myocytes, ACh increased cycle length and decreased diastolic depolarization rate, whereas NA decreased cycle length and increased diastolic depolarization rate. Both ACh and NA increased maximum upstroke velocity. Furthermore, ACh hyperpolarized the maximum diastolic potential. In atrial myocytes stimulated at 2 Hz, both ACh and NA hyperpolarized the maximum diastolic potential, increased the action potential amplitude, and increased the maximum upstroke velocity. Action potential duration at 50 and 90% repolarization was decreased by ACh, but increased by NA. The effects of both ACh and NA on action potential duration showed a dose dependence in the range of 1–1000 nM, while a clear-cut frequency dependence in the range of 1–4 Hz was absent. Intermediate results were obtained in the combined presence of ACh and NA in both SA nodal and atrial myocytes. Our data uncover the extent to which SA nodal and atrial action potentials are intrinsically dependent on ACh, NA, or a combination of both and may thus guide further experiments with RGS proteins. PMID:22754533

  4. Typical gray matter axons in mammalian brain fail to conduct action potentials faithfully at fever-like temperatures.

    PubMed

    Pekala, Dobromila; Szkudlarek, Hanna; Raastad, Morten

    2016-10-01

    We studied the ability of typical unmyelinated cortical axons to conduct action potentials at fever-like temperatures because fever often gives CNS symptoms. We investigated such axons in cerebellar and hippocampal slices from 10 to 25 days old rats at temperatures between 30 and 43°C. By recording with two electrodes along axonal pathways, we confirmed that the axons were able to initiate action potentials, but at temperatures >39°C, the propagation of the action potentials to a more distal recording site was reduced. This temperature-sensitive conduction may be specific for the very thin unmyelinated axons because similar recordings from myelinated CNS axons did not show conduction failures. We found that the conduction fidelity improved with 1 mmol/L TEA in the bath, probably due to block of voltage-sensitive potassium channels responsible for the fast repolarization of action potentials. Furthermore, by recording electrically activated antidromic action potentials from the soma of cerebellar granule cells, we showed that the axons failed less if they were triggered 10-30 msec after another action potential. This was because individual action potentials were followed by a depolarizing after-potential, of constant amplitude and shape, which facilitated conduction of the following action potentials. The temperature-sensitive conduction failures above, but not below, normal body temperature, and the failure-reducing effect of the spike's depolarizing after-potential, are two intrinsic mechanisms in normal gray matter axons that may help us understand how the hyperthermic brain functions. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

  5. ACTION-SPACE CLUSTERING OF TIDAL STREAMS TO INFER THE GALACTIC POTENTIAL

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Sanderson, Robyn E.; Helmi, Amina; Hogg, David W., E-mail: robyn@astro.columbia.edu

    2015-03-10

    We present a new method for constraining the Milky Way halo gravitational potential by simultaneously fitting multiple tidal streams. This method requires three-dimensional positions and velocities for all stars to be fit, but does not require identification of any specific stream or determination of stream membership for any star. We exploit the principle that the action distribution of stream stars is most clustered when the potential used to calculate the actions is closest to the true potential. Clustering is quantified with the Kullback-Leibler Divergence (KLD), which also provides conditional uncertainties for our parameter estimates. We show, for toy Gaia-like datamore » in a spherical isochrone potential, that maximizing the KLD of the action distribution relative to a smoother distribution recovers the input potential. The precision depends on the observational errors and number of streams; using K III giants as tracers, we measure the enclosed mass at the average radius of the sample stars accurate to 3% and precise to 20%-40%. Recovery of the scale radius is precise to 25%, biased 50% high by the small galactocentric distance range of stars in our mock sample (1-25 kpc, or about three scale radii, with mean 6.5 kpc). 20-25 streams with at least 100 stars each are required for a stable confidence interval. With radial velocities (RVs) to 100 kpc, all parameters are determined with ∼10% accuracy and 20% precision (1.3% accuracy for the enclosed mass), underlining the need to complete the RV catalog for faint halo stars observed by Gaia.« less

  6. Click- and chirp-evoked human compound action potentials

    PubMed Central

    Chertoff, Mark; Lichtenhan, Jeffery; Willis, Marie

    2010-01-01

    In the experiments reported here, the amplitude and the latency of human compound action potentials (CAPs) evoked from a chirp stimulus are compared to those evoked from a traditional click stimulus. The chirp stimulus was created with a frequency sweep to compensate for basilar membrane traveling wave delay using the O-Chirp equations from Fobel and Dau [(2004). J. Acoust. Soc. Am. 116, 2213–2222] derived from otoacoustic emission data. Human cochlear traveling wave delay estimates were obtained from derived compound band action potentials provided by Eggermont [(1979). J. Acoust. Soc. Am. 65, 463–470]. CAPs were recorded from an electrode placed on the tympanic membrane (TM), and the acoustic signals were monitored with a probe tube microphone attached to the TM electrode. Results showed that the amplitude and latency of chirp-evoked N1 of the CAP differed from click-evoked CAPs in several regards. For the chirp-evoked CAP, the N1 amplitude was significantly larger than the click-evoked N1s. The latency-intensity function was significantly shallower for chirp-evoked CAPs as compared to click-evoked CAPs. This suggests that auditory nerve fibers respond with more unison to a chirp stimulus than to a click stimulus. PMID:21117748

  7. Action Potential Dynamics in Fine Axons Probed with an Axonally Targeted Optical Voltage Sensor.

    PubMed

    Ma, Yihe; Bayguinov, Peter O; Jackson, Meyer B

    2017-01-01

    The complex and malleable conduction properties of axons determine how action potentials propagate through extensive axonal arbors to reach synaptic terminals. The excitability of axonal membranes plays a major role in neural circuit function, but because most axons are too thin for conventional electrical recording, their properties remain largely unexplored. To overcome this obstacle, we used a genetically encoded hybrid voltage sensor (hVOS) harboring an axonal targeting motif. Expressing this probe in transgenic mice enabled us to monitor voltage changes optically in two populations of axons in hippocampal slices, the large axons of dentate granule cells (mossy fibers) in the stratum lucidum of the CA3 region and the much finer axons of hilar mossy cells in the inner molecular layer of the dentate gyrus. Action potentials propagated with distinct velocities in each type of axon. Repetitive firing broadened action potentials in both populations, but at an intermediate frequency the degree of broadening differed. Repetitive firing also attenuated action potential amplitudes in both mossy cell and granule cell axons. These results indicate that the features of use-dependent action potential broadening, and possible failure, observed previously in large nerve terminals also appear in much finer unmyelinated axons. Subtle differences in the frequency dependences could influence the propagation of activity through different pathways to excite different populations of neurons. The axonally targeted hVOS probe used here opens up the diverse repertoire of neuronal processes to detailed biophysical study.

  8. Determining potential 30/20 GHZ domestic satellite system concepts and establishment of a suitable experimental configuration

    NASA Technical Reports Server (NTRS)

    Stevens, G. H.; Anzic, G.

    1979-01-01

    NASA is conducting a series of millimeter wave satellite communication systems and market studies to: (1) determine potential domestic 30/20 GHz satellite concepts and market potential, and (2) establish the requirements for a suitable technology verification payload which, although intended to be modest in capacity, would sufficiently demonstrate key technologies and experimentally address key operational issues. Preliminary results and critical issues of the current contracted effort are described. Also included is a description of a NASA-developed multibeam satellite payload configuration which may be representative of concepts utilized in a technology flight verification program.

  9. Simulations of the cardiac action potential based on the Hodgkin-Huxley kinetics with the use of Microsoft Excel spreadsheets.

    PubMed

    Wu, Sheng-Nan

    2004-03-31

    The purpose of this study was to develop a method to simulate the cardiac action potential using a Microsoft Excel spreadsheet. The mathematical model contained voltage-gated ionic currents that were modeled using either Beeler-Reuter (B-R) or Luo-Rudy (L-R) phase 1 kinetics. The simulation protocol involves the use of in-cell formulas directly typed into a spreadsheet. The capability of spreadsheet iteration was used in these simulations. It does not require any prior knowledge of computer programming, although the use of the macro language can speed up the calculation. The normal configuration of the cardiac ventricular action potential can be well simulated in the B-R model that is defined by four individual ionic currents, each representing the diffusion of ions through channels in the membrane. The contribution of Na+ inward current to the rate of depolarization is reproduced in this model. After removal of Na+ current from the model, a constant current stimulus elicits an oscillatory change in membrane potential. In the L-R phase 1 model where six types of ionic currents were defined, the effect of extracellular K+ concentration on changes both in the time course of repolarization and in the time-independent K+ current can be demonstrated, when the solutions are implemented in Excel. Using the simulation protocols described here, the users can readily study and graphically display the underlying properties of ionic currents to see how changes in these properties determine the behavior of the heart cell. The method employed in these simulation protocols may also be extended or modified to other biological simulation programs.

  10. Operational Dynamic Configuration Analysis

    NASA Technical Reports Server (NTRS)

    Lai, Chok Fung; Zelinski, Shannon

    2010-01-01

    Sectors may combine or split within areas of specialization in response to changing traffic patterns. This method of managing capacity and controller workload could be made more flexible by dynamically modifying sector boundaries. Much work has been done on methods for dynamically creating new sector boundaries [1-5]. Many assessments of dynamic configuration methods assume the current day baseline configuration remains fixed [6-7]. A challenging question is how to select a dynamic configuration baseline to assess potential benefits of proposed dynamic configuration concepts. Bloem used operational sector reconfigurations as a baseline [8]. The main difficulty is that operational reconfiguration data is noisy. Reconfigurations often occur frequently to accommodate staff training or breaks, or to complete a more complicated reconfiguration through a rapid sequence of simpler reconfigurations. Gupta quantified a few aspects of airspace boundary changes from this data [9]. Most of these metrics are unique to sector combining operations and not applicable to more flexible dynamic configuration concepts. To better understand what sort of reconfigurations are acceptable or beneficial, more configuration change metrics should be developed and their distribution in current practice should be computed. This paper proposes a method to select a simple sequence of configurations among operational configurations to serve as a dynamic configuration baseline for future dynamic configuration concept assessments. New configuration change metrics are applied to the operational data to establish current day thresholds for these metrics. These thresholds are then corroborated, refined, or dismissed based on airspace practitioner feedback. The dynamic configuration baseline selection method uses a k-means clustering algorithm to select the sequence of configurations and trigger times from a given day of operational sector combination data. The clustering algorithm selects a simplified

  11. Action potentials and ion conductances in wild-type and CALHM1-knockout type II taste cells

    PubMed Central

    Saung, Wint Thu; Foskett, J. Kevin

    2017-01-01

    Taste bud type II cells fire action potentials in response to tastants, triggering nonvesicular ATP release to gustatory neurons via voltage-gated CALHM1-associated ion channels. Whereas CALHM1 regulates mouse cortical neuron excitability, its roles in regulating type II cell excitability are unknown. In this study, we compared membrane conductances and action potentials in single identified TRPM5-GFP-expressing circumvallate papillae type II cells acutely isolated from wild-type (WT) and Calhm1 knockout (KO) mice. The activation kinetics of large voltage-gated outward currents were accelerated in cells from Calhm1 KO mice, and their associated nonselective tail currents, previously shown to be highly correlated with ATP release, were completely absent in Calhm1 KO cells, suggesting that CALHM1 contributes to all of these currents. Calhm1 deletion did not significantly alter resting membrane potential or input resistance, the amplitudes and kinetics of Na+ currents either estimated from action potentials or recorded from steady-state voltage pulses, or action potential threshold, overshoot peak, afterhyperpolarization, and firing frequency. However, Calhm1 deletion reduced the half-widths of action potentials and accelerated the deactivation kinetics of transient outward currents, suggesting that the CALHM1-associated conductance becomes activated during the repolarization phase of action potentials. NEW & NOTEWORTHY CALHM1 is an essential ion channel component of the ATP neurotransmitter release mechanism in type II taste bud cells. Its contribution to type II cell resting membrane properties and excitability is unknown. Nonselective voltage-gated currents, previously associated with ATP release, were absent in cells lacking CALHM1. Calhm1 deletion was without effects on resting membrane properties or voltage-gated Na+ and K+ channels but contributed modestly to the kinetics of action potentials. PMID:28202574

  12. Action potentials and ion conductances in wild-type and CALHM1-knockout type II taste cells.

    PubMed

    Ma, Zhongming; Saung, Wint Thu; Foskett, J Kevin

    2017-05-01

    Taste bud type II cells fire action potentials in response to tastants, triggering nonvesicular ATP release to gustatory neurons via voltage-gated CALHM1-associated ion channels. Whereas CALHM1 regulates mouse cortical neuron excitability, its roles in regulating type II cell excitability are unknown. In this study, we compared membrane conductances and action potentials in single identified TRPM5-GFP-expressing circumvallate papillae type II cells acutely isolated from wild-type (WT) and Calhm1 knockout (KO) mice. The activation kinetics of large voltage-gated outward currents were accelerated in cells from Calhm1 KO mice, and their associated nonselective tail currents, previously shown to be highly correlated with ATP release, were completely absent in Calhm1 KO cells, suggesting that CALHM1 contributes to all of these currents. Calhm1 deletion did not significantly alter resting membrane potential or input resistance, the amplitudes and kinetics of Na + currents either estimated from action potentials or recorded from steady-state voltage pulses, or action potential threshold, overshoot peak, afterhyperpolarization, and firing frequency. However, Calhm1 deletion reduced the half-widths of action potentials and accelerated the deactivation kinetics of transient outward currents, suggesting that the CALHM1-associated conductance becomes activated during the repolarization phase of action potentials. NEW & NOTEWORTHY CALHM1 is an essential ion channel component of the ATP neurotransmitter release mechanism in type II taste bud cells. Its contribution to type II cell resting membrane properties and excitability is unknown. Nonselective voltage-gated currents, previously associated with ATP release, were absent in cells lacking CALHM1. Calhm1 deletion was without effects on resting membrane properties or voltage-gated Na + and K + channels but contributed modestly to the kinetics of action potentials. Copyright © 2017 the American Physiological Society.

  13. Population of computational rabbit-specific ventricular action potential models for investigating sources of variability in cellular repolarisation.

    PubMed

    Gemmell, Philip; Burrage, Kevin; Rodriguez, Blanca; Quinn, T Alexander

    2014-01-01

    Variability is observed at all levels of cardiac electrophysiology. Yet, the underlying causes and importance of this variability are generally unknown, and difficult to investigate with current experimental techniques. The aim of the present study was to generate populations of computational ventricular action potential models that reproduce experimentally observed intercellular variability of repolarisation (represented by action potential duration) and to identify its potential causes. A systematic exploration of the effects of simultaneously varying the magnitude of six transmembrane current conductances (transient outward, rapid and slow delayed rectifier K(+), inward rectifying K(+), L-type Ca(2+), and Na(+)/K(+) pump currents) in two rabbit-specific ventricular action potential models (Shannon et al. and Mahajan et al.) at multiple cycle lengths (400, 600, 1,000 ms) was performed. This was accomplished with distributed computing software specialised for multi-dimensional parameter sweeps and grid execution. An initial population of 15,625 parameter sets was generated for both models at each cycle length. Action potential durations of these populations were compared to experimentally derived ranges for rabbit ventricular myocytes. 1,352 parameter sets for the Shannon model and 779 parameter sets for the Mahajan model yielded action potential duration within the experimental range, demonstrating that a wide array of ionic conductance values can be used to simulate a physiological rabbit ventricular action potential. Furthermore, by using clutter-based dimension reordering, a technique that allows visualisation of multi-dimensional spaces in two dimensions, the interaction of current conductances and their relative importance to the ventricular action potential at different cycle lengths were revealed. Overall, this work represents an important step towards a better understanding of the role that variability in current conductances may play in experimentally

  14. Population of Computational Rabbit-Specific Ventricular Action Potential Models for Investigating Sources of Variability in Cellular Repolarisation

    PubMed Central

    Gemmell, Philip; Burrage, Kevin; Rodriguez, Blanca; Quinn, T. Alexander

    2014-01-01

    Variability is observed at all levels of cardiac electrophysiology. Yet, the underlying causes and importance of this variability are generally unknown, and difficult to investigate with current experimental techniques. The aim of the present study was to generate populations of computational ventricular action potential models that reproduce experimentally observed intercellular variability of repolarisation (represented by action potential duration) and to identify its potential causes. A systematic exploration of the effects of simultaneously varying the magnitude of six transmembrane current conductances (transient outward, rapid and slow delayed rectifier K+, inward rectifying K+, L-type Ca2+, and Na+/K+ pump currents) in two rabbit-specific ventricular action potential models (Shannon et al. and Mahajan et al.) at multiple cycle lengths (400, 600, 1,000 ms) was performed. This was accomplished with distributed computing software specialised for multi-dimensional parameter sweeps and grid execution. An initial population of 15,625 parameter sets was generated for both models at each cycle length. Action potential durations of these populations were compared to experimentally derived ranges for rabbit ventricular myocytes. 1,352 parameter sets for the Shannon model and 779 parameter sets for the Mahajan model yielded action potential duration within the experimental range, demonstrating that a wide array of ionic conductance values can be used to simulate a physiological rabbit ventricular action potential. Furthermore, by using clutter-based dimension reordering, a technique that allows visualisation of multi-dimensional spaces in two dimensions, the interaction of current conductances and their relative importance to the ventricular action potential at different cycle lengths were revealed. Overall, this work represents an important step towards a better understanding of the role that variability in current conductances may play in experimentally observed

  15. Conduction velocity of action potentials measured from unidimensional latency-topography in human and frog skeletal muscle fibers.

    PubMed

    Homma, S; Nakajima, Y; Hayashi, K; Toma, S

    1986-01-01

    Conduction of an action potential along skeletal muscle fibers was graphically displayed by unidimensional latency-topography, UDLT. Since the slopes of the equipotential line were linear and the width of the line was constant, it was possible to calculate conduction velocity from the slope. To determine conduction direction of the muscle action potential elicited by electric stimulation applied directly to the muscle, surface recording electrodes were placed on a two-dimensional plane over a human muscle. Thus a bi-dimensional topography was obtained. Then, twelve or sixteen surface electrodes were placed linearly along the longitudinal direction of the action potential conduction which was disclosed by the bi-dimensional topography. Thus conduction velocity of muscle action potential in man, calculated from the slope, was for m. brachioradialis, 3.9 +/- 0.4 m/s; for m. biceps brachii, 3.6 +/- 0.2 m/s; for m. sternocleidomastoideus, 3.6 +/- 0.4 m/s. By using a tungsten microelectrode to stimulate the motor axons, a convex-like equipotential line of an action potential in UDLT was obtained from human muscle fibers. Since a similar pattern of UDLT was obtained from experiments on isolated frog muscles, in which the muscle action potential was elicited by stimulating the motor axon, it was assumed that the maximum of the curve corresponds to the end-plate region, and that the slopes on both sides indicate bi-directional conduction of the action potential.

  16. Activation of cannabinoid CB1 receptors modulates evoked action potentials in rat retinal ganglion cells.

    PubMed

    Jiang, Shu-Xia; Li, Qian; Wang, Xiao-Han; Li, Fang; Wang, Zhong-Feng

    2013-08-25

    Activation of cannabinoid CB1 receptors (CB1Rs) regulates a variety of physiological functions in the vertebrate retina through modulating various types of ion channels. The aim of the present study was to investigate the effects of this receptor on cell excitability of rat retinal ganglion cells (RGCs) in retinal slices using whole-cell patch-clamp techniques. The results showed that under current-clamped condition perfusing WIN55212-2 (WIN, 5 μmol/L), a CB1R agonist, did not significantly change the spontaneous firing frequency and resting membrane potential of RGCs. In the presence of cocktail synaptic blockers, including excitatory postsynaptic receptor blockers CNQX and D-APV, and inhibitory receptor blockers bicuculline and strychnine, perfusion of WIN (5 μmol/L) hardly changed the frequencies of evoked action potentials by a series of positive current injection (from +10 to +100 pA). Phase-plane plot analysis showed that both average threshold voltage for triggering action potential and delay time to reach threshold voltage were not affected by WIN. However, WIN significantly decreased +dV/dtmax and -dV/dtmax of action potentials, suggestive of reduced rising and descending velocities of action potentials. The effects of WIN were reversed by co-application of SR141716, a CB1R selective antagonist. Moreover, WIN did not influence resting membrane potential of RGCs with synaptic inputs being blocked. These results suggest that activation of CB1Rs may regulate intrinsic excitability of rat RGCs through modulating evoked action potentials.

  17. An indirect component in the evoked compound action potential of the vagal nerve.

    PubMed

    Ordelman, Simone C M A; Kornet, Lilian; Cornelussen, Richard; Buschman, Hendrik P J; Veltink, Peter H

    2010-12-01

    The vagal nerve plays a vital role in the regulation of the cardiovascular system. It not only regulates the heart but also sends sensory information from the heart back to the brain. We hypothesize that the evoked vagal nerve compound action potential contains components that are indirect via the brain stem or coming via the neural network on the heart. In an experimental study of 15 pigs, we identified four components in the evoked compound action potentials. The fourth component was found to be an indirect component, which came from the periphery. The latency of the indirect component increased when heart rate and contractility were decreased by burst stimulation (P = 0.01; n = 7). When heart rate and contractility were increased by dobutamine administration, the latency of the indirect component decreased (P = 0.01; n = 9). This showed that the latency of the indirect component of the evoked compound action potentials may relate to the state of the cardiovascular system.

  18. The Direct Detection of a Single Evoked Action Potential with Magnetic Resonance Spectroscopy in Lumbricus Terrestris

    PubMed Central

    Poplawsky, Alexander J.; Dingledine, Raymond

    2011-01-01

    Functional MRI (fMRI) indirectly measures neural activity by detecting the signal change associated with the hemodynamic response following brain activation. In order to alleviate the temporal and spatial specificity problems associated with fMRI, a number of attempts have been made to detect neural magnetic fields (NMFs) with MRI directly, but have thus far provided conflicting results. In the present study, we used magnetic resonance to detect axonal NMFs in the median giant fiber of the earthworm, Lumbricus terrestris, by examining the free-induction decay (FID) with a sampling interval of 0.32 ms. The earthworm nerve cords were isolated from the vasculature and stimulated at the threshold of action potential generation. FIDs were acquired shortly after the stimulation and simultaneous field potential recordings identified the presence or absence of single evoked action potentials. FIDs acquired when the stimulus did not evoke an action potential were summed as background. The phase of the background-subtracted FID exhibited a systematic change, with a peak phase difference of [-1.2 ± 0.3] ×10-5 radians occurring at a time corresponding to the timing of the action potential. In addition, we calculated the possible changes in the FID magnitude and phase due to a simulated action potential using a volume conductor model. The measured phase difference matched the theoretical prediction well in both amplitude and temporal characteristics. This study provides the first evidence for the direct detection of a magnetic field from an evoked action potential using magnetic resonance. PMID:21728204

  19. Simulation of action potentials from metabolically impaired cardiac myocytes. Role of ATP-sensitive K+ current.

    PubMed

    Ferrero, J M; Sáiz, J; Ferrero, J M; Thakor, N V

    1996-08-01

    The role of the ATP-sensitive K+ current (IK-ATP) and its contribution to electrophysiological changes that occur during metabolic impairment in cardiac ventricular myocytes is still being discussed. The aim of this work was to quantitatively study this issue by using computer modeling. A model of IK-ATP is formulated and incorporated into the Luo-Rudy ionic model of the ventricular action potential. Action potentials under different degrees of activation of IK-ATP are simulated. Our results show that in normal ionic concentrations, only approximately 0.6% of the KATP channels, when open, should account for a 50% reduction in action potential duration. However, increased levels of intracellular Mg2+ counteract this shortening. Under conditions of high [K+]0, such as those found in early ischemia, the activation of only approximately 0.4% of the KATP channels could account for a 50% reduction in action potential duration. Thus, our results suggest that opening of IK-ATP channels should play a significant role in action potential shortening during hypoxic/ischemic episodes, with the fraction of open channels involved being very low ( < 1%). However, the results of the model suggest that activation of IK-ATP alone does not quantitatively account for the observed K+ efflux in metabolically impaired cardiac myocytes. Mechanisms other than KATP channel activation should be responsible for a significant part of the K+ efflux measured in hypoxic/ischemic situations.

  20. Cardiac action potential repolarization revisited: early repolarization shows all-or-none behaviour.

    PubMed

    Trenor, Beatriz; Cardona, Karen; Saiz, Javier; Noble, Denis; Giles, Wayne

    2017-11-01

    In healthy mammalian hearts the action potential (AP) waveform initiates and modulates each contraction, or heartbeat. As a result, AP height and duration are key physiological variables. In addition, rate-dependent changes in ventricular AP duration (APD), and variations in APD at a fixed heart rate are both reliable biomarkers of electrophysiological stability. Present guidelines for the likelihood that candidate drugs will increase arrhythmias rely on small changes in APD and Q-T intervals as criteria for safety pharmacology decisions. However, both of these measurements correspond to the final repolarization of the AP. Emerging clinical evidence draws attention to the early repolarization phase of the action potential (and the J-wave of the ECG) as an additional important biomarker for arrhythmogenesis. Here we provide a mechanistic background to this early repolarization syndrome by summarizing the evidence that both the initial depolarization and repolarization phases of the cardiac action potential can exhibit distinct time- and voltage-dependent thresholds, and also demonstrating that both can show regenerative all-or-none behaviour. An important consequence of this is that not all of the dynamics of action potential repolarization in human ventricle can be captured by data from single myocytes when these results are expressed as 'repolarization reserve'. For example, the complex pattern of cell-to-cell current flow that is responsible for AP conduction (propagation) within the mammalian myocardium can change APD and the Q-T interval of the electrocardiogram alter APD stability, and modulate responsiveness to pharmacological agents (such as Class III anti-arrhythmic drugs). © 2017 The Authors. The Journal of Physiology © 2017 The Physiological Society.

  1. [Effects of dauricine on action potentials and slow inward currents of guinea pig ventricular papillary muscles].

    PubMed

    Li, S N; Zhang, K Y

    1992-11-01

    Effects of dauricine (Dau) on the action potentials (AP), the slow action potentials (SAP), and the slow inward currents (Isi) of guinea pig ventricular papillary muscles were observed by means of intracellular microelectrode and single sucrose gap voltage clamp technique. In the early stage, Dau shortened action potential duration 100 (APD100) and effective refractory period (ERP) (ERP/APD < 1; P < 0.01), but did not affect APD20 and other parameters. In the late stage, Dau prolonged APD100, ERP, and APD20, significantly decreased action potential amplitude (APA), maximum velocity (Vmax), and overshot (OS) (ERP/APD > 1; P < 0.01), greatly diminished APA and OS of SAP induced by isoprenaline (P < 0.01), and remarkably inhibited Isi (P < 0.01). The results suggested that Dau exerted an inhibitory effect on Na+, Ca2+, and K+ channels.

  2. Accession-dependent action potentials in Arabidopsis.

    PubMed

    Favre, Patrick; Greppin, Hubert; Degli Agosti, Robert

    2011-05-01

    Plant excitability, as measured by the appearance and circulation of action potentials (APs) after biotic and abiotic stress treatments, is a far lesser and more versatile phenomenon than in animals. To examine the genetic basis of plant excitability we used different Arabidopsis thaliana accessions. APs were induced by wounding (W) with a subsequent deposition (D) of 5μL of 1M KCl onto adult leaves. This treatment elicited transient voltage responses (APs) that were detected by 2 extracellular electrodes placed at a distance from the wounding location over an experimental time of 150min. The first electrode (e1) was placed at the end of the petiole and the beginning of the leaf, and the second (e2) electrode was placed on the petiole near the center of the rosette. All accessions (Columbia (Col), Wassilewskija (Ws) and Landsberg erecta (Ler)) responded to the W & D treatment. After W & D treatment was performed on 100 plants for each accession, the number of APs ranged from 0 to 37 (median 8, total 940), 0 to 16 (median 5, total 528) and 0 to 18 (median 2, total 296) in Col, Ws and Ler, respectively. Responding plants (>0 APs) showed significantly different behaviors depending on their accessions of origin (i.e., Col 91, Ws 83 and Ler 76%). Some AP characteristics, such as amplitude and speed of propagation from e1 to e2 (1.28mms(-1)), were the same for all accessions, whereas the average duration of APs was similar in Col and Ws, but different in Ler. Self-sustained oscillations were observed more frequently in Col than Ws and least often in Ler, and the mean oscillation frequency was more rapid in Col, followed by Ws, and was slowest in Ler. In general, Col was the most excitable accession, followed by Ws, and Ler was the least excitable; this corresponded well with voltage elicited action potentials. In conclusion, part of Arabidopsis excitability in AP responses is genetically pre-determined. Copyright © 2010 Elsevier GmbH. All rights reserved.

  3. Prehension synergies and control with referent hand configurations.

    PubMed

    Latash, Mark L; Friedman, Jason; Kim, Sun Wook; Feldman, Anatol G; Zatsiorsky, Vladimir M

    2010-04-01

    We used the framework of the equilibrium-point hypothesis (in its updated form based on the notion of referent configuration) to investigate the multi-digit synergies at two levels of a hypothetical hierarchy involved in prehensile actions. Synergies were analyzed at the thumb-virtual finger (VF) level (VF is an imaginary digit with the mechanical action equivalent to that of the four actual fingers) and at the individual finger level. The subjects performed very quick vertical movements of a handle into a target. A load could be attached off-center to provide a pronation or supination torque. In a few trials, the handle was unexpectedly fixed to the table and the digits slipped off the sensors. In such trials, the hand stopped at a higher vertical position and rotated into pronation or supination depending on the expected torque. The aperture showed non-monotonic changes with a large, fast decrease and further increase, ending up with a smaller distance between the thumb and the fingers as compared to unperturbed trials. Multi-digit synergies were quantified using indices of co-variation between digit forces and moments of force across unperturbed trials. Prior to the lifting action, high synergy indices were observed at the individual finger level while modest indices were observed at the thumb-VF level. During the lifting action, the synergies at the individual finger level disappeared while the synergy indices became higher at the thumb-VF level. The results support the basic premise that, within a given task, setting a referent configuration may be described with a few referent values of variables that influence the equilibrium state, to which the system is attracted. Moreover, the referent configuration hypothesis can help interpret the data related to the trade-off between synergies at different hierarchical levels.

  4. Surface deformation during an action potential in pearled cells

    NASA Astrophysics Data System (ADS)

    Mussel, Matan; Fillafer, Christian; Ben-Porath, Gal; Schneider, Matthias F.

    2017-11-01

    Electric pulses in biological cells (action potentials) have been reported to be accompanied by a propagating cell-surface deformation with a nanoscale amplitude. Typically, this cell surface is covered by external layers of polymer material (extracellular matrix, cell wall material, etc.). It was recently demonstrated in excitable plant cells (Chara braunii) that the rigid external layer (cell wall) hinders the underlying deformation. When the cell membrane was separated from the cell wall by osmosis, a mechanical deformation, in the micrometer range, was observed upon excitation of the cell. The underlying mechanism of this mechanical pulse has, to date, remained elusive. Herein we report that Chara cells can undergo a pearling instability, and when the pearled fragments were excited even larger and more regular cell shape changes were observed (˜10 -100 μ m in amplitude). These transient cellular deformations were captured by a curvature model that is based on three parameters: surface tension, bending rigidity, and pressure difference across the surface. In this paper these parameters are extracted by curve-fitting to the experimental cellular shapes at rest and during excitation. This is a necessary step to identify the mechanical parameters that change during an action potential.

  5. Electrotonic and action potentials in the Venus flytrap.

    PubMed

    Volkov, Alexander G; Vilfranc, Chrystelle L; Murphy, Veronica A; Mitchell, Colee M; Volkova, Maia I; O'Neal, Lawrence; Markin, Vladislav S

    2013-06-15

    The electrical phenomena and morphing structures in the Venus flytrap have attracted researchers since the nineteenth century. We have observed that mechanical stimulation of trigger hairs on the lobes of the Venus flytrap induces electrotonic potentials in the lower leaf. Electrostimulation of electrical circuits in the Venus flytrap can induce electrotonic potentials propagating along the upper and lower leaves. The instantaneous increase or decrease in voltage of stimulating potential generates a nonlinear electrical response in plant tissues. Any electrostimulation that is not instantaneous, such as sinusoidal or triangular functions, results in linear responses in the form of small electrotonic potentials. The amplitude and sign of electrotonic potentials depend on the polarity and the amplitude of the applied voltage. Electrical stimulation of the lower leaf induces electrical signals, which resemble action potentials, in the trap between the lobes and the midrib. The trap closes if the stimulating voltage is above the threshold level of 4.4V. Electrical responses in the Venus flytrap were analyzed and reproduced in the discrete electrical circuit. The information gained from this study can be used to elucidate the coupling of intracellular and intercellular communications in the form of electrical signals within plants. Copyright © 2013 Elsevier GmbH. All rights reserved.

  6. Pulsed magnetic stimulation modifies amplitude of action potentials in vitro via ionic channels-dependent mechanism.

    PubMed

    Ahmed, Zaghloul; Wieraszko, Andrzej

    2015-07-01

    This paper investigates the influence of pulsed magnetic fields (PMFs) on amplitude of evoked, compound action potential (CAP) recorded from the segments of sciatic nerve in vitro. PMFs were applied for 30 min at frequency of 0.16 Hz and intensity of 15 mT. In confirmation of our previous reports, PMF exposure enhanced amplitude of CAPs. The effect persisted beyond PMF activation period. As expected, CAP amplitude was attenuated by antagonists of sodium channel, lidocaine, and tetrodotoxin. Depression of the potential by sodium channels antagonists was reversed by subsequent exposure to PMFs. The effect of elevated potassium concentration and veratridine on the action potential was modified by exposure to PMFs as well. Neither inhibitors of protein kinase C and protein kinase A, nor known free radicals scavengers had any effects on PMF action. Possible mechanisms of PMF action are discussed. © 2015 Wiley Periodicals, Inc.

  7. Millisecond infrared laser pulses depolarize and elicit action potentials on in-vitro dorsal root ganglion neurons

    PubMed Central

    Paris, Lambert; Marc, Isabelle; Charlot, Benoit; Dumas, Michel; Valmier, Jean; Bardin, Fabrice

    2017-01-01

    This work focuses on the optical stimulation of dorsal root ganglion (DRG) neurons through infrared laser light stimulation. We show that a few millisecond laser pulse at 1875 nm induces a membrane depolarization, which was observed by the patch-clamp technique. This stimulation led to action potentials firing on a minority of neurons beyond an energy threshold. A depolarization without action potential was observed for the majority of DRG neurons, even beyond the action potential energy threshold. The use of ruthenium red, a thermal channel blocker, stops the action potential generation, but has no effects on membrane depolarization. Local temperature measurements reveal that the depolarization amplitude is sensitive to the amplitude of the temperature rise as well as to the time rate of change of temperature, but in a way which may not fully follow a photothermal capacitive mechanism, suggesting that more complex mechanisms are involved. PMID:29082085

  8. Rapid time course of action potentials in spines and remote dendrites of mouse visual cortex neurons.

    PubMed

    Holthoff, Knut; Zecevic, Dejan; Konnerth, Arthur

    2010-04-01

    Axonally initiated action potentials back-propagate into spiny dendrites of central mammalian neurons and thereby regulate plasticity at excitatory synapses on individual spines as well as linear and supralinear integration of synaptic inputs along dendritic branches. Thus, the electrical behaviour of individual dendritic spines and terminal dendritic branches is critical for the integrative function of nerve cells. The actual dynamics of action potentials in spines and terminal branches, however, are not entirely clear, mostly because electrode recording from such small structures is not feasible. Additionally, the available membrane potential imaging techniques are limited in their sensitivity and require substantial signal averaging for the detection of electrical events at the spatial scale of individual spines. We made a critical improvement in the voltage-sensitive dye imaging technique to achieve multisite recordings of backpropagating action potentials from individual dendritic spines at a high frame rate. With this approach, we obtained direct evidence that in layer 5 pyramidal neurons from the visual cortex of juvenile mice, the rapid time course of somatic action potentials is preserved throughout all cellular compartments, including dendritic spines and terminal branches of basal and apical dendrites. The rapid time course of the action potential in spines may be a critical determinant for the precise regulation of spike timing-dependent synaptic plasticity within a narrow time window.

  9. Label-free optical detection of action potential in mammalian neurons (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Batabyal, Subrata; Satpathy, Sarmishtha; Bui, Loan; Kim, Young-Tae; Mohanty, Samarendra K.; Davé, Digant P.

    2017-02-01

    Electrophysiology techniques are the gold standard in neuroscience for studying functionality of a single neuron to a complex neuronal network. However, electrophysiology techniques are not flawless, they are invasive nature, procedures are cumbersome to implement with limited capability of being used as a high-throughput recording system. Also, long term studies of neuronal functionality with aid of electrophysiology is not feasible. Non-invasive stimulation and detection of neuronal electrical activity has been a long standing goal in neuroscience. Introduction of optogenetics has ushered in the era of non-invasive optical stimulation of neurons, which is revolutionizing neuroscience research. Optical detection of neuronal activity that is comparable to electro-physiology is still elusive. A number of optical techniques have been reported recording of neuronal electrical activity but none is capable of reliably measuring action potential spikes that is comparable to electro-physiology. Optical detection of action potential with voltage sensitive fluorescent reporters are potential alternatives to electrophysiology techniques. The heavily rely on secondary reporters, which are often toxic in nature with background fluorescence, with slow response and low SNR making them far from ideal. The detection of one shot (without averaging)-single action potential in a true label-free way has been elusive so far. In this report, we demonstrate the optical detection of single neuronal spike in a cultured mammalian neuronal network without using any exogenous labels. To the best of our knowledge, this is the first demonstration of label free optical detection of single action potentials in a mammalian neuronal network, which was achieved using a high-speed phase sensitive interferometer. We have carried out stimulation and inhibition of neuronal firing using Glutamate and Tetrodotoxin respectively to demonstrate the different outcome (stimulation and inhibition) revealed in

  10. Urocortin2 prolongs action potential duration and modulates potassium currents in guinea pig myocytes and HEK293 cells.

    PubMed

    Yang, Li-Zhen; Zhu, Yi-Chun

    2015-07-05

    We previously reported that activation of corticotropin releasing factor receptor type 2 by urocortin2 up-regulates both L-type Ca(2+) channels and intracellular Ca(2+) concentration in ventricular myocytes and plays an important role in cardiac contractility and arrhythmogenesis. This study goal was to further test the hypothesis that urocortin2 may modulate action potentials as well as rapidly and slowly activating delayed rectifier potassium currents. With whole cell patch-clamp techniques, action potentials and slowly activating delayed rectifier potassium currents were recorded in isolated guinea pig ventricular myocytes, respectively. And rapidly activating delayed rectifier potassium currents were tested in hERG-HEK293 cells. Urocortin2 produced a time- and concentration-dependent prolongation of action potential duration. The EC50 values of action potential duration and action potential duration at 90% of repolarization were 14.73 and 24.3nM respectively. The prolongation of action potential duration of urocortin2 was almost completely or partly abolished by H-89 (protein kinase A inhibitor) or KB-R7943 (Na(+)/Ca(2+) exchange inhibitor) pretreatment respectively. And urocortin2 caused reduction of rapidly activating delayed rectifier potassium currents in hERG-HEK293 cells. In addition, urocortin2 slowed the rate of slowly activating delayed rectifier potassium channel activation, and rightward shifted the threshold of slowly activating delayed rectifier potassium currents to more positive potentials. Urocortin2 prolonged action potential duration via activation of protein kinase A and Na(+)/ Ca(2+) exchange in isolated guinea pig ventricular myocytes in a time- and concentration- dependent manner. In hERG-HEK293 cells, urocortin2 reduced rapidly activating delayed rectifier potassium current density which may contribute to action potential duration prolongation. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. Automated grouping of action potentials of human embryonic stem cell-derived cardiomyocytes.

    PubMed

    Gorospe, Giann; Zhu, Renjun; Millrod, Michal A; Zambidis, Elias T; Tung, Leslie; Vidal, Rene

    2014-09-01

    Methods for obtaining cardiomyocytes from human embryonic stem cells (hESCs) are improving at a significant rate. However, the characterization of these cardiomyocytes (CMs) is evolving at a relatively slower rate. In particular, there is still uncertainty in classifying the phenotype (ventricular-like, atrial-like, nodal-like, etc.) of an hESC-derived cardiomyocyte (hESC-CM). While previous studies identified the phenotype of a CM based on electrophysiological features of its action potential, the criteria for classification were typically subjective and differed across studies. In this paper, we use techniques from signal processing and machine learning to develop an automated approach to discriminate the electrophysiological differences between hESC-CMs. Specifically, we propose a spectral grouping-based algorithm to separate a population of CMs into distinct groups based on the similarity of their action potential shapes. We applied this method to a dataset of optical maps of cardiac cell clusters dissected from human embryoid bodies. While some of the nine cell clusters in the dataset are presented with just one phenotype, the majority of the cell clusters are presented with multiple phenotypes. The proposed algorithm is generally applicable to other action potential datasets and could prove useful in investigating the purification of specific types of CMs from an electrophysiological perspective.

  12. Automated Grouping of Action Potentials of Human Embryonic Stem Cell-Derived Cardiomyocytes

    PubMed Central

    Gorospe, Giann; Zhu, Renjun; Millrod, Michal A.; Zambidis, Elias T.; Tung, Leslie; Vidal, René

    2015-01-01

    Methods for obtaining cardiomyocytes from human embryonic stem cells (hESCs) are improving at a significant rate. However, the characterization of these cardiomyocytes is evolving at a relatively slower rate. In particular, there is still uncertainty in classifying the phenotype (ventricular-like, atrial-like, nodal-like, etc.) of an hESC-derived cardiomyocyte (hESC-CM). While previous studies identified the phenotype of a cardiomyocyte based on electrophysiological features of its action potential, the criteria for classification were typically subjective and differed across studies. In this paper, we use techniques from signal processing and machine learning to develop an automated approach to discriminate the electrophysiological differences between hESC-CMs. Specifically, we propose a spectral grouping-based algorithm to separate a population of cardiomyocytes into distinct groups based on the similarity of their action potential shapes. We applied this method to a dataset of optical maps of cardiac cell clusters dissected from human embryoid bodies (hEBs). While some of the 9 cell clusters in the dataset presented with just one phenotype, the majority of the cell clusters presented with multiple phenotypes. The proposed algorithm is generally applicable to other action potential datasets and could prove useful in investigating the purification of specific types of cardiomyocytes from an electrophysiological perspective. PMID:25148658

  13. Passive Responses Resembling Action Potentials: A Device for the Classroom

    ERIC Educational Resources Information Center

    Newman, Ian A.; Pickard, Barbara G.

    1975-01-01

    Describes the construction and operation of a network of entirely passive electrical components that gives a response to an electrical shock similar to an action potential. The network of resistors, capacitors, and diodes was developed to produce responses that would mimic those observed, for example, when a dark-grown pea epicotyl is shocked…

  14. Minima de L'intégrale D'action du Problème Newtoniende 4 Corps de Masses Égales Dans R3: Orbites `Hip-Hop'

    NASA Astrophysics Data System (ADS)

    Chenciner, Alain; Venturelli, Andrea

    2000-09-01

    We consider the problem of 4 bodies of equal masses in R 3 for the Newtonian r-1 potential. We address the question of the absolute minima of the action integral among (anti)symmetric loops of class H 1 whose period is fixed. It is the simplest case for which the results of [4] (corrected in [5]) do not apply: the minima cannot be the relative equilibria whose configuration is an absolute minimum of the potential among the configurations having a given moment of inertia with respect to their center of mass. This is because the regular tetrahedron cannot have a relative equilibrium motion in R 3 (see [2]). We show that the absolute minima of the action are not homographic motions. We also show that if we force the configuration to admit a certain type of symmetry of order 4, the absolute minimum is a collisionless orbit whose configuration ‘hesitates’ between the central configuration of the square and the one of the tetrahedron. We call these orbits ‘hip-hop’. A similar result holds in case of a symmetry of order 3 where the central configuration of the equilateral triangle with a body at the center of mass replaces the square.

  15. Note on tachyon actions in string theory

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Headrick, Matthew

    2009-02-15

    A number of spacetime fields in string theory (notably the metric, dilaton, bosonic and type 0 bulk closed-string tachyon, and bosonic open-string tachyon) have the following property: whenever the spacetime field configuration factorizes in an appropriate sense, the matter sector of the world-sheet theory factorizes into a tensor product of two decoupled theories. Since the beta functions for such a product theory necessarily also factorize, this property strongly constrains the form of the spacetime action encoding those beta functions. We show that this constraint alone--without needing actually to compute any of the beta functions--is sufficient to fix the form ofmore » the two-derivative action for the metric-dilaton system, as well as the potential for the bosonic open-string tachyon. We also show that no action consistent with this constraint exists for the closed-string tachyon coupled to the metric and dilaton.« less

  16. Estimating the duration of intracellular action potentials in muscle fibres from single-fibre extracellular potentials.

    PubMed

    Rodríguez, Javier; Navallas, Javier; Gila, Luis; Dimitrova, Nonna Alexandrovna; Malanda, Armando

    2011-04-30

    In situ recording of the intracellular action potential (IAP) of human muscle fibres is not yet possible, and consequently, knowledge concerning certain IAP characteristics is still limited. According to the core-conductor theory, close to a fibre, a single fibre action potential (SFAP) can be assumed to be proportional to the IAP second derivative. Thus, we might expect to be able to derive some characteristics of the IAP, such as the duration of its spike, from the SFAP waveform. However, SFAP properties not only depend on the IAP shape but also on the fibre-to-electrode (radial) distance and other physiological properties of the fibre. In this paper we, first, propose an SFAP parameter (the negative phase duration, NPD) appropriate for estimating the IAP spike duration and, second, show that this parameter is largely independent of changes in radial distance and muscle fibre propagation velocity. Estimation of the IAP spike duration from a direct measurement taken from the SFAP waveform provides a possible way to enhance the accuracy of SFAP models. Because IAP spike duration is known to be sensitive to the effects of fatigue and calcium accumulation, the proposed SFAP parameter, the NPD, has potential value in electrodiagnosis and as an indicator of IAP profile changes due to peripheral fatigue. Copyright © 2011 Elsevier B.V. All rights reserved.

  17. The Potential of Deweyan-Inspired Action Research

    ERIC Educational Resources Information Center

    Stark, Jody L.

    2014-01-01

    In its broadest sense, pragmatism could be said to be the philosophical orientation of all action research. Action research is characterized by research, action, and participation grounded in democratic principles and guided by the aim of social improvement. Furthermore, action research is an active process of inquiry that does not admit…

  18. Human stem cell-derived cardiomyocytes detect drug-mediated changes in action potentials and ion currents.

    PubMed

    Gibson, John K; Yue, Yimei; Bronson, Jared; Palmer, Cassie; Numann, Randy

    2014-01-01

    It has been proposed that proarrhythmia assessment for safety pharmacology testing includes the use of human pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) to detect drug-induced changes in cardiac electrophysiology. This study measured the actions of diverse agents on action potentials (AP) and ion currents recorded from hiPSC-CM. During AP experiments, the hiPSC-CM were paced at 1Hz during a baseline period, and when increasing concentrations of test compound were administered at 4-minute intervals. AP parameters, including duration (APD60 and APD90), resting membrane potential, rate of rise, and amplitude, were measured throughout the entire experiment. Voltage clamp experiments with E-4031 and nifedipine were similarly conducted. E-4031 produced a dose-dependent prolongation of cardiac action potential and blocked the hERG/IKr current with an IC50 of 17nM. At 3nM, dofetilide significantly increased APD90. Astemizole significantly increased APD60 and APD90 at 30nM. Terfenadine significantly increased APD90 at concentrations greater than 10nM. Fexofenadine, a metabolite of terfenadine, did not produce any electrophysiologic changes in cardiac action potentials. Flecainide produced a dose-dependent prolongation of the cardiac action potential at 1 and 3μM. Acute exposure to nifedipine significantly decreased APD60 and APD90 and produced a dose-dependent block of calcium current with an IC50 of 0.039μM. Verapamil first shortened APD60 and APD90 in a dose-dependent manner, until a compensating increase in APD90, presumably via hERG blockade, was observed at 1 and 3μM. Following a chronic exposure (20-24h) to clinically relevant levels of pentamidine, a significant increase in action potential duration was accompanied by early afterdepolarizations (EADs). These experiments show the ability of AP measured from hiPSC-CM to record the interactions of various ion channels via AP recording and avoid the limitations of using several single ion channel assays in

  19. Effects of K(+) channel openers on spontaneous action potentials in detrusor smooth muscle of the guinea-pig urinary bladder.

    PubMed

    Takagi, Hiroaki; Hashitani, Hikaru

    2016-10-15

    The modulation of spontaneous excitability in detrusor smooth muscle (DSM) upon the pharmacological activation of different populations of K(+) channels was investigated. Effects of distinct K(+) channel openers on spontaneous action potentials in DSM of the guinea-pig bladder were examined using intracellular microelectrode techniques. NS1619 (10μM), a large conductance Ca(2+)-activated K(+) (BK) channel opener, transiently increased action potential frequency and then prevented their generation without hyperpolarizing the membrane in a manner sensitive to iberiotoxin (IbTX, 100nM). A higher concentration of NS1619 (30μM) hyperpolarized the membrane and abolished action potential firing. NS309 (10μM) and SKA31 (100μM), small conductance Ca(2+)-activated K(+) (SK) channel openers, dramatically increased the duration of the after-hyperpolarization and then abolished action potential firing in an apamin (100nM)-sensitive manner. Flupirtine (10μM), a Kv7 channel opener, inhibited action potential firing without hyperpolarizing the membrane in a manner sensitive to XE991 (10μM), a Kv7 channel blocker. BRL37344 (10μM), a β3-adrenceptor agonist, or rolipram (10nM), a phosphodiesterase 4 inhibitor, also inhibited action potential firing. A higher concentration of rolipram (100nM) hyperpolarized the DSM and abolished the action potentials. IbTX (100nM) prevented the rolipram-induced blockade of action potentials but not the hyperpolarization. BK and Kv7 channels appear to predominantly contribute to the stabilization of DSM excitability. Spare SK channels could be pharmacologically activated to suppress DSM excitability. BK channels appear to be involved in the cyclic AMP-induced inhibition of action potentials but not the membrane hyperpolarization. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Inhibition by TRPA1 agonists of compound action potentials in the frog sciatic nerve

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Matsushita, Akitomo; Ohtsubo, Sena; Fujita, Tsugumi

    Highlights: •TRPA1 agonists inhibited compound action potentials in frog sciatic nerves. •This inhibition was not mediated by TRPA1 channels. •This efficacy was comparable to those of lidocaine and cocaine. •We found for the first time an ability of TRPA1 agonists to inhibit nerve conduction. -- Abstract: Although TRPV1 and TRPM8 agonists (vanilloid capsaicin and menthol, respectively) at high concentrations inhibit action potential conduction, it remains to be unknown whether TRPA1 agonists have a similar action. The present study examined the actions of TRPA1 agonists, cinnamaldehyde (CA) and allyl isothiocyanate (AITC), which differ in chemical structure from each other, on compoundmore » action potentials (CAPs) recorded from the frog sciatic nerve by using the air-gap method. CA and AITC concentration-dependently reduced the peak amplitude of the CAP with the IC{sub 50} values of 1.2 and 1.5 mM, respectively; these activities were resistant to a non-selective TRP antagonist ruthenium red or a selective TRPA1 antagonist HC-030031. The CA and AITC actions were distinct in property; the latter but not former action was delayed in onset and partially reversible, and CA but not AITC increased thresholds to elicit CAPs. A CAP inhibition was seen by hydroxy-α-sanshool (by 60% at 0.05 mM), which activates both TRPA1 and TRPV1 channels, a non-vanilloid TRPV1 agonist piperine (by 20% at 0.07 mM) and tetrahydrolavandulol (where the six-membered ring of menthol is opened; IC{sub 50} = 0.38 mM). It is suggested that TRPA1 agonists as well as TRPV1 and TRPM8 agonists have an ability to inhibit nerve conduction without TRP activation, although their agonists are quite different in chemical structure from each other.« less

  1. DBI potential, DBI inflation action and general Lagrangian relative to phantom, K-essence and quintessence

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Zhang, Qing; Huang, Yong-Chang, E-mail: ychuang@bjut.edu.cn

    We derive a Dirac-Born-Infeld (DBI) potential and DBI inflation action by rescaling the metric. The determinant of the induced metric naturally includes the kinetic energy and the potential energy. In particular, the potential energy and kinetic energy can convert into each other in any order, which is in agreement with the limit of classical physics. This is quite different from the usual DBI action. We show that the Taylor expansion of the DBI action can be reduced into the form in the non-linear classical physics. These investigations are the support for the statement that the results of string theory aremore » consistent with quantum mechanics and classical physics. We deduce the Phantom, K-essence, Quintessence and Generalized Klein-Gordon Equation from the DBI model.« less

  2. The dependence of the action potential of the frog's heart on the external and intracellular sodium concentration

    PubMed Central

    Niedergerke, R.; Orkand, R. K.

    1966-01-01

    1. The overshoot of the action potential of the frog's heart was reduced when external sodium chloride was replaced by sucrose. However, the potential decrement was only 17·3 mV for a 10-fold reduction of sodium as compared with 58 mV expected on the basis of the sodium hypothesis of excitation. 2. Replacement of up to 75% of the external sodium by choline did not reduce the overshoot, provided atropine was present in sufficient concentrations to suppress any parasympathomimetic action. 3. The maximum rate of rise of the action potential markedly declined in low sodium fluids whether sucrose or choline chloride was used to replace sodium chloride. 4. The maximum rate of rise was reduced to only a small extent when external sodium was replaced by lithium. 5. Increasing the intracellular sodium concentration in exchange for lost potassium caused overshoots to decline. The effects resembled those obtained in similar experiments with skeletal muscle fibres (Desmedt, 1953). 6. Action potentials occurring under certain conditions even in the presence of very low external sodium concentrations (≤ 5% normal) also declined in height when the intracellular sodium concentration was increased. 7. The behaviour of the action potential in low external sodium concentrations may be explained by an action of calcium on the excitable membrane. PMID:5921833

  3. Modulation of hERG potassium channel gating normalizes action potential duration prolonged by dysfunctional KCNQ1 potassium channel

    PubMed Central

    Zhang, Hongkang; Zou, Beiyan; Yu, Haibo; Moretti, Alessandra; Wang, Xiaoying; Yan, Wei; Babcock, Joseph J.; Bellin, Milena; McManus, Owen B.; Tomaselli, Gordon; Nan, Fajun; Laugwitz, Karl-Ludwig; Li, Min

    2012-01-01

    Long QT syndrome (LQTS) is a genetic disease characterized by a prolonged QT interval in an electrocardiogram (ECG), leading to higher risk of sudden cardiac death. Among the 12 identified genes causal to heritable LQTS, ∼90% of affected individuals harbor mutations in either KCNQ1 or human ether-a-go-go related genes (hERG), which encode two repolarizing potassium currents known as IKs and IKr. The ability to quantitatively assess contributions of different current components is therefore important for investigating disease phenotypes and testing effectiveness of pharmacological modulation. Here we report a quantitative analysis by simulating cardiac action potentials of cultured human cardiomyocytes to match the experimental waveforms of both healthy control and LQT syndrome type 1 (LQT1) action potentials. The quantitative evaluation suggests that elevation of IKr by reducing voltage sensitivity of inactivation, not via slowing of deactivation, could more effectively restore normal QT duration if IKs is reduced. Using a unique specific chemical activator for IKr that has a primary effect of causing a right shift of V1/2 for inactivation, we then examined the duration changes of autonomous action potentials from differentiated human cardiomyocytes. Indeed, this activator causes dose-dependent shortening of the action potential durations and is able to normalize action potentials of cells of patients with LQT1. In contrast, an IKr chemical activator of primary effects in slowing channel deactivation was not effective in modulating action potential durations. Our studies provide both the theoretical basis and experimental support for compensatory normalization of action potential duration by a pharmacological agent. PMID:22745159

  4. ER Stress-Mediated Signaling: Action Potential and Ca(2+) as Key Players.

    PubMed

    Bahar, Entaz; Kim, Hyongsuk; Yoon, Hyonok

    2016-09-15

    The proper functioning of the endoplasmic reticulum (ER) is crucial for multiple cellular activities and survival. Disturbances in the normal ER functions lead to the accumulation and aggregation of unfolded proteins, which initiates an adaptive response, the unfolded protein response (UPR), in order to regain normal ER functions. Failure to activate the adaptive response initiates the process of programmed cell death or apoptosis. Apoptosis plays an important role in cell elimination, which is essential for embryogenesis, development, and tissue homeostasis. Impaired apoptosis can lead to the development of various pathological conditions, such as neurodegenerative and autoimmune diseases, cancer, or acquired immune deficiency syndrome (AIDS). Calcium (Ca(2+)) is one of the key regulators of cell survival and it can induce ER stress-mediated apoptosis in response to various conditions. Ca(2+) regulates cell death both at the early and late stages of apoptosis. Severe Ca(2+) dysregulation can promote cell death through apoptosis. Action potential, an electrical signal transmitted along the neurons and muscle fibers, is important for conveying information to, from, and within the brain. Upon the initiation of the action potential, increased levels of cytosolic Ca(2+) (depolarization) lead to the activation of the ER stress response involved in the initiation of apoptosis. In this review, we discuss the involvement of Ca(2+) and action potential in ER stress-mediated apoptosis.

  5. Antibacterial free fatty acids: activities, mechanisms of action and biotechnological potential.

    PubMed

    Desbois, Andrew P; Smith, Valerie J

    2010-02-01

    Amongst the diverse and potent biological activities of free fatty acids (FFAs) is the ability to kill or inhibit the growth of bacteria. The antibacterial properties of FFAs are used by many organisms to defend against parasitic or pathogenic bacteria. Whilst their antibacterial mode of action is still poorly understood, the prime target of FFA action is the cell membrane, where FFAs disrupt the electron transport chain and oxidative phosphorylation. Besides interfering with cellular energy production, FFA action may also result from the inhibition of enzyme activity, impairment of nutrient uptake, generation of peroxidation and auto-oxidation degradation products or direct lysis of bacterial cells. Their broad spectrum of activity, non-specific mode of action and safety makes them attractive as antibacterial agents for various applications in medicine, agriculture and food preservation, especially where the use of conventional antibiotics is undesirable or prohibited. Moreover, the evolution of inducible FFA-resistant phenotypes is less problematic than with conventional antibiotics. The potential for commercial or biomedical exploitation of antibacterial FFAs, especially for those from natural sources, is discussed.

  6. Configuration Management and Infrastructure Monitoring Using CFEngine and Icinga for Real-time Heterogeneous Data Taking Environment

    NASA Astrophysics Data System (ADS)

    Poat, M. D.; Lauret, J.; Betts, W.

    2015-12-01

    The STAR online computing environment is an intensive ever-growing system used for real-time data collection and analysis. Composed of heterogeneous and sometimes groups of custom-tuned machines, the computing infrastructure was previously managed by manual configurations and inconsistently monitored by a combination of tools. This situation led to configuration inconsistency and an overload of repetitive tasks along with lackluster communication between personnel and machines. Globally securing this heterogeneous cyberinfrastructure was tedious at best and an agile, policy-driven system ensuring consistency, was pursued. Three configuration management tools, Chef, Puppet, and CFEngine have been compared in reliability, versatility and performance along with a comparison of infrastructure monitoring tools Nagios and Icinga. STAR has selected the CFEngine configuration management tool and the Icinga infrastructure monitoring system leading to a versatile and sustainable solution. By leveraging these two tools STAR can now swiftly upgrade and modify the environment to its needs with ease as well as promptly react to cyber-security requests. By creating a sustainable long term monitoring solution, the detection of failures was reduced from days to minutes, allowing rapid actions before the issues become dire problems, potentially causing loss of precious experimental data or uptime.

  7. Transmural Ultrasound-based Visualization of Patterns of Action Potential Wave Propagation in Cardiac Tissue

    PubMed Central

    Luther, Stefan; Singh, Rupinder; Gilmour, Robert F.

    2010-01-01

    The pattern of action potential propagation during various tachyarrhythmias is strongly suspected to be composed of multiple re-entrant waves, but has never been imaged in detail deep within myocardial tissue. An understanding of the nature and dynamics of these waves is important in the development of appropriate electrical or pharmacological treatments for these pathological conditions. We propose a new imaging modality that uses ultrasound to visualize the patterns of propagation of these waves through the mechanical deformations they induce. The new method would have the distinct advantage of being able to visualize these waves deep within cardiac tissue. In this article, we describe one step that would be necessary in this imaging process—the conversion of these deformations into the action potential induced active stresses that produced them. We demonstrate that, because the active stress induced by an action potential is, to a good approximation, only nonzero along the local fiber direction, the problem in our case is actually overdetermined, allowing us to obtain a complete solution. Use of two- rather than three-dimensional displacement data, noise in these displacements, and/or errors in the measurements of the fiber orientations all produce substantial but acceptable errors in the solution. We conclude that the reconstruction of action potential-induced active stress from the deformation it causes appears possible, and that, therefore, the path is open to the development of the new imaging modality. PMID:20499183

  8. Amphetamine elevates nucleus accumbens dopamine via an action potential-dependent mechanism that is modulated by endocannabinoids

    PubMed Central

    Covey, Dan P.; Bunner, Kendra D.; Schuweiler, Douglas R.; Cheer, Joseph F.; Garris, Paul A.

    2018-01-01

    The reinforcing effects of abused drugs are mediated by their ability to elevate nucleus accumbens dopamine. Amphetamine (AMPH) was historically thought to increase dopamine by an action potential-independent, non-exocytotic type of release called efflux, involving reversal of dopamine transporter function and driven by vesicular dopamine depletion. Growing evidence suggests that AMPH also acts by an action potential-dependent mechanism. Indeed, fast-scan cyclic voltammetry demonstrates that AMPH activates dopamine transients, reward-related phasic signals generated by burst firing of dopamine neurons and dependent on intact vesicular dopamine. Not established for AMPH but indicating a shared mechanism, endocannabinoids facilitate this activation of dopamine transients by broad classes of abused drugs. Here, using fast-scan cyclic voltammetry coupled to pharmacological manipulations in awake rats, we investigated the action potential and endocannabinoid dependence of AMPH-induced elevations in nucleus accumbens dopamine. AMPH increased the frequency, amplitude and duration of transients, which were observed riding on top of slower dopamine increases. Surprisingly, silencing dopamine neuron firing abolished all AMPH-induced dopamine elevations, identifying an action potential-dependent origin. Blocking cannabinoid type 1 receptors prevented AMPH from increasing transient frequency, similar to reported effects on other abused drugs, but not from increasing transient duration and inhibiting dopamine uptake. Thus, AMPH elevates nucleus accumbens dopamine by eliciting transients via cannabinoid type 1 receptors and promoting the summation of temporally coincident transients, made more numerous, larger and wider by AMPH. Collectively, these findings are inconsistent with AMPH eliciting action potential-independent dopamine efflux and vesicular dopamine depletion, and support endocannabinoids facilitating phasic dopamine signalling as a common action in drug reinforcement

  9. Amphetamine elevates nucleus accumbens dopamine via an action potential-dependent mechanism that is modulated by endocannabinoids.

    PubMed

    Covey, Dan P; Bunner, Kendra D; Schuweiler, Douglas R; Cheer, Joseph F; Garris, Paul A

    2016-06-01

    The reinforcing effects of abused drugs are mediated by their ability to elevate nucleus accumbens dopamine. Amphetamine (AMPH) was historically thought to increase dopamine by an action potential-independent, non-exocytotic type of release called efflux, involving reversal of dopamine transporter function and driven by vesicular dopamine depletion. Growing evidence suggests that AMPH also acts by an action potential-dependent mechanism. Indeed, fast-scan cyclic voltammetry demonstrates that AMPH activates dopamine transients, reward-related phasic signals generated by burst firing of dopamine neurons and dependent on intact vesicular dopamine. Not established for AMPH but indicating a shared mechanism, endocannabinoids facilitate this activation of dopamine transients by broad classes of abused drugs. Here, using fast-scan cyclic voltammetry coupled to pharmacological manipulations in awake rats, we investigated the action potential and endocannabinoid dependence of AMPH-induced elevations in nucleus accumbens dopamine. AMPH increased the frequency, amplitude and duration of transients, which were observed riding on top of slower dopamine increases. Surprisingly, silencing dopamine neuron firing abolished all AMPH-induced dopamine elevations, identifying an action potential-dependent origin. Blocking cannabinoid type 1 receptors prevented AMPH from increasing transient frequency, similar to reported effects on other abused drugs, but not from increasing transient duration and inhibiting dopamine uptake. Thus, AMPH elevates nucleus accumbens dopamine by eliciting transients via cannabinoid type 1 receptors and promoting the summation of temporally coincident transients, made more numerous, larger and wider by AMPH. Collectively, these findings are inconsistent with AMPH eliciting action potential-independent dopamine efflux and vesicular dopamine depletion, and support endocannabinoids facilitating phasic dopamine signalling as a common action in drug reinforcement

  10. Identity configurations: a new perspective on identity formation in contemporary society.

    PubMed

    Schachter, Elli P

    2004-02-01

    This paper deals with the theoretical construct of "identity configuration." It portrays the different possible ways in which individuals configure the relationship among potentially conflicting identifications in the process of identity formation. In order to explicate these configurations, I analyzed narratives of identity development retold by individuals describing personal identity conflicts that arise within a larger context of sociocultural conflict. Thirty Jewish modern orthodox young adults were interviewed regarding a potentially conflictual identity issue (i.e. their religious and sexual development). Their deliberations, as described in the interviews, were examined, and four different configurations were identified: a configuration based on choice and suppression; an assimilative and synthesizing configuration; a confederacy of identifications; and a configuration based on the thrill of dissonance. The different configurations are illustrated through exemplars, and the possible implications of the concept of "configuration" for identity theory are discussed.

  11. Back-Propagation of Physiological Action Potential Output in Dendrites of Slender-Tufted L5A Pyramidal Neurons

    PubMed Central

    Grewe, Benjamin F.; Bonnan, Audrey; Frick, Andreas

    2009-01-01

    Pyramidal neurons of layer 5A are a major neocortical output type and clearly distinguished from layer 5B pyramidal neurons with respect to morphology, in vivo firing patterns, and connectivity; yet knowledge of their dendritic properties is scant. We used a combination of whole-cell recordings and Ca2+ imaging techniques in vitro to explore the specific dendritic signaling role of physiological action potential patterns recorded in vivo in layer 5A pyramidal neurons of the whisker-related ‘barrel cortex’. Our data provide evidence that the temporal structure of physiological action potential patterns is crucial for an effective invasion of the main apical dendrites up to the major branch point. Both the critical frequency enabling action potential trains to invade efficiently and the dendritic calcium profile changed during postnatal development. In contrast to the main apical dendrite, the more passive properties of the short basal and apical tuft dendrites prevented an efficient back-propagation. Various Ca2+ channel types contributed to the enhanced calcium signals during high-frequency firing activity, whereas A-type K+ and BKCa channels strongly suppressed it. Our data support models in which the interaction of synaptic input with action potential output is a function of the timing, rate and pattern of action potentials, and dendritic location. PMID:20508744

  12. Low concentrations of procaine and diethylaminoethanol reduce the excitability but not the action potential amplitude of hippocampal pyramidal cells.

    PubMed

    Butterworth, J F; Cole, L R

    1990-10-01

    To determine whether concentrations of diethylaminoethanol (DEAE) and procaine below those that reduce the amplitude of action potentials might alter the excitability of brain cells, a single microelectrode intracellular recording technique was used to measure firing threshold and action potential amplitude of pyramidal cells in rat hippocampal slices. At low concentrations of both DEAE (less than or equal to 5 mM) and procaine (less than or equal to 0.5 mM), firing threshold was significantly increased (P less than 0.01), whereas action potential spike amplitude was minimally altered. At higher concentrations, both drugs significantly decreased action potential spike amplitude (P less than 0.025) as well as increased firing threshold (P less than 0.001). Diethylaminoethanol tended to increase threshold relatively more than procaine, when drug concentrations that similarly reduced action potential amplitude were compared. All actions of DEAE and procaine were reversible. Inhibition of action potentials by DEAE and procaine was clearly concentration-dependent (P less than or equal to 0.015). Diethylaminoethanol effects on threshold were marginally concentration-dependent (P = 0.08); procaine did not demonstrate clear concentration-dependent effects (P = 0.33) over the concentrations tested in this study. These similar actions of procaine and DEAE on brain cells suggest a mechanism by which intravenous local anesthetics may contribute to the general anesthetic state. Moreover, it appears possible that procaine metabolism and DEAE accumulation may underlie the prolonged effects sometimes seen after intravenous procaine administration.

  13. Rapid Ca2+ flux through the transverse tubular membrane, activated by individual action potentials in mammalian skeletal muscle

    PubMed Central

    Launikonis, Bradley S; Stephenson, D George; Friedrich, Oliver

    2009-01-01

    Periods of low frequency stimulation are known to increase the net Ca2+ uptake in skeletal muscle but the mechanism responsible for this Ca2+ entry is not known. In this study a novel high-resolution fluorescence microscopy approach allowed the detection of an action potential-induced Ca2+ flux across the tubular (t-) system of rat extensor digitorum longus muscle fibres that appears to be responsible for the net uptake of Ca2+ in working muscle. Action potentials were triggered in the t-system of mechanically skinned fibres from rat by brief field stimulation and t-system [Ca2+] ([Ca2+]t-sys) and cytoplasmic [Ca2+] ([Ca2+]cyto) were simultaneously resolved on a confocal microscope. When initial [Ca2+]t-sys was ≥ 0.2 mm a Ca2+ flux from t-system to the cytoplasm was observed following a single action potential. The action potential-induced Ca2+ flux and associated t-system Ca2+ permeability decayed exponentially and displayed inactivation characteristics such that further Ca2+ entry across the t-system could not be observed after 2–3 action potentials at 10 Hz stimulation rate. When [Ca2+]t-sys was closer to 0.1 mm, a transient rise in [Ca2+]t-sys was observed almost concurrently with the increase in [Ca2+]cyto following the action potential. The change in direction of Ca2+ flux was consistent with changes in the direction of the driving force for Ca2+. This is the first demonstration of a rapid t-system Ca2+ flux associated with a single action potential in mammalian skeletal muscle. The properties of this channel are inconsistent with a flux through the L-type Ca2+ channel suggesting that an as yet unidentified t-system protein is conducting this current. This action potential-activated Ca2+ flux provides an explanation for the previously described Ca2+ entry and accumulation observed with prolonged, intermittent muscle activity. PMID:19332499

  14. Non-potential Field Formation in the X-shaped Quadrupole Magnetic Field Configuration

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kawabata, Y.; Shimizu, T.; Inoue, S., E-mail: kawabata.yusuke@ac.jaxa.jp

    Some types of solar flares are observed in X-shaped quadrupolar field configuration. To understand the magnetic energy storage in such a region, we studied non-potential field formation in an X-shaped quadrupolar field region formed in the active region NOAA 11967, which produced three X-shaped M-class flares on 2014 February 2. Nonlinear force-free field modeling was applied to a time series of vector magnetic field maps from the Solar Optical Telescope on board Hinode and the Helioseismic and Magnetic Imager on board the Solar Dynamics Observatory . Our analysis of the temporal three-dimensional magnetic field evolution shows that the sufficient freemore » energy had already been stored more than 10 hr before the occurrence of the first M-class flare and that the storage was observed in a localized region. In this localized region, quasi-separatrix layers (QSLs) started to develop gradually from 9 hr before the first M-class flare. One of the flare ribbons that appeared in the first M-class flare was co-spatial with the location of the QSLs, suggesting that the formation of the QSLs is important in the process of energy release. These QSLs do not appear in the potential field calculation, indicating that they were created by the non-potential field. The formation of the QSLs was associated with the transverse photospheric motion of the pre-emerged flux and the emergence of a new flux. This observation indicates that the occurrence of the flares requires the formation of QSLs in the non-potential field in which free magnetic energy is stored in advance.« less

  15. Improved outcomes in auditory brainstem implantation with the use of near-field electrical compound action potentials.

    PubMed

    Mandalà, Marco; Colletti, Liliana; Colletti, Giacomo; Colletti, Vittorio

    2014-12-01

    To compare the outcomes (auditory threshold and open-set speech perception at 48-month follow-up) of a new near-field monitoring procedure, electrical compound action potential, on positioning the auditory brainstem implant electrode array on the surface of the cochlear nuclei versus the traditional far-field electrical auditory brainstem response. Retrospective study. Tertiary referral center. Among the 202 patients with auditory brainstem implants fitted and monitored with electrical auditory brainstem response during implant fitting, 9 also underwent electrical compound action potential recording. These subjects were matched retrospectively with a control group of 9 patients in whom only the electrical auditory brainstem response was recorded. Electrical compound action potentials were obtained using a cotton-wick recording electrode located near the surface of the cochlear nuclei and on several cranial nerves. Significantly lower potential thresholds were observed with the recording electrode located on the cochlear nuclei surface compared with the electrical auditory brainstem response (104.4 ± 32.5 vs 158.9 ± 24.2, P = .0030). Electrical brainstem response and compound action potentials identified effects on the neighboring cranial nerves on 3.2 ± 2.4 and 7.8 ± 3.2 electrodes, respectively (P = .0034). Open-set speech perception outcomes at 48-month follow-up had improved significantly in the near- versus far-field recording groups (78.9% versus 56.7%; P = .0051). Electrical compound action potentials during auditory brainstem implantation significantly improved the definition of the potential threshold and the number of auditory and extra-auditory waves generated. It led to the best coupling between the electrode array and cochlear nuclei, significantly improving the overall open-set speech perception. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2014.

  16. Dynamic Action Potential Restitution Contributes to Mechanical Restitution in Right Ventricular Myocytes From Pulmonary Hypertensive Rats.

    PubMed

    Hardy, Matthew E L; Pervolaraki, Eleftheria; Bernus, Olivier; White, Ed

    2018-01-01

    We investigated the steepened dynamic action potential duration (APD) restitution of rats with pulmonary artery hypertension (PAH) and right ventricular (RV) failure and tested whether the observed APD restitution properties were responsible for negative mechanical restitution in these myocytes. PAH and RV failure were provoked in male Wistar rats by a single injection of monocrotaline (MCT) and compared with saline-injected animals (CON). Action potentials were recorded from isolated RV myocytes at stimulation frequencies between 1 and 9 Hz. Action potential waveforms recorded at 1 Hz were used as voltage clamp profiles (action potential clamp) at stimulation frequencies between 1 and 7 Hz to evoke rate-dependent currents. Voltage clamp profiles mimicking typical CON and MCT APD restitution were applied and cell shortening simultaneously monitored. Compared with CON myocytes, MCT myocytes were hypertrophied; had less polarized diastolic membrane potentials; had action potentials that were triggered by decreased positive current density and shortened by decreased negative current density; APD was longer and APD restitution steeper. APD90 restitution was unchanged by exposure to the late Na + -channel blocker (5 μM) ranolazine or the intracellular Ca 2+ buffer BAPTA. Under AP clamp, stimulation frequency-dependent inward currents were smaller in MCT myocytes and were abolished by BAPTA. In MCT myocytes, increasing stimulation frequency decreased contraction amplitude when depolarization duration was shortened, to mimic APD restitution, but not when depolarization duration was maintained. We present new evidence that the membrane potential of PAH myocytes is less stable than normal myocytes, being more easily perturbed by external currents. These observations can explain increased susceptibility to arrhythmias. We also present novel evidence that negative APD restitution is at least in part responsible for the negative mechanical restitution in PAH myocytes. Thus

  17. Sensitivity to structure in action sequences: An infant event-related potential study.

    PubMed

    Monroy, Claire D; Gerson, Sarah A; Domínguez-Martínez, Estefanía; Kaduk, Katharina; Hunnius, Sabine; Reid, Vincent

    2017-05-06

    Infants are sensitive to structure and patterns within continuous streams of sensory input. This sensitivity relies on statistical learning, the ability to detect predictable regularities in spatial and temporal sequences. Recent evidence has shown that infants can detect statistical regularities in action sequences they observe, but little is known about the neural process that give rise to this ability. In the current experiment, we combined electroencephalography (EEG) with eye-tracking to identify electrophysiological markers that indicate whether 8-11-month-old infants detect violations to learned regularities in action sequences, and to relate these markers to behavioral measures of anticipation during learning. In a learning phase, infants observed an actor performing a sequence featuring two deterministic pairs embedded within an otherwise random sequence. Thus, the first action of each pair was predictive of what would occur next. One of the pairs caused an action-effect, whereas the second did not. In a subsequent test phase, infants observed another sequence that included deviant pairs, violating the previously observed action pairs. Event-related potential (ERP) responses were analyzed and compared between the deviant and the original action pairs. Findings reveal that infants demonstrated a greater Negative central (Nc) ERP response to the deviant actions for the pair that caused the action-effect, which was consistent with their visual anticipations during the learning phase. Findings are discussed in terms of the neural and behavioral processes underlying perception and learning of structured action sequences. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Low K+-induced hyperpolarizations trigger transient depolarizations and action potentials in rabbit ventricular myocytes

    PubMed Central

    Akuzawa-Tateyama, M; Tateyama, M; Ochi, R

    1998-01-01

    The effects of large reductions of [K+]o on membrane potential were studied in isolated rabbit ventricular myocytes using the whole-cell patch clamp technique.Decreasing [K+]o from the normal level of 5.4 mm to 0.1 mm increased resting membrane potential (Vrest) from −75.6 ± 0.3 to −140.3 ± 1.9 mV (means ± s.e.m; n = 127), induced irregular, transient depolarizations with mean maximal amplitudes of 19.5 ± 1.5 mV and elicited action potentials in 56.7 % of trials. The action potentials exhibited overshoots of 37.9 ± 1.5 mV (n = 72) and sustained plateaux.Addition of 0.1 mm La3+ in the presence of 0.1 mm[K+]o significantly increased Vrest but decreased the amplitude of transient depolarizations and suppressed the firing of action potentials.Replacement of external Na+ or Cl− with N-methyl-D-glucamine or aspartate, respectively, or internal dialysis with 10 mm EGTA or BAPTA had little effect on low [K+]o-induced membrane potential changes.Hyperpolarizing voltage clamp pulses to potentials between −110 and −200 mV activated irregular inward currents that increased in amplitude and frequency with increasing hyperpolarization and were depressed by 0.1 mm La3+.The generation of transient depolarizations by low [K+]o can be explained as being a consequence of decreasing the inward rectifier K+ current (IK1) and the appearance of inward currents reflecting electroporation resulting from strong electric fields across the membrane. PMID:9824717

  19. The optimal distance between two electrode tips during recording of compound nerve action potentials in the rat median nerve

    PubMed Central

    Li, Yongping; Lao, Jie; Zhao, Xin; Tian, Dong; Zhu, Yi; Wei, Xiaochun

    2014-01-01

    The distance between the two electrode tips can greatly influence the parameters used for recording compound nerve action potentials. To investigate the optimal parameters for these recordings in the rat median nerve, we dissociated the nerve using different methods and compound nerve action potentials were orthodromically or antidromically recorded with different electrode spacings. Compound nerve action potentials could be consistently recorded using a method in which the middle part of the median nerve was intact, with both ends dissociated from the surrounding fascia and a ground wire inserted into the muscle close to the intact part. When the distance between two stimulating electrode tips was increased, the threshold and supramaximal stimulating intensity of compound nerve action potentials were gradually decreased, but the amplitude was not changed significantly. When the distance between two recording electrode tips was increased, the amplitude was gradually increased, but the threshold and supramaximal stimulating intensity exhibited no significant change. Different distances between recording and stimulating sites did not produce significant effects on the aforementioned parameters. A distance of 5 mm between recording and stimulating electrodes and a distance of 10 mm between recording and stimulating sites were found to be optimal for compound nerve action potential recording in the rat median nerve. In addition, the orthodromic compound action potential, with a biphasic waveform that was more stable and displayed less interference (however also required a higher threshold and higher supramaximal stimulus), was found to be superior to the antidromic compound action potential. PMID:25206798

  20. An exploratory study of organization design configurations in health care delivery organizations.

    PubMed

    Sheppeck, Mick; Militello, Jack

    2014-01-01

    Organizations are configurations of variables that support each other to achieve customer satisfaction. Based on Treacy and Wiersema (1995), we predicted the emergence of two configurations, one supporting a product leadership stance and one predicting the customer intimate approach from a set of 73 for profit health care clinics. In addition, we predicted the emergence of a configuration where the scores on most variables were near the mean for each variable. Using cluster analysis and discriminant function analysis, we identified three configurations: one a "master of two" strategy, one "stuck-in-the-middle," and one showing scores well below the mean on most variables. The implications for organization design and manager actions in the health care industry are discussed.

  1. Central Nervous System-Toxic Lidocaine Concentrations Unmask L-Type Ca²⁺ Current-Mediated Action Potentials in Rat Thalamocortical Neurons: An In Vitro Mechanism of Action Study.

    PubMed

    Putrenko, Igor; Ghavanini, Amer A; Meyer Schöniger, Katrin S; Schwarz, Stephan K W

    2016-05-01

    High systemic lidocaine concentrations exert well-known toxic effects on the central nervous system (CNS), including seizures, coma, and death. The underlying mechanisms are still largely obscure, and the actions of lidocaine on supraspinal neurons have received comparatively little study. We recently found that lidocaine at clinically neurotoxic concentrations increases excitability mediated by Na-independent, high-threshold (HT) action potential spikes in rat thalamocortical neurons. Our goal in this study was to characterize these spikes and test the hypothesis that they are generated by HT Ca currents, previously implicated in neurotoxicity. We also sought to identify and isolate the specific underlying subtype of Ca current. We investigated the actions of lidocaine in the CNS-toxic concentration range (100 μM-1 mM) on ventrobasal thalamocortical neurons in rat brain slices in vitro, using whole-cell patch-clamp recordings aided by differential interference contrast infrared videomicroscopy. Drugs were bath applied; action potentials were generated using current clamp protocols, and underlying currents were identified and isolated with ion channel blockers and electrolyte substitution. Lidocaine (100 μM-1 mM) abolished Na-dependent tonic firing in all neurons tested (n = 46). However, in 39 of 46 (85%) neurons, lidocaine unmasked evoked HT action potentials with lower amplitudes and rates of de-/repolarization compared with control. These HT action potentials remained during the application of tetrodotoxin (600 nM), were blocked by Cd (50 μM), and disappeared after superfusion with an extracellular solution deprived of Ca. These features implied that the unmasked potentials were generated by high-voltage-activated Ca channels and not by Na channels. Application of the L-type Ca channel blocker, nifedipine (5 μM), completely blocked the HT potentials, whereas the N-type Ca channel blocker, ω-conotoxin GVIA (1 μM), had little effect. At clinically CNS

  2. Activation of Mechanosensitive Transient Receptor Potential/Piezo Channels in Odontoblasts Generates Action Potentials in Cocultured Isolectin B4-negative Medium-sized Trigeminal Ganglion Neurons.

    PubMed

    Sato, Masaki; Ogura, Kazuhiro; Kimura, Maki; Nishi, Koichi; Ando, Masayuki; Tazaki, Masakazu; Shibukawa, Yoshiyuki

    2018-06-01

    Various stimuli to the dentin surface elicit dentinal pain by inducing dentinal fluid movement causing cellular deformation in odontoblasts. Although odontoblasts detect deformation by the activation of mechanosensitive ionic channels, it is still unclear whether odontoblasts are capable of establishing neurotransmission with myelinated A delta (Aδ) neurons. Additionally, it is still unclear whether these neurons evoke action potentials by neurotransmitters from odontoblasts to mediate sensory transduction in dentin. Thus, we investigated evoked inward currents and evoked action potentials form trigeminal ganglion (TG) neurons after odontoblast mechanical stimulation. We used patch clamp recordings to identify electrophysiological properties and record evoked responses in TG neurons. We classified TG cells into small-sized and medium-sized neurons. In both types of neurons, we observed voltage-dependent inward currents. The currents from medium-sized neurons showed fast inactivation kinetics. When mechanical stimuli were applied to odontoblasts, evoked inward currents were recorded from medium-sized neurons. Antagonists for the ionotropic adenosine triphosphate receptor (P2X 3 ), transient receptor potential channel subfamilies, and Piezo1 channel significantly inhibited these inward currents. Mechanical stimulation to odontoblasts also generated action potentials in the isolectin B 4 -negative medium-sized neurons. Action potentials in these isolectin B 4 -negative medium-sized neurons showed a short duration. Overall, electrophysiological properties of neurons indicate that the TG neurons with recorded evoked responses after odontoblast mechanical stimulation were myelinated Aδ neurons. Odontoblasts established neurotransmission with myelinated Aδ neurons via P2X 3 receptor activation. The results also indicated that mechanosensitive TRP/Piezo1 channels were functionally expressed in odontoblasts. The activation of P2X 3 receptors induced an action potential

  3. Novel cinnamic acid/4-aminoquinoline conjugates bearing non-proteinogenic amino acids: towards the development of potential dual action antimalarials.

    PubMed

    Pérez, Bianca C; Teixeira, Cátia; Figueiras, Marta; Gut, Jiri; Rosenthal, Philip J; Gomes, José R B; Gomes, Paula

    2012-08-01

    A series of cinnamic acid/4-aminoquinoline conjugates conceived to link, through a proper retro-enantio dipeptide, a heterocyclic core known to prevent hemozoin formation, to a trans-cinnamic acid motif capable of inhibiting enzyme catalytic Cys residues, were synthesized as potential dual-action antimalarials. The effect of amino acid configuration and the absence of the dipeptide spacer were also assessed. The replacement of the D-amino acids by their natural L counterparts led to a decrease in both anti-plasmodial and falcipain-inhibitory activity, suggesting that the former are preferable. Molecules with such spacer were active against blood-stage Plasmodium falciparum, in vitro, and hemozoin formation, implying that the dipeptide has a key role in mediating these two activities. In turn, compounds without spacer were better falcipain-2 inhibitors, likely because these compounds are smaller and have their vinyl bonds in closer vicinity to the catalytic Cys, as suggested by molecular modeling calculations. These novel conjugates constitute promising leads for the development of new antiplasmodials targeted at blood-stage malaria parasites. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  4. Fixed-node diffusion Monte Carlo potential energy curve of the fluorine molecule F{sub 2} using selected configuration interaction trial wavefunctions

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Giner, Emmanuel; Scemama, Anthony; Caffarel, Michel

    2015-01-28

    The potential energy curve of the F{sub 2} molecule is calculated with Fixed-Node Diffusion Monte Carlo (FN-DMC) using Configuration Interaction (CI)-type trial wavefunctions. To keep the number of determinants reasonable and thus make FN-DMC calculations feasible in practice, the CI expansion is restricted to those determinants that contribute the most to the total energy. The selection of the determinants is made using the CIPSI approach (Configuration Interaction using a Perturbative Selection made Iteratively). The trial wavefunction used in FN-DMC is directly issued from the deterministic CI program; no Jastrow factor is used and no preliminary multi-parameter stochastic optimization of themore » trial wavefunction is performed. The nodes of CIPSI wavefunctions are found to reduce significantly the fixed-node error and to be systematically improved upon increasing the number of selected determinants. To reduce the non-parallelism error of the potential energy curve, a scheme based on the use of a R-dependent number of determinants is introduced. Using Dunning’s cc-pVDZ basis set, the FN-DMC energy curve of F{sub 2} is found to be of a quality similar to that obtained with full configuration interaction/cc-pVQZ.« less

  5. Action-minimizing solutions of the one-dimensional N-body problem

    NASA Astrophysics Data System (ADS)

    Yu, Xiang; Zhang, Shiqing

    2018-05-01

    We supplement the following result of C. Marchal on the Newtonian N-body problem: A path minimizing the Lagrangian action functional between two given configurations is always a true (collision-free) solution when the dimension d of the physical space R^d satisfies d≥2. The focus of this paper is on the fixed-ends problem for the one-dimensional Newtonian N-body problem. We prove that a path minimizing the action functional in the set of paths joining two given configurations and having all the time the same order is always a true (collision-free) solution. Considering the one-dimensional N-body problem with equal masses, we prove that (i) collision instants are isolated for a path minimizing the action functional between two given configurations, (ii) if the particles at two endpoints have the same order, then the path minimizing the action functional is always a true (collision-free) solution and (iii) when the particles at two endpoints have different order, although there must be collisions for any path, we can prove that there are at most N! - 1 collisions for any action-minimizing path.

  6. Activity-dependent modulation of the axonal conduction of action potentials along rat hippocampal mossy fibers.

    PubMed

    Chida, Kuniaki; Kaneko, Kenya; Fujii, Satoshi; Yamazaki, Yoshihiko

    2015-01-01

    The axonal conduction of action potentials in the nervous system is generally considered to be a stable signal for the relaying of information, and its dysfunction is involved in impairment of cognitive function. Recent evidence suggests that the conduction properties and excitability of axons are more variable than traditionally thought. To investigate possible changes in the conduction of action potentials along axons in the central nervous system, we recorded action potentials from granule cells that were evoked and conducted antidromically along unmyelinated mossy fibers in the rat hippocampus. To evaluate changes in axons by eliminating any involvement of changes in the somata, two latency values were obtained by stimulating at two different positions and the latency difference between the action potentials was measured. A conditioning electrical stimulus of 20 pulses at 1 Hz increased the latency difference and this effect, which lasted for approximately 30 s, was inhibited by the application of an α-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA)/kainate receptor antagonist or a GluK1-containing kainate receptor antagonist, but not by an AMPA receptor-selective antagonist or an N-methyl-d-aspartate receptor antagonist. These results indicated that axonal conduction in mossy fibers is modulated in an activity-dependent manner through the activation of GluK1-containing kainate receptors. These dynamic changes in axonal conduction may contribute to the physiology and pathophysiology of the brain. © 2014 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  7. Determination of Nerve Fiber Diameter Distribution From Compound Action Potential: A Continuous Approach.

    PubMed

    Un, M Kerem; Kaghazchi, Hamed

    2018-01-01

    When a signal is initiated in the nerve, it is transmitted along each nerve fiber via an action potential (called single fiber action potential (SFAP)) which travels with a velocity that is related with the diameter of the fiber. The additive superposition of SFAPs constitutes the compound action potential (CAP) of the nerve. The fiber diameter distribution (FDD) in the nerve can be computed from the CAP data by solving an inverse problem. This is usually achieved by dividing the fibers into a finite number of diameter groups and solve a corresponding linear system to optimize FDD. However, number of fibers in a nerve can be measured sometimes in thousands and it is possible to assume a continuous distribution for the fiber diameters which leads to a gradient optimization problem. In this paper, we have evaluated this continuous approach to the solution of the inverse problem. We have utilized an analytical function for SFAP and an assumed a polynomial form for FDD. The inverse problem involves the optimization of polynomial coefficients to obtain the best estimate for the FDD. We have observed that an eighth order polynomial for FDD can capture both unimodal and bimodal fiber distributions present in vivo, even in case of noisy CAP data. The assumed FDD distribution regularizes the ill-conditioned inverse problem and produces good results.

  8. Modeling specific action potentials in the human atria based on a minimal single-cell model.

    PubMed

    Richter, Yvonne; Lind, Pedro G; Maass, Philipp

    2018-01-01

    We present an effective method to model empirical action potentials of specific patients in the human atria based on the minimal model of Bueno-Orovio, Cherry and Fenton adapted to atrial electrophysiology. In this model, three ionic are currents introduced, where each of it is governed by a characteristic time scale. By applying a nonlinear optimization procedure, a best combination of the respective time scales is determined, which allows one to reproduce specific action potentials with a given amplitude, width and shape. Possible applications for supporting clinical diagnosis are pointed out.

  9. Evaluating the Potential of Commercial GIS for Accelerator Configuration Management

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    T.L. Larrieu; Y.R. Roblin; K. White

    2005-10-10

    The Geographic Information System (GIS) is a tool used by industries needing to track information about spatially distributed assets. A water utility, for example, must know not only the precise location of each pipe and pump, but also the respective pressure rating and flow rate of each. In many ways, an accelerator such as CEBAF (Continuous Electron Beam Accelerator Facility) can be viewed as an ''electron utility''. Whereas the water utility uses pipes and pumps, the ''electron utility'' uses magnets and RF cavities. At Jefferson lab we are exploring the possibility of implementing ESRI's ArcGIS as the framework for buildingmore » an all-encompassing accelerator configuration database that integrates location, configuration, maintenance, and connectivity details of all hardware and software. The possibilities of doing so are intriguing. From the GIS, software such as the model server could always extract the most-up-to-date layout information maintained by the Survey & Alignment for lattice modeling. The Mechanical Engineering department could use ArcGIS tools to generate CAD drawings of machine segments from the same database. Ultimately, the greatest benefit of the GIS implementation could be to liberate operators and engineers from the limitations of the current system-by-system view of machine configuration and allow a more integrated regional approach. The commercial GIS package provides a rich set of tools for database-connectivity, versioning, distributed editing, importing and exporting, and graphical analysis and querying, and therefore obviates the need for much custom development. However, formidable challenges to implementation exist and these challenges are not only technical and manpower issues, but also organizational ones. The GIS approach would crosscut organizational boundaries and require departments, which heretofore have had free reign to manage their own data, to cede some control and agree to a centralized framework.« less

  10. Onset dynamics of action potentials in rat neocortical neurons and identified snail neurons: quantification of the difference.

    PubMed

    Volgushev, Maxim; Malyshev, Aleksey; Balaban, Pavel; Chistiakova, Marina; Volgushev, Stanislav; Wolf, Fred

    2008-04-09

    The generation of action potentials (APs) is a key process in the operation of nerve cells and the communication between neurons. Action potentials in mammalian central neurons are characterized by an exceptionally fast onset dynamics, which differs from the typically slow and gradual onset dynamics seen in identified snail neurons. Here we describe a novel method of analysis which provides a quantitative measure of the onset dynamics of action potentials. This method captures the difference between the fast, step-like onset of APs in rat neocortical neurons and the gradual, exponential-like AP onset in identified snail neurons. The quantitative measure of the AP onset dynamics, provided by the method, allows us to perform quantitative analyses of factors influencing the dynamics.

  11. Onset Dynamics of Action Potentials in Rat Neocortical Neurons and Identified Snail Neurons: Quantification of the Difference

    PubMed Central

    Volgushev, Maxim; Malyshev, Aleksey; Balaban, Pavel; Chistiakova, Marina; Volgushev, Stanislav; Wolf, Fred

    2008-01-01

    The generation of action potentials (APs) is a key process in the operation of nerve cells and the communication between neurons. Action potentials in mammalian central neurons are characterized by an exceptionally fast onset dynamics, which differs from the typically slow and gradual onset dynamics seen in identified snail neurons. Here we describe a novel method of analysis which provides a quantitative measure of the onset dynamics of action potentials. This method captures the difference between the fast, step-like onset of APs in rat neocortical neurons and the gradual, exponential-like AP onset in identified snail neurons. The quantitative measure of the AP onset dynamics, provided by the method, allows us to perform quantitative analyses of factors influencing the dynamics. PMID:18398478

  12. Ranolazine inhibits shear sensitivity of endogenous Na+ current and spontaneous action potentials in HL-1 cells

    PubMed Central

    Strege, Peter; Beyder, Arthur; Bernard, Cheryl; Crespo-Diaz, Ruben; Behfar, Atta; Terzic, Andre; Ackerman, Michael; Farrugia, Gianrico

    2012-01-01

    NaV1.5 is a mechanosensitive voltage-gated Na+ channel encoded by the gene SCN5A, expressed in cardiac myocytes and required for phase 0 of the cardiac action potential (AP). In the cardiomyocyte, ranolazine inhibits depolarizing Na+ current and delayed rectifier (IKr) currents. Recently, ranolazine was also shown to be an inhibitor of NaV1.5 mechanosensitivity. Stretch also accelerates the firing frequency of the SA node, and fluid shear stress increases the beating rate of cultured cardiomyocytes in vitro. However, no cultured cell platform exists currently for examination of spontaneous electrical activity in response to mechanical stimulation. In the present study, flow of solution over atrial myocyte-derived HL-1 cultured cells was used to study shear stress mechanosensitivity of Na+ current and spontaneous, endogenous rhythmic action potentials. In voltage-clamped HL-1 cells, bath flow increased peak Na+ current by 14 ± 5%. In current-clamped cells, bath flow increased the frequency and decay rate of AP by 27 ± 12% and 18 ± 4%, respectively. Ranolazine blocked both responses to shear stress. This study suggests that cultured HL-1 cells are a viable in vitro model for detailed study of the effects of mechanical stimulation on spontaneous cardiac action potentials. Inhibition of the frequency and decay rate of action potentials in HL-1 cells are potential mechanisms behind the antiarrhythmic effect of ranolazine. PMID:23018927

  13. Initiation and blocking of the action potential in an axon in weak ultrasonic or microwave fields

    NASA Astrophysics Data System (ADS)

    Shneider, M. N.; Pekker, M.

    2014-05-01

    In this paper, we analyze the effect of the redistribution of the transmembrane ion channels in an axon caused by longitudinal acoustic vibrations of the membrane. These oscillations can be excited by an external source of ultrasound and weak microwave radiation interacting with the charges sitting on the surface of the lipid membrane. It is shown, using the Hodgkin-Huxley model of the axon, that the density redistribution of transmembrane sodium channels may reduce the threshold of the action potential, up to its spontaneous initiation. At the significant redistribution of sodium channels in the membrane, the rarefaction zones of the transmembrane channel density are formed, blocking the propagation of the action potential. Blocking the action potential propagation along the axon is shown to cause anesthesia in the example case of a squid axon. Various approaches to experimental observation of the effects considered in this paper are discussed.

  14. Data on the configuration design of internet-connected home cooling systems by engineering students.

    PubMed

    McComb, Christopher; Cagan, Jonathan; Kotovsky, Kenneth

    2017-10-01

    This experiment was carried out to record the step-by-step actions that humans take in solving a configuration design problem, either in small teams or individually. Specifically, study participants were tasked with configuring an internet-connected system of products to maintain temperature within a home, subject to cost constraints. Every participant was given access to a computer-based design interface that allowed them to construct and assess solutions. The interface was also used to record the data that is presented here. In total, data was collected for 68 participants, and each participant was allowed to perform 50 design actions in solving the configuration design problem. Major results based on the data presented here have been reported separately, including initial behavioral analysis (McComb et al.) [1], [2] and design pattern assessments via Markovian modeling (McComb et al., 2017; McComb et al., 2017) [3], [4].

  15. The afterhyperpolarizing potential following a train of action potentials is suppressed in an acute epilepsy model in the rat Cornu Ammonis 1 area.

    PubMed

    Kernig, K; Kirschstein, T; Würdemann, T; Rohde, M; Köhling, R

    2012-01-10

    In hippocampal Cornu Ammonis 1 (CA1) neurons, a prolonged depolarization evokes a train of action potentials followed by a prominent afterhyperpolarizing potential (AHP), which critically dampens neuronal excitability. Because it is not known whether epileptiform activity alters the AHP and whether any alteration of the AHP is independent of inhibition, we acutely induced epileptiform activity by bath application of the GABA(A) receptor blocker gabazine (5 μM) in the rat hippocampal slice preparation and studied its impact on the AHP using intracellular recordings. Following 10 min of gabazine wash-in, slices started to develop spontaneous epileptiform discharges. This disinhibition was accompanied by a significant shift of the resting membrane potential of CA1 neurons to more depolarized values. Prolonged depolarizations (600 ms) elicited a train of action potentials, the number of which was not different between baseline and gabazine treatment. However, the AHP following the train of action potentials was significantly reduced after 20 min of gabazine treatment. When the induction of epileptiform activity was prevented by co-application of 6-cyano-7-nitroquinoxaline-2,3-dione disodium (CNQX, 10 μM) and D-(-)-2-amino-5-phosphonopentanoic acid (D-AP5, 50 μM) to block α-amino-3-hydroxy-5-methylisoxazolepropionate (AMPA) and N-methyl-d-aspartate (NMDA) receptors, respectively, the AHP was preserved despite of GABA(A) receptor inhibition suggesting that the epileptiform activity was required to suppress the AHP. Moreover, the AHP was also preserved when the slices were treated with the protein kinase blockers H-9 (100 μM) and H-89 (1 μM). These results demonstrate that the AHP following a train of action potentials is rapidly suppressed by acutely induced epileptiform activity due to a phosphorylation process-presumably involving protein kinase A. Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.

  16. Outcome producing potential influences twelve-month-olds' interpretation of a novel action as goal-directed.

    PubMed

    Biro, Szilvia; Verschoor, Stephan; Coalter, Esther; Leslie, Alan M

    2014-11-01

    Learning about a novel, goal-directed action is a complex process. It requires identifying the outcome of the action and linking the action to its outcome for later use in new situations to predict the action or to anticipate its outcome. We investigated the hypothesis that linking a novel action to a salient change in the environment is critical for infants to assign a goal to the novel action. We report a study in which we show that 12-month-old infants, who were provided with prior experience with a novel action accompanied with a salient visible outcome in one context, can interpret the same action as goal-directed even in the absence of the outcome in another context. Our control condition shows that prior experience with the action, but without the salient effect, does not lead to goal-directed interpretation of the novel action. We also found that, for the case of 9-month-olds infants, prior experience with the outcome producing potential of the novel action does not facilitate a goal-directed interpretation of the action. However, this failure was possibly due to difficulties with generalizing the learnt association to another context rather than with linking the action to its outcome. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. Nanoelectronics-biology frontier: From nanoscopic probes for action potential recording in live cells to three-dimensional cyborg tissues.

    PubMed

    Duan, Xiaojie; Fu, Tian-Ming; Liu, Jia; Lieber, Charles M

    2013-08-01

    Semiconductor nanowires configured as the active channels of field-effect transistors (FETs) have been used as detectors for high-resolution electrical recording from single live cells, cell networks, tissues and organs. Extracellular measurements with substrate supported silicon nanowire (SiNW) FETs, which have projected active areas orders of magnitude smaller than conventional microfabricated multielectrode arrays (MEAs) and planar FETs, recorded action potential and field potential signals with high signal-to-noise ratio and temporal resolution from cultured neurons, cultured cardiomyocytes, acute brain slices and whole animal hearts. Measurements made with modulation-doped nanoscale active channel SiNW FETs demonstrate that signals recorded from cardiomyocytes are highly localized and have improved time resolution compared to larger planar detectors. In addition, several novel three-dimensional (3D) transistor probes, which were realized using advanced nanowire synthesis methods, have been implemented for intracellular recording. These novel probes include (i) flexible 3D kinked nanowire FETs, (ii) branched intracellular nanotube SiNW FETs, and (iii) active silicon nanotube FETs. Following phospholipid modification of the probes to mimic the cell membrane, the kinked nanowire, branched intracellular nanotube and active silicon nanotube FET probes recorded full-amplitude intracellular action potentials from spontaneously firing cardiomyocytes. Moreover, these probes demonstrated the capability of reversible, stable, and long-term intracellular recording, thus indicating the minimal invasiveness of the new nanoscale structures and suggesting biomimetic internalization via the phospholipid modification. Simultaneous, multi-site intracellular recording from both single cells and cell networks were also readily achieved by interfacing independently addressable nanoprobe devices with cells. Finally, electronic and biological systems have been seamlessly merged in 3D

  18. Nanoelectronics-biology frontier: From nanoscopic probes for action potential recording in live cells to three-dimensional cyborg tissues

    PubMed Central

    Duan, Xiaojie; Fu, Tian-Ming; Liu, Jia; Lieber, Charles M.

    2013-01-01

    Summary Semiconductor nanowires configured as the active channels of field-effect transistors (FETs) have been used as detectors for high-resolution electrical recording from single live cells, cell networks, tissues and organs. Extracellular measurements with substrate supported silicon nanowire (SiNW) FETs, which have projected active areas orders of magnitude smaller than conventional microfabricated multielectrode arrays (MEAs) and planar FETs, recorded action potential and field potential signals with high signal-to-noise ratio and temporal resolution from cultured neurons, cultured cardiomyocytes, acute brain slices and whole animal hearts. Measurements made with modulation-doped nanoscale active channel SiNW FETs demonstrate that signals recorded from cardiomyocytes are highly localized and have improved time resolution compared to larger planar detectors. In addition, several novel three-dimensional (3D) transistor probes, which were realized using advanced nanowire synthesis methods, have been implemented for intracellular recording. These novel probes include (i) flexible 3D kinked nanowire FETs, (ii) branched intracellular nanotube SiNW FETs, and (iii) active silicon nanotube FETs. Following phospholipid modification of the probes to mimic the cell membrane, the kinked nanowire, branched intracellular nanotube and active silicon nanotube FET probes recorded full-amplitude intracellular action potentials from spontaneously firing cardiomyocytes. Moreover, these probes demonstrated the capability of reversible, stable, and long-term intracellular recording, thus indicating the minimal invasiveness of the new nanoscale structures and suggesting biomimetic internalization via the phospholipid modification. Simultaneous, multi-site intracellular recording from both single cells and cell networks were also readily achieved by interfacing independently addressable nanoprobe devices with cells. Finally, electronic and biological systems have been seamlessly

  19. The face evoked steady-state visual potentials are sensitive to the orientation, viewpoint, expression and configuration of the stimuli.

    PubMed

    Vakli, Pál; Németh, Kornél; Zimmer, Márta; Kovács, Gyula

    2014-12-01

    Previous studies demonstrated that the steady-state visual-evoked potential (SSVEP) is reduced to the repetition of the same identity face when compared with the presentation of different identities, suggesting high-level neural adaptation to face identity. Here we investigated whether the SSVEP is sensitive to the orientation, viewpoint, expression and configuration of faces (Experiment 1), and whether adaptation to identity at the level of the SSVEP is robust enough to generalize across these properties (Experiment 2). In Experiment 1, repeating the same identity face with continuously changing orientation, viewpoint or expression evoked a larger SSVEP than the repetition of an unchanged face, presumably reflecting a release of adaptation. A less robust effect was observed in the case of changes affecting face configuration. In Experiment 2, we found a similar release of adaptation for faces with changing orientation, viewpoint and configuration, as there was no difference between the SSVEP for the same and different identity faces. However, we found an adaptation effect for faces with changing expressions, suggesting that face identity coding, as reflected in the SSVEP, is largely independent of the emotion displayed by faces. Taken together, these results imply that the SSVEP taps high-level face representations which abstract away from the changeable aspects of the face and likely incorporate information about face configuration, but which are specific to the orientation and viewpoint of the face. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. Modeling the attenuation and failure of action potentials in the dendrites of hippocampal neurons.

    PubMed Central

    Migliore, M

    1996-01-01

    We modeled two different mechanisms, a shunting conductance and a slow sodium inactivation, to test whether they could modulate the active propagation of a train of action potentials in a dendritic tree. Computer simulations, using a compartmental model of a pyramidal neuron, suggest that each of these two mechanisms could account for the activity-dependent attenuation and failure of the action potentials in the dendrites during the train. Each mechanism is shown to be in good qualitative agreement with experimental findings on somatic or dendritic stimulation and on the effects of hyperpolarization. The conditions under which branch point failures can be observed, and a few experimentally testable predictions, are presented and discussed. PMID:8913580

  1. Carbon monoxide effects on human ventricle action potential assessed by mathematical simulations

    PubMed Central

    Trenor, Beatriz; Cardona, Karen; Saiz, Javier; Rajamani, Sridharan; Belardinelli, Luiz; Giles, Wayne R.

    2013-01-01

    Carbon monoxide (CO) that is produced in a number of different mammalian tissues is now known to have significant effects on the cardiovascular system. These include: (i) vasodilation, (ii) changes in heart rate and strength of contractions, and (iii) modulation of autonomic nervous system input to both the primary pacemaker and the working myocardium. Excessive CO in the environment is toxic and can initiate or mediate life threatening cardiac rhythm disturbances. Recent reports link these ventricular arrhythmias to an increase in the slowly inactivating, or “late” component of the Na+ current in the mammalian heart. The main goal of this paper is to explore the basis of this pro-arrhythmic capability of CO by incorporating changes in CO-induced ion channel activity with intracellular signaling pathways in the mammalian heart. To do this, a quite well-documented mathematical model of the action potential and intracellular calcium transient in the human ventricular myocyte has been employed. In silico iterations based on this model provide a useful first step in illustrating the cellular electrophysiological consequences of CO that have been reported from mammalian heart experiments. Specifically, when the Grandi et al. model of the human ventricular action potential is utilized, and after the Na+ and Ca2+ currents in a single myocyte are modified based on the experimental literature, early after-depolarization (EAD) rhythm disturbances appear, and important elements of the underlying causes of these EADs are revealed/illustrated. Our modified mathematical model of the human ventricular action potential also provides a convenient digital platform for designing future experimental work and relating these changes in cellular cardiac electrophysiology to emerging clinical and epidemiological data on CO toxicity. PMID:24146650

  2. Action potential propagation recorded from single axonal arbors using multi-electrode arrays.

    PubMed

    Tovar, Kenneth R; Bridges, Daniel C; Wu, Bian; Randall, Connor; Audouard, Morgane; Jang, Jiwon; Hansma, Paul K; Kosik, Kenneth S

    2018-04-11

    We report the presence of co-occurring extracellular action potentials (eAPs) from cultured mouse hippocampal neurons among groups of planar electrodes on multi-electrode arrays (MEAs). The invariant sequences of eAPs among co-active electrode groups, repeated co-occurrences and short inter-electrode latencies are consistent with action potential propagation in unmyelinated axons. Repeated eAP co-detection by multiple electrodes was widespread in all our data records. Co-detection of eAPs confirms they result from the same neuron and allows these eAPs to be isolated from all other spikes independently of spike sorting algorithms. We averaged co-occurring events and revealed additional electrodes with eAPs that would otherwise be below detection threshold. We used these eAP cohorts to explore the temperature sensitivity of action potential propagation and the relationship between voltage-gated sodium channel density and propagation velocity. The sequence of eAPs among co-active electrodes 'fingerprints' neurons giving rise to these events and identifies them within neuronal ensembles. We used this property and the non-invasive nature of extracellular recording to monitor changes in excitability at multiple points in single axonal arbors simultaneously over several hours, demonstrating independence of axonal segments. Over several weeks, we recorded changes in inter-electrode propagation latencies and ongoing changes in excitability in different regions of single axonal arbors. Our work illustrates how repeated eAP co-occurrences can be used to extract physiological data from single axons with low electrode density MEAs. However, repeated eAP co-occurrences leads to over-sampling spikes from single neurons and thus can confound traditional spike-train analysis.

  3. [Conversion of sound into auditory nerve action potentials].

    PubMed

    Encke, J; Kreh, J; Völk, F; Hemmert, W

    2016-11-01

    Outer hair cells play a major role in the hearing process: they amplify the motion of the basilar membrane up to a 1000-fold and at the same time sharpen the excitation patterns. These patterns are converted by inner hair cells into action potentials of the auditory nerve. Outer hair cells are delicate structures and easily damaged, e. g., by overexposure to noise. Hearing aids can amplify the amplitude of the excitation patterns, but they cannot restore their degraded frequency selectivity. Noise overexposure also leads to delayed degeneration of auditory nerve fibers, particularly those with low a spontaneous rate, which are important for the coding of sound in noise. However, this loss cannot be diagnosed by pure-tone audiometry.

  4. The human ether-a-go-go-related gene (hERG) current inhibition selectively prolongs action potential of midmyocardial cells to augment transmural dispersion.

    PubMed

    Yasuda, C; Yasuda, S; Yamashita, H; Okada, J; Hisada, T; Sugiura, S

    2015-08-01

    The majority of drug induced arrhythmias are related to the prolongation of action potential duration following inhibition of rapidly activating delayed rectifier potassium current (I(Kr)) mediated by the hERG channel. However, for arrhythmias to develop and be sustained, not only the prolongation of action potential duration but also its transmural dispersion are required. Herein, we evaluated the effect of hERG inhibition on transmural dispersion of action potential duration using the action potential clamp technique that combined an in silico myocyte model with the actual I(Kr) measurement. Whole cell I(Kr) current was measured in Chinese hamster ovary cells stably expressing the hERG channel. The measured current was coupled with models of ventricular endocardial, M-, and epicardial cells to calculate the action potentials. Action potentials were evaluated under control condition and in the presence of 1, 10, or 100 μM disopyramide, an hERG inhibitor. Disopyramide dose-dependently increased the action potential durations of the three cell types. However, action potential duration of M-cells increased disproportionately at higher doses, and was significantly different from that of epicardial and endocardial cells (dispersion of repolarization). By contrast, the effects of disopyramide on peak I(Kr) and instantaneous current-voltage relation were similar in all cell types. Simulation study suggested that the reduced repolarization reserve of M-cell with smaller amount of slowly activating delayed rectifier potassium current levels off at longer action potential duration to make such differences. The action potential clamp technique is useful for studying the mechanism of arrhythmogenesis by hERG inhibition through the transmural dispersion of repolarization.

  5. Elastic resistance change and action potential generation of non-faradaic Pt/TiO2/Pt capacitors.

    PubMed

    Lim, Hyungkwang; Jang, Ho Won; Lee, Doh-Kwon; Kim, Inho; Hwang, Cheol Seong; Jeong, Doo Seok

    2013-07-21

    Electric current in the mixed ionic-electronic conductor TiO2 is hysteretic, i.e. history-dependent, and its use is versatile in electronic devices. Nowadays, biologically inspired, analogue-type computing systems, known as neuromorphic systems, are being actively investigated owing to their new and intriguing physical concepts. The realization of artificial synapses is important for constructing neuromorphic systems. In mammalians' brains, the plasticity of synapses between neighbouring nerve cells arises from action potential firing. Emulating action potential firing via inorganic systems has therefore become important in neuromorphic engineering. In this work, the current-voltage hysteresis of TiO2-based non-faradaic capacitors is investigated to primarily focus on the correlation between the blocking contact and the elasticity, i.e. non-plasticity, of the capacitors' resistance change, in experimental and theoretical methods. The similarity between the action potential firing behaviour in nerve cells and the elasticity of the non-faradaic capacitors is addressed.

  6. Effects of boundaries and geometry on the spatial distribution of action potential duration in cardiac tissue

    PubMed Central

    Cherry, Elizabeth M.; Fenton, Flavio H.

    2011-01-01

    Increased dispersion of action potential duration across cardiac tissue has long been considered an important substrate for the development of most electrical arrhythmias. Although this dispersion has been studied previously by characterizing the static intrinsic gradients in cellular electrophysiology and dynamical gradients generated by fast pacing, few studies have concentrated on dispersions generated solely by structural effects. Here we show how boundaries and geometry can produce spatially dependent changes in action potential duration (APD) in homogeneous and isotropic tissue, where all the cells have the same APD in the absence of diffusion. Electrotonic currents due to coupling within the tissue and at the tissue boundaries can generate dispersion, and the profile of this dispersion can change dramatically depending on tissue size and shape, action potential morphology, tissue dimensionality, and stimulus frequency and location. The dispersion generated by pure geometrical effects can be on the order of tens of milliseconds, enough under certain conditions to produce conduction blocks and initiate reentrant waves. PMID:21762703

  7. Anti-addiction Drug Ibogaine Prolongs the Action Potential in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes.

    PubMed

    Rubi, Lena; Eckert, Daniel; Boehm, Stefan; Hilber, Karlheinz; Koenig, Xaver

    2017-04-01

    Ibogaine is a plant alkaloid used as anti-addiction drug in dozens of alternative medicine clinics worldwide. Recently, alarming reports of life-threatening cardiac arrhythmias and cases of sudden death associated with the ingestion of ibogaine have accumulated. Using whole-cell patch clamp recordings, we assessed the effects of ibogaine and its main metabolite noribogaine on action potentials in human ventricular-like cardiomyocytes derived from induced pluripotent stem cells. Therapeutic concentrations of ibogaine and its long-lived active metabolite noribogaine significantly retarded action potential repolarization in human cardiomyocytes. These findings represent the first experimental proof that ibogaine application entails a cardiac arrhythmia risk for humans. In addition, they explain the clinically observed delayed incidence of cardiac adverse events several days after ibogaine intake. We conclude that therapeutic concentrations of ibogaine retard action potential repolarization in the human heart. This may give rise to a prolongation of the QT interval in the electrocardiogram and cardiac arrhythmias.

  8. Event-related potential effects of superior action anticipation in professional badminton players.

    PubMed

    Jin, Hua; Xu, Guiping; Zhang, John X; Gao, Hongwei; Ye, Zuoer; Wang, Pin; Lin, Huiyan; Mo, Lei; Lin, Chong-De

    2011-04-04

    The ability to predict the trajectory of a ball based on the opponent's body kinematics has been shown to be critical to high-performing athletes in many sports. However, little is known about the neural correlates underlying such superior ability in action anticipation. The present event-related potential study compared brain responses from professional badminton players and non-player controls when they watched video clips of badminton games and predicted a ball's landing position. Replicating literature findings, the players made significantly more accurate judgments than the controls and showed better action anticipation. Correspondingly, they showed enlarged amplitudes of two ERP components, a P300 peaking around 350ms post-stimulus with a parietal scalp distribution and a P2 peaking around 250ms with a posterior-occipital distribution. The P300 effect was interpreted to reflect primed access and/or directing of attention to game-related memory representations in the players facilitating their online judgment of related actions. The P2 effect was suggested to reflect some generic learning effects. The results identify clear neural responses that differentiate between different levels of action anticipation associated with sports expertise. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  9. Modeling the action-potential-sensitive nonlinear-optical response of myelinated nerve fibers and short-term memory

    NASA Astrophysics Data System (ADS)

    Shneider, M. N.; Voronin, A. A.; Zheltikov, A. M.

    2011-11-01

    The Goldman-Albus treatment of the action-potential dynamics is combined with a phenomenological description of molecular hyperpolarizabilities into a closed-form model of the action-potential-sensitive second-harmonic response of myelinated nerve fibers with nodes of Ranvier. This response is shown to be sensitive to nerve demyelination, thus enabling an optical diagnosis of various demyelinating diseases, including multiple sclerosis. The model is applied to examine the nonlinear-optical response of a three-neuron reverberating circuit—the basic element of short-term memory.

  10. Analysis of electrically evoked compound action potential of the auditory nerve in children with bilateral cochlear implants.

    PubMed

    Caldas, Fernanda Ferreira; Cardoso, Carolina Costa; Barreto, Monique Antunes de Souza Chelminski; Teixeira, Marina Santos; Hilgenberg, Anacléia Melo da Silva; Serra, Lucieny Silva Martins; Bahmad Junior, Fayez

    2016-01-01

    The cochlear implant device has the capacity to measure the electrically evoked compound action potential of the auditory nerve. The neural response telemetry is used in order to measure the electrically evoked compound action potential of the auditory nerve. To analyze the electrically evoked compound action potential, through the neural response telemetry, in children with bilateral cochlear implants. This is an analytical, prospective, longitudinal, historical cohort study. Six children, aged 1-4 years, with bilateral cochlear implant were assessed at five different intervals during their first year of cochlear implant use. There were significant differences in follow-up time (p=0.0082) and electrode position (p=0.0019) in the T-NRT measure. There was a significant difference in the interaction between time of follow-up and electrode position (p=0.0143) when measuring the N1-P1 wave amplitude between the three electrodes at each time of follow-up. The electrically evoked compound action potential measurement using neural response telemetry in children with bilateral cochlear implants during the first year of follow-up was effective in demonstrating the synchronized bilateral development of the peripheral auditory pathways in the studied population. Copyright © 2015 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

  11. Action potential broadening in a presynaptic channelopathy

    NASA Astrophysics Data System (ADS)

    Begum, Rahima; Bakiri, Yamina; Volynski, Kirill E.; Kullmann, Dimitri M.

    2016-07-01

    Brain development and interictal function are unaffected in many paroxysmal neurological channelopathies, possibly explained by homoeostatic plasticity of synaptic transmission. Episodic ataxia type 1 is caused by missense mutations of the potassium channel Kv1.1, which is abundantly expressed in the terminals of cerebellar basket cells. Presynaptic action potentials of small inhibitory terminals have not been characterized, and it is not known whether developmental plasticity compensates for the effects of Kv1.1 dysfunction. Here we use visually targeted patch-clamp recordings from basket cell terminals of mice harbouring an ataxia-associated mutation and their wild-type littermates. Presynaptic spikes are followed by a pronounced afterdepolarization, and are broadened by pharmacological blockade of Kv1.1 or by a dominant ataxia-associated mutation. Somatic recordings fail to detect such changes. Spike broadening leads to increased Ca2+ influx and GABA release, and decreased spontaneous Purkinje cell firing. We find no evidence for developmental compensation for inherited Kv1.1 dysfunction.

  12. Potential description of the charmonium from lattice QCD

    NASA Astrophysics Data System (ADS)

    Kawanai, Taichi; Sasaki, Shoichi

    2016-01-01

    We present spin-independent and spin-spin interquark potentials for charmonium states, that are calculated using a relativistic heavy quark action for charm quarks on the PACS-CS gauge configurations generated with the Iwasaki gauge action and 2+1 flavors of Wilson clover quark. The interquark potential with finite quark masses is defined through the equal-time Bethe-Salpeter amplitude. The light and strange quark masses are close to the physical point where the pion mass corresponds to Mπ ≈ 156(7) MeV, and charm quark mass is tuned to reproduce the experimental values of ηc and J/ψ states. Our simulations are performed with a lattice cutoff of a-1 ≈ 2.2 GeV and a spatial volume of (3 fm)3. We solve the nonrelativistic Schrödinger equation with resulting charmonium potentials as theoretical inputs. The resultant charmonium spectrum below the open charm threshold shows a fairly good agreement with experimental data of well-established charmonium states.

  13. Action Learning: Avoiding Conflict or Enabling Action

    ERIC Educational Resources Information Center

    Corley, Aileen; Thorne, Ann

    2006-01-01

    Action learning is based on the premise that action and learning are inextricably entwined and it is this potential, to enable action, which has contributed to the growth of action learning within education and management development programmes. However has this growth in action learning lead to an evolution or a dilution of Revan's classical…

  14. Beat-to-beat variability of cardiac action potential duration: underlying mechanism and clinical implications.

    PubMed

    Nánási, Péter P; Magyar, János; Varró, András; Ördög, Balázs

    2017-10-01

    Beat-to-beat variability of cardiac action potential duration (short-term variability, SV) is a common feature of various cardiac preparations, including the human heart. Although it is believed to be one of the best arrhythmia predictors, the underlying mechanisms are not fully understood at present. The magnitude of SV is basically determined by the intensity of cell-to-cell coupling in multicellular preparations and by the duration of the action potential (APD). To compensate for the APD-dependent nature of SV, the concept of relative SV (RSV) has been introduced by normalizing the changes of SV to the concomitant changes in APD. RSV is reduced by I Ca , I Kr , and I Ks while increased by I Na , suggesting that ion currents involved in the negative feedback regulation of APD tend to keep RSV at a low level. RSV is also influenced by intracellular calcium concentration and tissue redox potential. The clinical implications of APD variability is discussed in detail.

  15. Generalized alternating stimulation: a novel method to reduce stimulus artifact in electrically evoked compound action potentials.

    PubMed

    Alvarez, Isaac; de la Torre, Angel; Sainz, Manuel; Roldan, Cristina; Schoesser, Hansjoerg; Spitzer, Philipp

    2007-09-15

    Stimulus artifact is one of the main limitations when considering electrically evoked compound action potential for clinical applications. Alternating stimulation (average of recordings obtained with anodic-cathodic and cathodic-anodic bipolar stimulation pulses) is an effective method to reduce stimulus artifact when evoked potentials are recorded. In this paper we extend the concept of alternating stimulation by combining anodic-cathodic and cathodic-anodic recordings with a weight in general different to 0.5. We also provide an automatic method to obtain an estimation of the optimal weights. Comparison with conventional alternating, triphasic stimulation and masker-probe paradigm shows that the generalized alternating method improves the quality of electrically evoked compound action potential responses.

  16. Head-on collision of multistate ultralight BEC dark matter configurations

    NASA Astrophysics Data System (ADS)

    Guzmán, F. S.; Avilez, Ana A.

    2018-06-01

    Density profiles of ultralight Bose-condensate dark matter inferred from numerical simulations of structure formation, ruled by the Gross-Pitaevskii-Poisson (GPP) system of equations, have a core-tail structure. Multistate equilibrium configurations of the GPP system, on the other hand, have a similar core-tail density profile. We now submit these multistate configurations to highly dynamical scenarios and show their potential as providers of appropriate density profiles of structures. We present the simulation of head-on collisions between two equilibrium configurations of the GPP system of equations, including the collision of ground state with multistate configurations. We study the regimes of solitonic and merger behavior and show generic properties of the dynamics of the system, including the relaxation process and attractor density profiles. We show that the merger of multistate configurations has the potential to produce core-tail density profiles, with the core dominated by the ground state and the halo dominated by an additional state.

  17. On the Power Spectrum of Motor Unit Action Potential Trains Synchronized With Mechanical Vibration.

    PubMed

    Romano, Maria; Fratini, Antonio; Gargiulo, Gaetano D; Cesarelli, Mario; Iuppariello, Luigi; Bifulco, Paolo

    2018-03-01

    This study provides a definitive analysis of the spectrum of a motor unit action potential train (MUAPT) elicited by mechanical vibratory stimulation via a detailed and concise mathematical formulation. Experimental studies demonstrated that MUAPs are not exactly synchronized with the vibratory stimulus but show a variable latency jitter, whose effects have not been investigated yet. Synchronized action potential train was represented as a quasi-periodic sequence of a given MU waveform. The latency jitter of action potentials was modeled as a Gaussian stochastic process, in accordance to the previous experimental studies. A mathematical expression for power spectrum of a synchronized MUAPT has been derived. The spectrum comprises a significant continuous component and discrete components at the vibratory frequency and its harmonics. Their relevance is correlated to the level of synchronization: the weaker the synchronization the more relevant is the continuous spectrum. Electromyography (EMG) rectification enhances the discrete components. The derived equations have general validity and well describe the power spectrum of actual EMG recordings during vibratory stimulation. Results are obtained by appropriately setting the level of synchronization and vibration frequency. This paper definitively clarifies the nature of changes in spectrum of raw EMG recordings from muscles undergoing vibratory stimulation. Results confirm the need of motion artifact filtering for raw EMG recordings during stimulation and strongly suggest to avoid EMG rectification that significantly alters the spectrum characteristics.

  18. Hybrid Wing Body Configuration Scaling Study

    NASA Technical Reports Server (NTRS)

    Nickol, Craig L.

    2012-01-01

    The Hybrid Wing Body (HWB) configuration is a subsonic transport aircraft concept with the potential to simultaneously reduce fuel burn, noise and emissions compared to conventional concepts. Initial studies focused on very large applications with capacities for up to 800 passengers. More recent studies have focused on the large, twin-aisle class with passenger capacities in the 300-450 range. Efficiently scaling this concept down to the single aisle or smaller size is challenging due to geometric constraints, potentially reducing the desirability of this concept for applications in the 100-200 passenger capacity range or less. In order to quantify this scaling challenge, five advanced conventional (tube-and-wing layout) concepts were developed, along with equivalent (payload/range/technology) HWB concepts, and their fuel burn performance compared. The comparison showed that the HWB concepts have fuel burn advantages over advanced tube-and-wing concepts in the larger payload/range classes (roughly 767-sized and larger). Although noise performance was not quantified in this study, the HWB concept has distinct noise advantages over the conventional tube-and-wing configuration due to the inherent noise shielding features of the HWB. NASA s Environmentally Responsible Aviation (ERA) project will continue to investigate advanced configurations, such as the HWB, due to their potential to simultaneously reduce fuel burn, noise and emissions.

  19. Vitamin K modulates cardiac action potential by blocking sodium and potassium ion channels.

    PubMed

    Drolet, B; Emond, A; Fortin, V; Daleau, P; Rousseau, G; Cardinal, R; Turgeon, J

    2000-10-01

    Cardiovascular collapses, syncopes, and sudden deaths have been observed following the rapid administration of intravenous vitamin K. Our objectives were to characterize the effects of vitamin K on cardiac action potentials and to evaluate effects of vitamin K on sodium and potassium currents, namely I(Na), I(Kr), and I(Ks). Guinea pig hearts (n = 21) were paced at a cycle length of 250 msec and exposed to vitamin K at 1.15-4.6 micromol/L (2.5-10 mg/L). Monophasic action potential duration measured at 90% repolarization (MAPD(90)) was not significantly reduced (-1.6 +/- 0.3 msec; P >.05; N.S.) at 1.15 micromol/L, but increased by 6.5 +/- 0.4 msec (P <.05) at 2.3 micromol/L. MAPD(90) was not measurable at 4.6 micromol/L, as a result of inexcitability. Patch-clamp experiments in ventricular myocytes demonstrated a approximately 50% reduction in I(Na) by 10 micromol/L vitamin K and a concentration-dependent reduction of the K(+) current elicited by short depolarizations (250 msec; I(K250)). Estimated IC(50) for I(K250), mostly representing I(Kr), was 2.3 micromol/L. Vitamin K was less potent to block the K(+) current elicited by long depolarizations (5,000 msec; I(K5000)), mostly representing I(Ks), with an estimated IC(50) over 100 micromol/L. Therapeutic concentrations ( approximately 1.5 micromol/L) of intravenous vitamin K modulate cardiac action potential by blocking ionic currents involved in cardiac depolarization and repolarization.

  20. The Mechanism of Action of Zingerone in the Pacemaker Potentials of Interstitial Cells of Cajal Isolated from Murine Small Intestine.

    PubMed

    Kim, Jung Nam; Kim, Hyun Jung; Kim, Iksung; Kim, Yun Tai; Kim, Byung Joo

    2018-01-01

    Zingerone, a major component found in ginger root, is clinically effective for the treatment of various diseases. Interstitial cells of Cajal (ICCs) are the pacemaker cells responsible for slow waves in the gastrointestinal (GI) tract. We investigated the effects of zingerone on the pacemaker potentials of ICCs to assess its mechanisms of action and its potential as a treatment for GI tract motility disorder. We isolated ICCs from small intestines, and the whole-cell patch-clamp configuration was used to record the pacemaker potentials in cultured ICCs. Under the current clamping mode, zingerone inhibited pacemaker potentials of ICCs concentration-dependently. These effects were blocked not by capsazepine, a transient receptor potential vanilloid 1 (TRPV1) channel blocker, but by glibenclamide, a specific ATP-sensitive K+ channel blocker. Pretreatment with SQ-22536 (an adenylate cyclase inhibitor), LY294002 (a phosphoinositide 3-kinase inhibitor), and calphostin C (a protein kinase C (PKC) inhibitor) did not block the effects of zingerone on the pacemaker potentials relative to treatment with zingerone alone. However, zingerone-induced pacemaker potential inhibition was blocked by 1H-[1,2,4] oxadiazolo [4,3-a] quinoxalin-1-one (ODQ; a guanylate cyclase inhibitor), KT5823 (a protein kinase G (PKG) inhibitor), and L-NAME (a non-selective nitric oxide synthase (NOS) inhibitor). In addition, zingerone stimulated cyclic guanosine monophosphate (cGMP) production in ICCs. Finally, pretreatment with PD98059 (a p42/44 mitogen-activated protein kinase (MAPK) inhibitor), SB203580 (a p38 MAPK inhibitor), and SP600125 (c-Jun N-terminal kinases (JNK)-specific inhibitor) blocked the zingerone-induced pacemaker potential inhibition. These results suggest that zingerone concentration-dependently inhibits pacemaker potentials of ICCs via NO/cGMP-dependent ATP-sensitive K+ channels through MAPK-dependent pathways. Taken together, this study shows that zingerone may have the potential

  1. Effect of an Educational Game on University Students' Learning about Action Potentials

    ERIC Educational Resources Information Center

    Luchi, Kelly Cristina Gaviao; Montrezor, Luís Henrique; Marcondes, Fernanda K.

    2017-01-01

    The aim of this study was to evaluate the effect of an educational game that is used for teaching the mechanisms of the action potentials in cell membranes. The game was composed of pieces representing the intracellular and extracellular environments, ions, ion channels, and the Na+-K+-ATPase pump. During the game activity, the students arranged…

  2. Pathological prolongation of action potential duration as a cause of the reduced alpha-adrenoceptor-mediated negative inotropy in streptozotocin-induced diabetic mice myocardium.

    PubMed

    Kanae, Haruna; Hamaguchi, Shogo; Wakasugi, Yumi; Kusakabe, Taichi; Kato, Keisuke; Namekata, Iyuki; Tanaka, Hikaru

    2017-11-01

    Effect of pathological prolongation of action potential duration on the α-adrenoceptor-mediated negative inotropy was studied in streptozotocin-induced diabetic mice myocardium. In streptozotocin-treated mouse ventricular myocardium, which had longer duration of action potential than that in control mice, the negative inotropic response induced by phenylephrine was smaller than that in control mice. 4-Aminopyridine prolonged the action potential duration and decreased the negative inotropy in control mice. Cromakalim shortened the action potential duration and increased the negative inotropy in streptozotocin-treated mice. These results suggest that the reduced α-adrenoceptor-mediated inotropy in the diabetic mouse myocardium is partly due to its prolonged action potential. Copyright © 2017 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

  3. Teachers in Action Research: Assumptions and Potentials

    ERIC Educational Resources Information Center

    Li, Yuen-Ling

    2008-01-01

    Research literature has long indicated that action research may stimulate practitioners themselves to actively evaluate the quality of their practice. This study is designed to report the use of action research for the development of early years professional practice by analyzing the pre-project and the post-project video-filmed teaching events.…

  4. Convex central configurations for the n-body problem

    NASA Astrophysics Data System (ADS)

    Xia, Zhihong

    We give a simple proof of a classical result of MacMillan and Bartky (Trans. Amer. Math. Soc. 34 (1932) 838) which states that, for any four positive masses and any assigned order, there is a convex planar central configuration. Moreover, we show that the central configurations we find correspond to local minima of the potential function with fixed moment of inertia. This allows us to show that there are at least six local minimum central configurations for the planar four-body problem. We also show that for any assigned order of five masses, there is at least one convex spatial central configuration of local minimum type. Our method also applies to some other cases.

  5. NASA/HAA Advanced Rotorcraft Technology and Tilt Rotor Workshop. Volume 6: Vehicle Configuration Session

    NASA Technical Reports Server (NTRS)

    1980-01-01

    Five high speed rotorcraft configurations are considered: the high speed helicopter, compound helicopter, ABC, tilt rotor and the X wing. The technology requirements and the recommended actions are discussed.

  6. An Excel‐based implementation of the spectral method of action potential alternans analysis

    PubMed Central

    Pearman, Charles M.

    2014-01-01

    Abstract Action potential (AP) alternans has been well established as a mechanism of arrhythmogenesis and sudden cardiac death. Proper interpretation of AP alternans requires a robust method of alternans quantification. Traditional methods of alternans analysis neglect higher order periodicities that may have greater pro‐arrhythmic potential than classical 2:1 alternans. The spectral method of alternans analysis, already widely used in the related study of microvolt T‐wave alternans, has also been used to study AP alternans. Software to meet the specific needs of AP alternans analysis is not currently available in the public domain. An AP analysis tool is implemented here, written in Visual Basic for Applications and using Microsoft Excel as a shell. This performs a sophisticated analysis of alternans behavior allowing reliable distinction of alternans from random fluctuations, quantification of alternans magnitude, and identification of which phases of the AP are most affected. In addition, the spectral method has been adapted to allow detection and quantification of higher order regular oscillations. Analysis of action potential morphology is also performed. A simple user interface enables easy import, analysis, and export of collated results. PMID:25501439

  7. An oscilloscope spot intensifier, to improve photographic recordings of action potentials.

    PubMed

    Evans, M H

    1985-06-01

    A circuit diagram is shown for a semiconductor device to intensify the brightness of an oscilloscope during the rapidly rising and falling phases of signals such as action potentials. Brightening pulses proportional in amplitude to the rate of change in the Y-axis are available for connection to an oscilloscope with an external intensity ('Z') modulation input. The circuit requires one transistor, one dual operational amplifier and two single fast operational amplifiers.

  8. CMS Configuration Editor: GUI based application for user analysis job

    NASA Astrophysics Data System (ADS)

    de Cosa, A.

    2011-12-01

    We present the user interface and the software architecture of the Configuration Editor for the CMS experiment. The analysis workflow is organized in a modular way integrated within the CMS framework that organizes in a flexible way user analysis code. The Python scripting language is adopted to define the job configuration that drives the analysis workflow. It could be a challenging task for users, especially for newcomers, to develop analysis jobs managing the configuration of many required modules. For this reason a graphical tool has been conceived in order to edit and inspect configuration files. A set of common analysis tools defined in the CMS Physics Analysis Toolkit (PAT) can be steered and configured using the Config Editor. A user-defined analysis workflow can be produced starting from a standard configuration file, applying and configuring PAT tools according to the specific user requirements. CMS users can adopt this tool, the Config Editor, to create their analysis visualizing in real time which are the effects of their actions. They can visualize the structure of their configuration, look at the modules included in the workflow, inspect the dependences existing among the modules and check the data flow. They can visualize at which values parameters are set and change them according to what is required by their analysis task. The integration of common tools in the GUI needed to adopt an object-oriented structure in the Python definition of the PAT tools and the definition of a layer of abstraction from which all PAT tools inherit.

  9. Spatiotemporal Phase Synchronization in Adaptive Reconfiguration from Action Observation Network to Mentalizing Network for Understanding Other's Action Intention.

    PubMed

    Zhang, Li; Gan, John Q; Zheng, Wenming; Wang, Haixian

    2018-05-01

    In action intention understanding, the mirror system is involved in perception-action matching process and the mentalizing system underlies higher-level intention inference. By analyzing the dynamic functional connectivity in α (8-12 Hz) and β (12-30 Hz) frequency bands over a "hand-cup interaction" observation task, this study investigates the topological transition from the action observation network (AON) to the mentalizing network (MZN), and estimates their functional relevance for intention identification from other's different action kinematics. Sequential brain microstates were extracted based on event-related potentials (ERPs), in which significantly differing neuronal responses were found in N170-P200 related to perceptually matching kinematic profiles and P400-700 involved in goal inference. Inter-electrode weighted phase lag index analysis on the ERP microstates revealed a shift of hub centrality salient in α frequency band, from the AON dominated by left-lateral frontal-premotor-temporal and temporal-parietooccipital synchronizations to the MZN consisting of more bilateral frontal-parietal and temporal-parietal synchronizations. As compared with usual actions, intention identification of unintelligible actions induces weaker synchronizations in the AON but dramatically increased connectivity in right frontal-temporal-parietal regions of the MZN, indicating a spatiotemporally complementary effect between the functional network configurations involved in mirror and mentalizing processes. Perceptual processing in observing usual/unintelligible actions decreases/increases requirements for intention inference, which would induce less/greater functional network reorganization on the way to mentalization. From the comparison, our study suggests that the adaptive topological changes from the AON to the MZN indicate implicit causal association between the mirror and mentalizing systems for decoding others' intentionality.

  10. The activity of spontaneous action potentials in developing hair cells is regulated by Ca(2+)-dependence of a transient K+ current.

    PubMed

    Levic, Snezana; Lv, Ping; Yamoah, Ebenezer N

    2011-01-01

    Spontaneous action potentials have been described in developing sensory systems. These rhythmic activities may have instructional roles for the functional development of synaptic connections. The importance of spontaneous action potentials in the developing auditory system is underpinned by the stark correlation between the time of auditory system functional maturity, and the cessation of spontaneous action potentials. A prominent K(+) current that regulates patterning of action potentials is I(A). This current undergoes marked changes in expression during chicken hair cell development. Although the properties of I(A) are not normally classified as Ca(2+)-dependent, we demonstrate that throughout the development of chicken hair cells, I(A) is greatly reduced by acute alterations of intracellular Ca(2+). As determinants of spike timing and firing frequency, intracellular Ca(2+) buffers shift the activation and inactivation properties of the current to more positive potentials. Our findings provide evidence to demonstrate that the kinetics and functional expression of I(A) are tightly regulated by intracellular Ca(2+). Such feedback mechanism between the functional expression of I(A) and intracellular Ca(2+) may shape the activity of spontaneous action potentials, thus potentially sculpting synaptic connections in an activity-dependent manner in the developing cochlea. © 2011 Levic et al.

  11. Voltage Gated Calcium Channel Activation by Backpropagating Action Potentials Downregulates NMDAR Function.

    PubMed

    Theis, Anne-Kathrin; Rózsa, Balázs; Katona, Gergely; Schmitz, Dietmar; Johenning, Friedrich W

    2018-01-01

    The majority of excitatory synapses are located on dendritic spines of cortical glutamatergic neurons. In spines, compartmentalized Ca 2+ signals transduce electrical activity into specific long-term biochemical and structural changes. Action potentials (APs) propagate back into the dendritic tree and activate voltage gated Ca 2+ channels (VGCCs). For spines, this global mode of spine Ca 2+ signaling is a direct biochemical feedback of suprathreshold neuronal activity. We previously demonstrated that backpropagating action potentials (bAPs) result in long-term enhancement of spine VGCCs. This activity-dependent VGCC plasticity results in a large interspine variability of VGCC Ca 2+ influx. Here, we investigate how spine VGCCs affect glutamatergic synaptic transmission. We combined electrophysiology, two-photon Ca 2+ imaging and two-photon glutamate uncaging in acute brain slices from rats. T- and R-type VGCCs were the dominant depolarization-associated Ca 2+ conductances in dendritic spines of excitatory layer 2 neurons and do not affect synaptic excitatory postsynaptic potentials (EPSPs) measured at the soma. Using two-photon glutamate uncaging, we compared the properties of glutamatergic synapses of single spines that express different levels of VGCCs. While VGCCs contributed to EPSP mediated Ca 2+ influx, the amount of EPSP mediated Ca 2+ influx is not determined by spine VGCC expression. On a longer timescale, the activation of VGCCs by bAP bursts results in downregulation of spine NMDAR function.

  12. Optical recording of action potentials and other discrete physiological events: a perspective from signal detection theory.

    PubMed

    Sjulson, Lucas; Miesenböck, Gero

    2007-02-01

    Optical imaging of physiological events in real time can yield insights into biological function that would be difficult to obtain by other experimental means. However, the detection of all-or-none events, such as action potentials or vesicle fusion events, in noisy single-trial data often requires a careful balance of tradeoffs. The analysis of such experiments, as well as the design of optical reporters and instrumentation for them, is aided by an understanding of the principles of signal detection. This review illustrates these principles, using as an example action potential recording with optical voltage reporters.

  13. Vorticity vector-potential method based on time-dependent curvilinear coordinates for two-dimensional rotating flows in closed configurations

    NASA Astrophysics Data System (ADS)

    Fu, Yuan; Zhang, Da-peng; Xie, Xi-lin

    2018-04-01

    In this study, a vorticity vector-potential method for two-dimensional viscous incompressible rotating driven flows is developed in the time-dependent curvilinear coordinates. The method is applicable in both inertial and non-inertial frames of reference with the advantage of a fixed and regular calculation domain. The numerical method is applied to triangle and curved triangle configurations in constant and varying rotational angular velocity cases respectively. The evolutions of flow field are studied. The geostrophic effect, unsteady effect and curvature effect on the evolutions are discussed.

  14. Vorticity vector-potential method based on time-dependent curvilinear coordinates for two-dimensional rotating flows in closed configurations

    NASA Astrophysics Data System (ADS)

    Fu, Yuan; Zhang, Da-peng; Xie, Xi-lin

    2018-03-01

    In this study, a vorticity vector-potential method for two-dimensional viscous incompressible rotating driven flows is developed in the time-dependent curvilinear coordinates. The method is applicable in both inertial and non-inertial frames of reference with the advantage of a fixed and regular calculation domain. The numerical method is applied to triangle and curved triangle configurations in constant and varying rotational angular velocity cases respectively. The evolutions of flow field are studied. The geostrophic effect, unsteady effect and curvature effect on the evolutions are discussed.

  15. Differential roles of two delayed rectifier potassium currents in regulation of ventricular action potential duration and arrhythmia susceptibility.

    PubMed

    Devenyi, Ryan A; Ortega, Francis A; Groenendaal, Willemijn; Krogh-Madsen, Trine; Christini, David J; Sobie, Eric A

    2017-04-01

    Arrhythmias result from disruptions to cardiac electrical activity, although the factors that control cellular action potentials are incompletely understood. We combined mathematical modelling with experiments in heart cells from guinea pigs to determine how cellular electrical activity is regulated. A mismatch between modelling predictions and the experimental results allowed us to construct an improved, more predictive mathematical model. The balance between two particular potassium currents dictates how heart cells respond to perturbations and their susceptibility to arrhythmias. Imbalances of ionic currents can destabilize the cardiac action potential and potentially trigger lethal cardiac arrhythmias. In the present study, we combined mathematical modelling with information-rich dynamic clamp experiments to determine the regulation of action potential morphology in guinea pig ventricular myocytes. Parameter sensitivity analysis was used to predict how changes in ionic currents alter action potential duration, and these were tested experimentally using dynamic clamp, a technique that allows for multiple perturbations to be tested in each cell. Surprisingly, we found that a leading mathematical model, developed with traditional approaches, systematically underestimated experimental responses to dynamic clamp perturbations. We then re-parameterized the model using a genetic algorithm, which allowed us to estimate ionic current levels in each of the cells studied. This unbiased model adjustment consistently predicted an increase in the rapid delayed rectifier K + current and a drastic decrease in the slow delayed rectifier K + current, and this prediction was validated experimentally. Subsequent simulations with the adjusted model generated the clinically relevant prediction that the slow delayed rectifier is better able to stabilize the action potential and suppress pro-arrhythmic events than the rapid delayed rectifier. In summary, iterative coupling of

  16. Human action classification using procrustes shape theory

    NASA Astrophysics Data System (ADS)

    Cho, Wanhyun; Kim, Sangkyoon; Park, Soonyoung; Lee, Myungeun

    2015-02-01

    In this paper, we propose new method that can classify a human action using Procrustes shape theory. First, we extract a pre-shape configuration vector of landmarks from each frame of an image sequence representing an arbitrary human action, and then we have derived the Procrustes fit vector for pre-shape configuration vector. Second, we extract a set of pre-shape vectors from tanning sample stored at database, and we compute a Procrustes mean shape vector for these preshape vectors. Third, we extract a sequence of the pre-shape vectors from input video, and we project this sequence of pre-shape vectors on the tangent space with respect to the pole taking as a sequence of mean shape vectors corresponding with a target video. And we calculate the Procrustes distance between two sequences of the projection pre-shape vectors on the tangent space and the mean shape vectors. Finally, we classify the input video into the human action class with minimum Procrustes distance. We assess a performance of the proposed method using one public dataset, namely Weizmann human action dataset. Experimental results reveal that the proposed method performs very good on this dataset.

  17. Action potentials and amphetamine release antipsychotic drug from dopamine neuron synaptic VMAT vesicles.

    PubMed

    Tucker, Kristal R; Block, Ethan R; Levitan, Edwin S

    2015-08-11

    Based on lysotracker red imaging in cultured hippocampal neurons, antipsychotic drugs (APDs) were proposed to accumulate in synaptic vesicles by acidic trapping and to be released in response to action potentials. Because many APDs are dopamine (DA) D2 receptor (D2R) antagonists, such a mechanism would be particularly interesting if it operated in midbrain DA neurons. Here, the APD cyamemazine (CYAM) is visualized directly by two-photon microscopy in substantia nigra and striatum brain slices. CYAM accumulated slowly into puncta based on vacuolar H(+)-ATPase activity and dispersed rapidly upon dissipating organelle pH gradients. Thus, CYAM is subject to acidic trapping and released upon deprotonation. In the striatum, Ca(2+)-dependent reduction of the CYAM punctate signal was induced by depolarization or action potentials. Striatal CYAM overlapped with the dopamine transporter (DAT). Furthermore, parachloroamphetamine (pCA), acting via vesicular monoamine transporter (VMAT), and a charged VMAT, substrate 1-methyl-4-phenylpyridinium (MPP(+)), reduced striatal CYAM. In vivo CYAM administration and in vitro experiments confirmed that clinically relevant CYAM concentrations result in vesicular accumulation and pCA-dependent release. These results show that some CYAM is in DA neuron VMAT vesicles and suggests a new drug interaction in which amphetamine induces CYAM deprotonation and release as a consequence of the H(+) countertransport by VMAT that accompanies vesicular uptake, but not by inducing exchange or acting as a weak base. Therefore, in the striatum, APDs are released with DA in response to action potentials and an amphetamine. This synaptic corelease is expected to enhance APD antagonism of D2Rs where and when dopaminergic transmission occurs.

  18. Properties of Ca2+ sparks evoked by action potentials in mouse ventricular myocytes

    PubMed Central

    Bridge, John H B; Ershler, Philip R; Cannell, Mark B

    1999-01-01

    Calcium sparks were examined in enzymatically dissociated mouse cardiac ventricular cells using the calcium indicator fluo-3 and confocal microscopy. The properties of the mouse cardiac calcium spark are generally similar to those reported for other species.Examination of the temporal relationship between the action potential and the time course of calcium spark production showed that calcium sparks are more likely to occur during the initial repolarization phase of the action potential. The latency of their occurrence varied by less than 1·4 ms (s.d.) and this low variability may be explained by the interaction of the gating of L-type calcium channels with the changes in driving force for calcium entry during the action potential.When fixed sites within the cell are examined, calcium sparks have relatively constant amplitude but the amplitude of the sparks was variable among sites. The low variability of the amplitude of the calcium sparks suggests that more than one sarcoplasmic reticulum (SR) release channel must be involved in their genesis. Noise analysis (with the assumption of independent gating) suggests that > 18 SR calcium release channels may be involved in the generation of the calcium spark. At a fixed site, the response is close to ‘all-or-none’ behaviour which suggests that calcium sparks are indeed elementary events underlying cardiac excitation-contraction coupling.A method for selecting spark sites for signal averaging is presented which allows the time course of the spark to be examined with high temporal and spatial resolution. Using this method we show the development of the calcium spark at high signal-to-noise levels. PMID:10381593

  19. Improvement on the Repair Effect of Electrochemical Chloride Extraction Using a Modified Electrode Configuration

    PubMed Central

    Feng, Wei; Xu, Jinxia; Jiang, Linhua; Song, Yingbin; Cao, Yalong; Tan, Qiping

    2018-01-01

    To improve the repair effect of electrochemical chloride extraction, a modified electrode configuration is applied in this investigation. In this configuration, two auxiliary electrodes placed in the anodic and cathodic electrolytes were used as the anode and cathode, respectively. Besides this, the steel in the mortar was grounded to protect it from corrosion. By a comparative experiment, the potential evolution, various ions concentrations (Cl−, OH−, Na+, and K+) in different mortar depths, the corrosion potential, and the current density of the steel were measured. The results indicate that compared to electrochemical chloride extraction with the traditional electrode configuration, this electrochemical chloride extraction method with a modified electrode configuration has a similar chloride removal ratio. Besides this, potential of steel is just about 800 mV for a saturated calomel electrode (SCE) during the treatment, which did not reach the hydrogen evolution potential. The phenomenon of the accumulation of OH−, Na+, and K+ did not occur when the modified electrode configuration is applied. Additionally, higher corrosion potentials and lower corrosion current rates were measured after performing electrochemical chloride extraction with the modified electrode configuration. Additionally, it is a short period of time for the steel to go from activation to passivation. On this basis, the modified electrode configuration may overcome the drawbacks of electrochemical chloride extraction. PMID:29389855

  20. Molecular wave function and effective adiabatic potentials calculated by extended multi-configuration time-dependent Hartree-Fock method

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kato, Tsuyoshi; Ide, Yoshihiro; Yamanouchi, Kaoru

    We first calculate the ground-state molecular wave function of 1D model H{sub 2} molecule by solving the coupled equations of motion formulated in the extended multi-configuration time-dependent Hartree-Fock (MCTDHF) method by the imaginary time propagation. From the comparisons with the results obtained by the Born-Huang (BH) expansion method as well as with the exact wave function, we observe that the memory size required in the extended MCTDHF method is about two orders of magnitude smaller than in the BH expansion method to achieve the same accuracy for the total energy. Second, in order to provide a theoretical means to understandmore » dynamical behavior of the wave function, we propose to define effective adiabatic potential functions and compare them with the conventional adiabatic electronic potentials, although the notion of the adiabatic potentials is not used in the extended MCTDHF approach. From the comparison, we conclude that by calculating the effective potentials we may be able to predict the energy differences among electronic states even for a time-dependent system, e.g., time-dependent excitation energies, which would be difficult to be estimated within the BH expansion approach.« less

  1. Clinical significance of the summating potential-action potential ratio and the action potential latency difference for condensation and rarefaction clicks in Meniere's disease.

    PubMed

    Ohashi, Toru; Nishino, Hirohito; Arai, Yoko; Hyodo, Makoto; Takatsu, Mitsuharu

    2009-04-01

    This study was aimed to elucidate the diagnostic significance of the summating potential (SP)-action potential (AP) ratio and the AP latency difference between condensation and rarefaction clicks (AP con-rar difference) in Meniere's disease. The AP and SP were recorded transtympanically in 67 patients with definite Meniere's disease. The SP/AP ratio and the AP con-rar difference were assessed in terms of 1) their interrelationship, 2) their relationship to hearing level, and 3) the rate of occurrence of abnormal values according to the stages of Meniere's disease. No correlation was found between the SP/AP ratio and the AP con-rar difference. Neither the SP/AP ratio in general nor the AP con-rar difference was correlated with the hearing level. However, enhanced values of the SP/AP ratio (0.35 or higher) were moderately correlated with the hearing level (r = 0.51), and their occurrence rate was 55.2%. An increased AP con-rar difference (0.13 ms or longer) was not correlated with the hearing level, and its occurrence rate was 50.2%; it appeared most frequently at stage 3 (p <0.05). An enhanced SP/AP ratio might not always indicate the presence of endolymphatic hydrops associated with an increase in endolymphatic pressure. An increased AP con-rar difference might reflect the presence of a biased basilar membrane resulting from an increased endolymphatic pressure, and hence it is diagnostically essential to simultaneously evaluate the SP/AP ratio and the AP con-rar difference.

  2. Simultaneous recording of the action potential and its whole-cell associated ion current on NG108-15 cells cultured over a MWCNT electrode

    NASA Astrophysics Data System (ADS)

    Morales-Reyes, I.; Seseña-Rubfiaro, A.; Acosta-García, M. C.; Batina, N.; Godínez-Fernández, R.

    2016-08-01

    It is well known that, in excitable cells, the dynamics of the ion currents (I i) is extremely important to determine both the magnitude and time course of an action potential (A p). To observe these two processes simultaneously, we cultured NG108-15 cells over a multi-walled carbon nanotubes electrode (MWCNTe) surface and arranged a two independent Patch Clamp system configuration (Bi-Patch Clamp). The first system was used in the voltage or current clamp mode, using a glass micropipette as an electrode. The second system was modified to connect the MWCNTe to virtual ground. While the A p was recorded through the micropipette electrode, the MWCNTe was used to measure the underlying whole-cell current. This configuration allowed us to record both the membrane voltage (V m) and the current changes simultaneously. Images acquired by atomic force microscopy (AFM) and scanning electron microscopy (SEM) indicate that cultured cells developed a complex network of neurites, which served to establish the necessary close contact and strong adhesion to the MWCNTe surface. These features were a key factor to obtain the recording of the whole-cell I i with a high signal to noise ratio (SNR). The experimental results were satisfactorily reproduced by a theoretical model developed to simulate the proposed system. Besides the contribution to a better understanding of the fundamental mechanisms involved in cell communication, the developed method could be useful in cell physiology studies, pharmacology and diseases diagnosis.

  3. Action potentials recorded from bundles of very thin, gray matter axons in rat cerebellar slices using a grease-gap method.

    PubMed

    Palani, Damodharan; Pekala, Dobromila; Baginskas, Armantas; Szkudlarek, Hanna; Raastad, Morten

    2012-07-15

    We investigated the ability of a grease-gap method to record fast and slow changes of the membrane potential from bundles of gray matter axons. Their membrane potentials are of particular interest because these axons are different from most axons that have been investigated using intra-axonal or gap techniques. One of the main differences is that gray matter axons typically have closely spaced presynaptic specializations, called boutons or varicosities, distributed along their entire paths. In response to electrical activation of bundles of parallel fiber axons we were able to record small (128-416μV) but stable signals that we show most likely represented a fraction of the trans-membrane action potentials. A less-than 100% fraction prevents measurements of absolute values for membrane potentials, but the good signal-to-noise ratio (typically 10-16) allows detection of changes in resting membrane potential, action potentials and their after-potentials. Because very little is known about the shape of action potentials and after-potentials in these axons we used several independent methods to make it likely that the grease-gap signal was of intra-axonal origin. We demonstrate the utility of the method by showing that the action potentials in cerebellar parallel fibers and hippocampal Schaffer collaterals had a slowly decaying, depolarized after-potential. The method is ideal for pharmacological tests, which we demonstrate by showing that the slow after-potential was sensitive to 4-AP, and that the membrane potential was reduced by 200μM Ba(2+). Copyright © 2012 Elsevier B.V. All rights reserved.

  4. Carbon nanotube multi-electrode array chips for noninvasive real-time measurement of dopamine, action potentials, and postsynaptic potentials.

    PubMed

    Suzuki, Ikuro; Fukuda, Mao; Shirakawa, Keiichi; Jiko, Hideyasu; Gotoh, Masao

    2013-11-15

    Multi-electrode arrays (MEAs) can be used for noninvasive, real-time, and long-term recording of electrophysiological activity and changes in the extracellular chemical microenvironment. Neural network organization, neuronal excitability, synaptic and phenotypic plasticity, and drug responses may be monitored by MEAs, but it is still difficult to measure presynaptic activity, such as neurotransmitter release, from the presynaptic bouton. In this study, we describe the development of planar carbon nanotube (CNT)-MEA chips that can measure both the release of the neurotransmitter dopamine as well as electrophysiological responses such as field postsynaptic potentials (fPSPs) and action potentials (APs). These CNT-MEA chips were fabricated by electroplating the indium-tin oxide (ITO) microelectrode surfaces. The CNT-plated ITO electrode exhibited electrochemical response, having much higher current density compared with the bare ITO electrode. Chronoamperometric measurements using these CNT-MEA chips detected dopamine at nanomolar concentrations. By placing mouse striatal brain slices on the CNT-MEA chip, we successfully measured synaptic dopamine release from spontaneous firings with a high S/N ratio of 62. Furthermore, APs and fPSPs were measured from cultured hippocampal neurons and slices with high temporal resolution and a 100-fold greater S/N ratio. Our CNT-MEA chips made it possible to measure neurotransmitter dopamine (presynaptic activities), postsynaptic potentials, and action potentials, which have a central role in information processing in the neuronal network. CNT-MEA chips could prove useful for in vitro studies of stem cell differentiation, drug screening and toxicity, synaptic plasticity, and pathogenic processes involved in epilepsy, stroke, and neurodegenerative diseases. Copyright © 2013 Elsevier B.V. All rights reserved.

  5. Configuration aerodynamics

    NASA Technical Reports Server (NTRS)

    Polhamus, E. C.; Gloss, B. B.

    1981-01-01

    Static aerodynamic research related to aircraft configurations in their cruise or combat modes is discussed. Subsonic transport aircraft, transonic tactical aircraft, and slender wing aircraft are considered. The status and plans of Langley's NTF configuration research program are reviewed. Recommendations for near term configuration research are made.

  6. Flammability Configuration Analysis for Spacecraft Applications

    NASA Technical Reports Server (NTRS)

    Pedley, Michael D.

    2014-01-01

    Fire is one of the many potentially catastrophic hazards associated with the operation of crewed spacecraft. A major lesson learned by NASA from the Apollo 204 fire in 1966 was that ignition sources in an electrically powered vehicle should and can be minimized, but can never be eliminated completely. For this reason, spacecraft fire control is based on minimizing potential ignition sources and eliminating materials that can propagate fire. Fire extinguishers are always provided on crewed spacecraft, but are not considered as part of the fire control process. "Eliminating materials that can propagate fire" does not mean eliminating all flammable materials - the cost of designing and building spacecraft using only nonflammable materials is extraordinary and unnecessary. It means controlling the quantity and configuration of such materials to eliminate potential fire propagation paths and thus ensure that any fire would be small, localized, and isolated, and would self-extinguish without harm to the crew. Over the years, NASA has developed many solutions for controlling the configuration of flammable materials (and potentially flammable materials in commercial "off-the-shelf" hardware) so that they can be used safely in air and oxygen-enriched environments in crewed spacecraft. This document describes and explains these design solutions so payload customers and other organizations can use them in designing safe and cost-effective flight hardware. Proper application of these guidelines will produce acceptable flammability configurations for hardware located in any compartment of the International Space Station or other program crewed vehicles and habitats. However, use of these guidelines does not exempt hardware organizations of the responsibility for safety of the hardware under their control.

  7. An Excel-based implementation of the spectral method of action potential alternans analysis.

    PubMed

    Pearman, Charles M

    2014-12-01

    Action potential (AP) alternans has been well established as a mechanism of arrhythmogenesis and sudden cardiac death. Proper interpretation of AP alternans requires a robust method of alternans quantification. Traditional methods of alternans analysis neglect higher order periodicities that may have greater pro-arrhythmic potential than classical 2:1 alternans. The spectral method of alternans analysis, already widely used in the related study of microvolt T-wave alternans, has also been used to study AP alternans. Software to meet the specific needs of AP alternans analysis is not currently available in the public domain. An AP analysis tool is implemented here, written in Visual Basic for Applications and using Microsoft Excel as a shell. This performs a sophisticated analysis of alternans behavior allowing reliable distinction of alternans from random fluctuations, quantification of alternans magnitude, and identification of which phases of the AP are most affected. In addition, the spectral method has been adapted to allow detection and quantification of higher order regular oscillations. Analysis of action potential morphology is also performed. A simple user interface enables easy import, analysis, and export of collated results. © 2014 The Author. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

  8. Reactive species modify NaV1.8 channels and affect action potentials in murine dorsal root ganglia neurons

    PubMed Central

    Schink, Martin; Leipolcf, Enrico; Schirmeyer, Jana; Schönherr, Roland; Hoshi, Toshinori; Heinemann, Stefan H.

    2016-01-01

    Dorsal root ganglia (DRG) neurons are important relay stations between the periphery and the central nervous system and are essential for somatosensory signaling. Reactive species are produced in a variety of physiological and pathophysiological conditions and are known to alter electric signaling. Here we studied the influence of reactive species on the electrical properties of DRG neurons from mice with the whole-cell patch-clamp method. Even mild stress induced by either low concentrations of chloramine-T (10 µM) or low-intensity blue-light irradiation profoundly diminished action potential frequency but prolonged single action potentials in wild-type neurons. The impact on evoked action potentials was much smaller in neurons deficient of the tetrodotoxin (TTX)-resistant voltage-gated sodium channel NaV1.8 (NaV1.8−/−), the channel most important for the action potential upstroke in DRG neurons. Low concentrations of chloramine-T caused a significant reduction of NaV1.8 peak current and at higher concentrations progressively slowed down inactivation. Blue light had a smaller effect on amplitude but slowed down NaV1.8 channel inactivation. The observed effects were less apparent for TTX-sensitive NaV channels. NaV1.8 is an important reactive-species-sensitive component in the electrical signaling of DRG neurons, potentially giving rise to loss-of-function and gain-of-function phenomena depending on the type of reactive species and their effective concentration and time of exposure. PMID:26383867

  9. Reactive species modify NaV1.8 channels and affect action potentials in murine dorsal root ganglion neurons.

    PubMed

    Schink, Martin; Leipold, Enrico; Schirmeyer, Jana; Schönherr, Roland; Hoshi, Toshinori; Heinemann, Stefan H

    2016-01-01

    Dorsal root ganglion (DRG) neurons are important relay stations between the periphery and the central nervous system and are essential for somatosensory signaling. Reactive species are produced in a variety of physiological and pathophysiological conditions and are known to alter electric signaling. Here we studied the influence of reactive species on the electrical properties of DRG neurons from mice with the whole-cell patch-clamp method. Even mild stress induced by either low concentrations of chloramine-T (10 μM) or low-intensity blue light irradiation profoundly diminished action potential frequency but prolonged single action potentials in wild-type neurons. The impact on evoked action potentials was much smaller in neurons deficient of the tetrodotoxin (TTX)-resistant voltage-gated sodium channel NaV1.8 (NaV1.8(-/-)), the channel most important for the action potential upstroke in DRG neurons. Low concentrations of chloramine-T caused a significant reduction of NaV1.8 peak current and, at higher concentrations, progressively slowed down inactivation. Blue light had a smaller effect on amplitude but slowed down NaV1.8 channel inactivation. The observed effects were less apparent for TTX-sensitive NaV channels. NaV1.8 is an important reactive-species-sensitive component in the electrical signaling of DRG neurons, potentially giving rise to loss-of-function and gain-of-function phenomena depending on the type of reactive species and their effective concentration and time of exposure.

  10. Sprint training shortens prolonged action potential duration in postinfarction rat myocyte: mechanisms.

    PubMed

    Zhang, X Q; Zhang, L Q; Palmer, B M; Ng, Y C; Musch, T I; Moore, R L; Cheung, J Y

    2001-05-01

    Two electrophysiological manifestations of myocardial infarction (MI)-induced myocyte hypertrophy are prolongation of action potential duration (APD) and reduction of transient outward current (I(to)) density. Because high-intensity sprint training (HIST) ameliorated myocyte hypertrophy and improved myocyte Ca(2+) homeostasis and contractility after MI, the present study evaluated whether 6-8 wk of HIST would shorten the prolonged APD and improve the depressed I(to) in post-MI myocytes. There were no differences in resting membrane potential and action potential amplitude (APA) measured in myocytes isolated from sham-sedentary (Sed), MI-Sed, and MI-HIST groups. Times required for repolarization to 50 and 90% APA were significantly (P < 0.001) prolonged in MI-Sed myocytes. HIST reduced times required for repolarization to 50 and 90% APA to values observed in Sham-Sed myocytes. The fast and slow components of I(to) were significantly (P < 0.0001) reduced in MI-Sed myocytes. HIST significantly (P < 0.001) enhanced the fast and slow components of I(to) in MI myocytes, although not to levels observed in Sham-Sed myocytes. There were no significant differences in steady-state I(to) inactivation and activation parameters among Sham-Sed, MI-Sed, and MI-HIST myocytes. Likewise, recovery from time-dependent inactivation was also similar among the three groups. We suggest that normalization of APD after MI by HIST may be mediated by restoration of I(to) toward normal levels.

  11. Investigating a Potential Auxin-Related Mode of Hormetic/Inhibitory Action of the Phytotoxin Parthenin.

    PubMed

    Belz, Regina G

    2016-01-01

    Parthenin is a metabolite of Parthenium hysterophorus and is believed to contribute to the weed's invasiveness via allelopathy. Despite the potential of parthenin to suppress competitors, low doses stimulate plant growth. This biphasic action was hypothesized to be auxin-like and, therefore, an auxin-related mode of parthenin action was investigated using two approaches: joint action experiments with Lactuca sativa, and dose-response experiments with auxin/antiauxin-resistant Arabidopsis thaliana genotypes. The joint action approach comprised binary mixtures of subinhibitory doses of the auxin 3-indoleacetic acid (IAA) mixed with parthenin or one of three reference compounds [indole-3-butyric acid (IBA), 2,3,5-triiodobenzoic acid (TIBA), 2-(p-chlorophenoxy)-2-methylpropionic acid (PCIB)]. The reference compounds significantly interacted with IAA at all doses, but parthenin interacted only at low doses indicating that parthenin hormesis may be auxin-related, in contrast to its inhibitory action. The genetic approach investigated the response of four auxin/antiauxin-resistant mutants and a wildtype to parthenin or two reference compounds (IAA, PCIB). The responses of mutant plants to the reference compounds confirmed previous reports, but differed from the responses observed for parthenin. Parthenin stimulated and inhibited all mutants independent of resistance. This provided no indication for an auxin-related action of parthenin. Therefore, the hypothesis of an auxin-related inhibitory action of parthenin was rejected in two independent experimental approaches, while the hypothesis of an auxin-related stimulatory effect could not be rejected.

  12. Effects of phloretin and phloridzin on Ca2+ handling, the action potential, and ion currents in rat ventricular myocytes.

    PubMed

    Olson, Marnie L; Kargacin, Margaret E; Ward, Christopher A; Kargacin, Gary J

    2007-06-01

    The effects of the phytoestrogens phloretin and phloridzin on Ca(2+) handling, cell shortening, the action potential, and Ca(2+) and K(+) currents in freshly isolated cardiac myocytes from rat ventricle were examined. Phloretin increased the amplitude and area and decreased the rate of decline of electrically evoked Ca(2+) transients in the myocytes. These effects were accompanied by an increase in the Ca(2+) load of the sarcoplasmic reticulum, as determined by the area of caffeine-evoked Ca(2+) transients. An increase in the extent of shortening of the myocytes in response to electrically evoked action potentials was also observed in the presence of phloretin. To further examine possible mechanisms contributing to the observed changes in Ca(2+) handling and contractility, the effects of phloretin on the cardiac action potential and plasma membrane Ca(2+) and K(+) currents were examined. Phloretin markedly increased the action potential duration in the myocytes, and it inhibited the Ca(2+)-independent transient outward K(+) current (I(to)). The inwardly rectifying K(+) current, the sustained outward delayed rectifier K(+) current, and L-type Ca(2+) currents were not significantly different in the presence and absence of phloretin, nor was there any evidence that the Na(+)/Ca(2+) exchanger was affected. The effects of phloretin on Ca(2+) handling in the myocytes are consistent with its effects on I(to). Phloridzin did not significantly alter the amplitude or area of electrically evoked Ca(2+) transients in the myocytes, nor did it have detectable effects on the sarcoplasmic reticulum Ca(2+) load, cell shortening, or the action potential.

  13. Assessing potentially dangerous medical actions with the computer-based case simulation portion of the USMLE step 3 examination.

    PubMed

    Harik, Polina; Cuddy, Monica M; O'Donovan, Seosaimhin; Murray, Constance T; Swanson, David B; Clauser, Brian E

    2009-10-01

    The 2000 Institute of Medicine report on patient safety brought renewed attention to the issue of preventable medical errors, and subsequently specialty boards and the National Board of Medical Examiners were encouraged to play a role in setting expectations around safety education. This paper examines potentially dangerous actions taken by examinees during the portion of the United States Medical Licensing Examination Step 3 that is particularly well suited to evaluating lapses in physician decision making, the Computer-based Case Simulation (CCS). Descriptive statistics and a general linear modeling approach were used to analyze dangerous actions ordered by 25,283 examinees that completed CCS for the first time between November 2006 and January 2008. More than 20% of examinees ordered at least one dangerous action with the potential to cause significant patient harm. The propensity to order dangerous actions may vary across clinical cases. The CCS format may provide a means of collecting important information about patient-care situations in which examinees may be more likely to commit dangerous actions and the propensity of examinees to order dangerous tests and treatments.

  14. Direct-detection EPID dosimetry: investigation of a potential clinical configuration for IMRT verification.

    PubMed

    Vial, Philip; Gustafsson, Helen; Oliver, Lyn; Baldock, Clive; Greer, Peter B

    2009-12-07

    The routine use of electronic portal imaging devices (EPIDs) as dosimeters for radiotherapy quality assurance is complicated by the non-water equivalence of the EPID's dose response. A commercial EPID modified to a direct-detection configuration was previously demonstrated to provide water-equivalent dose response with d(max) solid water build-up and 10 cm solid water backscatter. Clinical implementation of the direct EPID (dEPID) requires a design that maintains the water-equivalent dose response, can be incorporated onto existing EPID support arms and maintains sufficient image quality for clinical imaging. This study investigated the dEPID dose response with different configurations of build-up and backscatter using varying thickness of solid water and copper. Field size output factors and beam profiles measured with the dEPID were compared with ionization chamber measurements of dose in water for both 6 MV and 18 MV. The dEPID configured with d(max) solid water build-up and no backscatter (except for the support arm) was within 1.5% of dose in water data for both energies. The dEPID was maintained in this configuration for clinical dosimetry and image quality studies. Close agreement between the dEPID and treatment planning system was obtained for an IMRT field with 98.4% of pixels within the field meeting a gamma criterion of 3% and 3 mm. The reduced sensitivity of the dEPID resulted in a poorer image quality based on quantitative (contrast-to-noise ratio) and qualitative (anthropomorphic phantom) studies. However, clinically useful images were obtained with the dEPID using typical treatment field doses. The dEPID is a water-equivalent dosimeter that can be implemented with minimal modifications to the standard commercial EPID design. The proposed dEPID design greatly simplifies the verification of IMRT dose delivery.

  15. A two-channel action-potential generator for testing neurophysiologic data acquisition/analysis systems.

    PubMed

    Lisiecki, R S; Voigt, H F

    1995-08-01

    A 2-channel action-potential generator system was designed for use in testing neurophysiologic data acquisition/analysis systems. The system consists of a personal computer controlling an external hardware unit. This system is capable of generating 2 channels of simulated action potential (AP) waveshapes. The AP waveforms are generated from the linear combination of 2 principal-component template functions. Each channel generates randomly occurring APs with a specified rate ranging from 1 to 200 events per second. The 2 trains may be independent of one another or the second channel may be made to be excited or inhibited by the events from the first channel with user-specified probabilities. A third internal channel may be made to excite or inhibit events in both of the 2 output channels with user-specified rate parameters and probabilities. The system produces voltage waveforms that may be used to test neurophysiologic data acquisition systems for recording from 2 spike trains simultaneously and for testing multispike-train analysis (e.g., cross-correlation) software.

  16. Traditional Japanese medicines inhibit compound action potentials in the frog sciatic nerve.

    PubMed

    Matsushita, Akitomo; Fujita, Tsugumi; Ohtsubo, Sena; Kumamoto, Eiichi

    2016-02-03

    Traditional Japanese (Kampo) medicines have a variety of clinical effects including pain alleviation, but evidence for a mechanism for their pain relief has not yet been elucidated fully. Considering that Kampo medicine contains many plant-derived chemicals having an ability to inhibit nerve action potential conduction, it is possible that this medicine inhibits nerve conduction. The purpose of the present study was to know how various Kampo medicines affect nerve conduction. We examined the effects of Kampo and crude medicines on compound action potentials (CAPs) recorded from the frog sciatic nerve by using the air-gap method. Daikenchuto, rikkosan, kikyoto, rikkunshito, shakuyakukanzoto and kakkonto concentration-dependently reduced the peak amplitude of the CAP. Among the Kampo medicines, daikenchuto was the most effective in inhibiting CAPs. Daikenchuto is composed of three kinds of crude medicine, Japanese pepper, processed ginger and ginseng radix. When the crude medicines were tested, Japanese pepper and processed ginger reduced CAP peak amplitudes, while ginseng radix hardly affected CAPs. Moreover, there was an interaction between the Japanese pepper and processed ginger activities in such that one medicine at low but not high concentrations increased the extent of the inhibition by the other one that was co-applied. Kampo medicines have an ability to inhibit nerve conduction. This action of daikenchuto is due to Japanese pepper and processed ginger but not ginseng radix, probably through an interaction between Japanese pepper and processed ginger in a manner dependent on their concentrations. Nerve conduction inhibition could contribute to at least a part of Kampo medicine's clinical effects such as pain alleviation. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  17. Heteromeric Kv7.2/7.3 Channels Differentially Regulate Action Potential Initiation and Conduction in Neocortical Myelinated Axons

    PubMed Central

    Battefeld, Arne; Tran, Baouyen T.; Gavrilis, Jason; Cooper, Edward C.

    2014-01-01

    Rapid energy-efficient signaling along vertebrate axons is achieved through intricate subcellular arrangements of voltage-gated ion channels and myelination. One recently appreciated example is the tight colocalization of Kv7 potassium channels and voltage-gated sodium (Nav) channels in the axonal initial segment and nodes of Ranvier. The local biophysical properties of these Kv7 channels and the functional impact of colocalization with Nav channels remain poorly understood. Here, we quantitatively examined Kv7 channels in myelinated axons of rat neocortical pyramidal neurons using high-resolution confocal imaging and patch-clamp recording. Kv7.2 and 7.3 immunoreactivity steeply increased within the distal two-thirds of the axon initial segment and was mirrored by the conductance density estimates, which increased from ∼12 (proximal) to 150 pS μm−2 (distal). The axonal initial segment and nodal M-currents were similar in voltage dependence and kinetics, carried by Kv7.2/7.3 heterotetramers, 4% activated at the resting membrane potential and rapidly activated with single-exponential time constants (∼15 ms at 28 mV). Experiments and computational modeling showed that while somatodendritic Kv7 channels are strongly activated by the backpropagating action potential to attenuate the afterdepolarization and repetitive firing, axonal Kv7 channels are minimally recruited by the forward-propagating action potential. Instead, in nodal domains Kv7.2/7.3 channels were found to increase Nav channel availability and action potential amplitude by stabilizing the resting membrane potential. Thus, Kv7 clustering near axonal Nav channels serves specific and context-dependent roles, both restraining initiation and enhancing conduction of the action potential. PMID:24599470

  18. Melatonin potentiates the anticonvulsant action of phenobarbital in neonatal rats.

    PubMed

    Forcelli, Patrick A; Soper, Colin; Duckles, Anne; Gale, Karen; Kondratyev, Alexei

    2013-12-01

    Phenobarbital is the most commonly utilized drug for neonatal seizures. However, questions regarding safety and efficacy of this drug make it particularly compelling to identify adjunct therapies that could boost therapeutic benefit. One potential adjunct therapy is melatonin. Melatonin is used clinically in neonatal and pediatric populations, and moreover, it exerts anticonvulsant actions in adult rats. However, it has not been previously evaluated for anticonvulsant effects in neonatal rats. Here, we tested the hypothesis that melatonin would exert anticonvulsant effects, either alone, or in combination with phenobarbital. Postnatal day (P)7 rats were treated with phenobarbital (0-40mg/kg) and/or melatonin (0-80mg/kg) prior to chemoconvulsant challenge with pentylenetetrazole (100mg/kg). We found that melatonin significantly potentiated the anticonvulsant efficacy of phenobarbital, but did not exert anticonvulsant effects on its own. These data provide additional evidence for the further examination of melatonin as an adjunct therapy in neonatal/pediatric epilepsy. Copyright © 2013 Elsevier B.V. All rights reserved.

  19. Melatonin potentiates the anticonvulsant action of phenobarbital in neonatal rats

    PubMed Central

    Forcelli, Patrick A.; Soper, Colin; Duckles, Anne; Gale, Karen; Kondratyev, Alexei

    2013-01-01

    Phenobarbital is the most commonly utilized drug for neonatal seizures. However, questions regarding safety and efficacy of this drug make it particularly compelling to identify adjunct therapies that could boost therapeutic benefit. One potential adjunct therapy is melatonin. Melatonin is used clinically in neonatal and pediatric populations, and moreover, it exerts anticonvulsant actions in adult rats. However, it has not been previously evaluated for anticonvulsant effects in neonatal rats. Here, we tested the hypothesis that melatonin would exert anticonvulsant effects, either alone, or in combination with phenobarbital, the most commonly utilized anticonvulsant in neonatal medicine. Postnatal day (P)7 rats were treated with phenobarbital (0–40 mg/kg) and/or melatonin (0–80 mg/kg) prior to chemoconvulsant challenge with pentylenetetrazole (100 mg/kg). We found that melatonin significantly potentiated the anticonvulsant efficacy of phenobarbital, but did not exert anticonvulsant effects on its own. These data provide additional evidence for the further examination of melatonin as an adjunct therapy in neonatal/pediatric epilepsy. PMID:24206906

  20. A multidimensional framework for assessing patient room configurations.

    PubMed

    Pati, Debajyoti; Harvey, Thomas E; Reyers, Evelyn; Evans, Jennie; Waggener, Laurie; Serrano, Marjorie; Saucier, Rachel; Nagle, Tina

    2009-01-01

    A framework for multidimensional assessment of patient room configurations is presented. Twenty-three issues are considered and categorized under six domains of assessment: (1) patient safety, (2) staff efficiency, (3) circulation, (4) infection control, (5) patient considerations, and (6) family amenities. Use of the framework to rank issues by importance and assess six alternative patient room configurations by a diverse group of experts in a symposium is described. One of the key questions posed during inpatient room design is the location of the bathroom. What issues are affected by the variations in room configuration that arise from bathroom location? A complete articulation of the issues that potentially are affected by room configuration is not available in the literature. The list of issues was developed by the authors in preparation for a symposium. The symposium was organized in May 2007 and attended by 14 experts from four institutions. Six alternative room configurations were used. Variations in the configurations included: (1) three same-handed and three mirror-image rooms; (2) three outboard, two inboard, and one nested bathroom; and (3) three rooms with footwall bathrooms and three with headwall bathrooms. In a four-step process, the attendees ranked the issues, discussed them in detail, rated each room configuration against each issue on a seven-point suitability scale, and conducted an overall assessment of the six configurations. Based on the ratings and rankings provided by the symposium participants, outboard bathroom locations were found to be most suitable, followed by nested and inboard configurations. Furthermore, configurations with patient bathrooms located on the footwall were rated as more suitable than headwall locations. The authors recommend, however, that the framework be used to determine a suitable room configuration in a specific context, rather than to identify configurations that will perform well universally.

  1. Monophasic action potentials of right atrium and electrophysiological properties of AV conducting system in patients with hypothyroidism.

    PubMed Central

    Gavrilescu, S; Luca, C; Streian, C; Lungu, G; Deutsch, G

    1976-01-01

    In 12 patients with manifest hypothyroidism right atrial monophasic action potentials showed a significant prolongation in comparison with data from normal or euthyroid patients. Atrial effective refractory periods were also significantly prolonged. After thyroid treatment the monophasic action potential duration and the effective refractory period of the right atrium were within normal ranges. In 6 hypothyroid patients studies of AV conduction with the aid of His bundle electrography and atrial pacing showed a supraHisian conduction delay which was manifest in one case and latent in another two. InfraHisian conduction delay was encountered in 2 cases. PMID:1008978

  2. Amphetamine Augments Action Potential-Dependent Dopaminergic Signaling in the Striatum in Vivo

    PubMed Central

    Ramsson, Eric S.; Covey, Daniel P.; Daberkow, David P.; Litherland, Melissa T.; Juliano, Steven A.; Garris, Paul A.

    2011-01-01

    Amphetamine (AMPH) is thought to disrupt normal patterns of action potential-dependent dopaminergic signaling by depleting dopamine (DA) vesicular stores and promoting non-exocytotic DA efflux. Voltammetry in brain slices concurrently demonstrates these key drug effects, along with competitive inhibition of neuronal DA uptake. Here we perform comparable kinetic and voltammetric analyses in vivo to determine whether AMPH acts qualitatively and quantitatively similar in the intact brain. Fast-scan cyclic voltammetry measured extracellular DA in dorsal and ventral striata of urethane-anesthetized rats. Electrically evoked recordings were analyzed to determine Km and Vmax for DA uptake and vesicular DA release, while background voltammetric current indexed basal DA concentration. AMPH (0.5, 3, and 10 mg/kg i.p.) robustly increased evoked DA responses in both striatal subregions. The predominant contributor to these elevated levels was competitive uptake inhibition, as exocytotic release was unchanged in the ventral striatum and only modestly decreased in the dorsal striatum. Increases in basal DA levels were not detected. These results are consistent with AMPH augmenting action potential-dependent dopaminergic signaling in vivo across a wide, behaviorally relevant dose range. Future work should be directed at possible causes for the distinct in vitro and in vivo pharmacology of AMPH. PMID:21443523

  3. K(ATP) channel blocker HMR 1883 reduces monophasic action potential shortening during coronary ischemia in anesthetised pigs.

    PubMed

    Wirth, K J; Uhde, J; Rosenstein, B; Englert, H C; Gögelein, H; Schölkens, B A; Busch, A E

    2000-02-01

    ATP-sensitive potassium channels (KATP) open during myocardial ischemia. The ensuing repolarising potassium efflux shortens the action potential. Accumulation of extracellular potassium is able to partially depolarise the membrane, reducing the upstroke velocity of the action potential and thereby impairing impulse conduction. Both mechanisms are believed to be involved in the development of reentrant arrhythmias during cardiac ischemia. The sulfonylthiourea HMR 1883 (1-[[5-[2-(5-chloro-O-anisamido)ethyl]-methoxyphenyl]sulfonyl]-3-m ethylthiourea) was designed as a cardioselective KATP channel blocker for the prevention of arrhythmic sudden death in patients with ischemic heart disease. The aim of this study was to show that this compound, which has already shown antifibrillatory efficacy in dogs and rats, is able to inhibit ischemic changes of the action potential induced by coronary artery occlusion in anesthetised pigs. Action potentials were taken in situ with the technique of monophasic action potential (MAP) recording. In a control group (n=7), three consecutive occlusions of a small branch of the left circumflex coronary artery resulted in reproducible reductions in MAP duration and a decrease in upstroke velocity. In a separate group (n=7), HMR 1883 (3 mg/kg i.v.) significantly (P<0.05) reduced the ischemia-induced shortening of the MAP: during the first and second control occlusion of the coronary artery in the HMR 1883-group, MAP50 duration shortened from 218.5 +/- 3.0 ms to 166.7 +/- 3.3 ms and from 219.7 +/- 4.5 ms to 164.9 +/- 1.8 ms, respectively. After HMR 1883, during the third occlusion, MAP duration decreased from 226.9 +/- 3.6 ms to 205.3 +/- 4.3 ms only corresponding to 59% inhibition. HMR 1883 also improved the upstroke velocity of the MAP, which was depressed by ischemia: in the two preceding control occlusions ischemia prolonged the time to peak of the MAP, an index for upstroke velocity, from 10.83 +/- 0.43 ms to 39.42 +/- 1.60 ms and from

  4. Tracking individual action potentials throughout mammalian axonal arbors.

    PubMed

    Radivojevic, Milos; Franke, Felix; Altermatt, Michael; Müller, Jan; Hierlemann, Andreas; Bakkum, Douglas J

    2017-10-09

    Axons are neuronal processes specialized for conduction of action potentials (APs). The timing and temporal precision of APs when they reach each of the synapses are fundamentally important for information processing in the brain. Due to small diameters of axons, direct recording of single AP transmission is challenging. Consequently, most knowledge about axonal conductance derives from modeling studies or indirect measurements. We demonstrate a method to noninvasively and directly record individual APs propagating along millimeter-length axonal arbors in cortical cultures with hundreds of microelectrodes at microsecond temporal resolution. We find that cortical axons conduct single APs with high temporal precision (~100 µs arrival time jitter per mm length) and reliability: in more than 8,000,000 recorded APs, we did not observe any conduction or branch-point failures. Upon high-frequency stimulation at 100 Hz, successive became slower, and their arrival time precision decreased by 20% and 12% for the 100th AP, respectively.

  5. The Influence of Glutamate on Axonal Compound Action Potential In Vitro.

    PubMed

    Abouelela, Ahmed; Wieraszko, Andrzej

    2016-01-01

    Background  Our previous experiments demonstrated modulation of the amplitude of the axonal compound action potential (CAP) by electrical stimulation. To verify assumption that glutamate released from axons could be involved in this phenomenon, the modification of the axonal CAP induced by glutamate was investigated. Objectives  The major objective of this research is to verify the hypothesis that axonal activity would trigger the release of glutamate, which in turn would interact with specific axonal receptors modifying the amplitude of the action potential. Methods  Segments of the sciatic nerve were exposed to exogenous glutamate in vitro, and CAP was recorded before and after glutamate application. In some experiments, the release of radioactive glutamate analog from the sciatic nerve exposed to exogenous glutamate was also evaluated. Results  The glutamate-induced increase in CAP was blocked by different glutamate receptor antagonists. The effect of glutamate was not observed in Ca-free medium, and was blocked by antagonists of calcium channels. Exogenous glutamate, applied to the segments of sciatic nerve, induced the release of radioactive glutamate analog, demonstrating glutamate-induced glutamate release. Immunohistochemical examination revealed that axolemma contains components necessary for glutamatergic neurotransmission. Conclusion  The proteins of the axonal membrane can under the influence of electrical stimulation or exogenous glutamate change membrane permeability and ionic conductance, leading to a change in the amplitude of CAP. We suggest that increased axonal activity leads to the release of glutamate that results in changes in the amplitude of CAPs.

  6. Iridium Oxide Nanotube Electrodes for Highly Sensitive and Prolonged Intracellular Measurement of Action Potentials

    PubMed Central

    Lin, Ziliang Carter; Xie, Chong; Osakada, Yasuko; Cui, Yi; Cui, Bianxiao

    2014-01-01

    Intracellular recording of action potentials is important to understand electrically-excitable cells. Recently, vertical nanoelectrodes have been developed to achieve highly sensitive, minimally invasive, and large scale intracellular recording. It has been demonstrated that the vertical geometry is crucial for the enhanced signal detection. Here we develop nanoelectrodes made up of nanotubes of iridium oxide. When cardiomyocytes are cultured upon those nanotubes, the cell membrane not only wraps around the vertical tubes but also protrudes deep into the hollow center. We show that this geometry enhances cell-electrode coupling and results in measuring much larger intracellular action potentials. The nanotube electrodes afford much longer intracellular access and are minimally invasive, making it possible to achieve stable recording up to an hour in a single session and more than 8 days of consecutive daily recording. This study suggests that the electrode performance can be significantly improved by optimizing the electrode geometry. PMID:24487777

  7. Oxidative shift in tissue redox potential increases beat-to-beat variability of action potential duration.

    PubMed

    Kistamás, Kornél; Hegyi, Bence; Váczi, Krisztina; Horváth, Balázs; Bányász, Tamás; Magyar, János; Szentandrássy, Norbert; Nánási, Péter P

    2015-07-01

    Profound changes in tissue redox potential occur in the heart under conditions of oxidative stress frequently associated with cardiac arrhythmias. Since beat-to-beat variability (short term variability, SV) of action potential duration (APD) is a good indicator of arrhythmia incidence, the aim of this work was to study the influence of redox changes on SV in isolated canine ventricular cardiomyocytes using a conventional microelectrode technique. The redox potential was shifted toward a reduced state using a reductive cocktail (containing dithiothreitol, glutathione, and ascorbic acid) while oxidative changes were initiated by superfusion with H2O2. Redox effects were evaluated as changes in "relative SV" determined by comparing SV changes with the concomitant APD changes. Exposure of myocytes to the reductive cocktail decreased SV significantly without any detectable effect on APD. Application of H2O2 increased both SV and APD, but the enhancement of SV was the greater, so relative SV increased. Longer exposure to H2O2 resulted in the development of early afterdepolarizations accompanied by tremendously increased SV. Pretreatment with the reductive cocktail prevented both elevation in relative SV and the development of afterdepolarizations. The results suggest that the increased beat-to-beat variability during an oxidative stress contributes to the generation of cardiac arrhythmias.

  8. EMIR: a configurable hierarchical system for event monitoring and incident response

    NASA Astrophysics Data System (ADS)

    Deich, William T. S.

    2014-07-01

    The Event Monitor and Incident Response system (emir) is a flexible, general-purpose system for monitoring and responding to all aspects of instrument, telescope, and general facility operations, and has been in use at the Automated Planet Finder telescope for two years. Responses to problems can include both passive actions (e.g. generating alerts) and active actions (e.g. modifying system settings). Emir includes a monitor-and-response daemon, plus graphical user interfaces and text-based clients that automatically configure themselves from data supplied at runtime by the daemon. The daemon is driven by a configuration file that describes each condition to be monitored, the actions to take when the condition is triggered, and how the conditions are aggregated into hierarchical groups of conditions. Emir has been implemented for the Keck Task Library (KTL) keyword-based systems used at Keck and Lick Observatories, but can be readily adapted to many event-driven architectures. This paper discusses the design and implementation of Emir , and the challenges in balancing the competing demands for simplicity, flexibility, power, and extensibility. Emir 's design lends itself well to multiple purposes, and in addition to its core monitor and response functions, it provides an effective framework for computing running statistics, aggregate values, and summary state values from the primitive state data generated by other subsystems, and even for creating quick-and-dirty control loops for simple systems.

  9. Remodelling of action potential and intracellular calcium cycling dynamics during subacute myocardial infarction promotes ventricular arrhythmias in Langendorff-perfused rabbit hearts

    PubMed Central

    Chou, Chung-Chuan; Zhou, Shengmei; Hayashi, Hideki; Nihei, Motoki; Liu, Yen-Bin; Wen, Ming-Shien; Yeh, San-Jou; Fishbein, Michael C; Weiss, James N; Lin, Shien-Fong; Wu, Delon; Chen, Peng-Sheng

    2007-01-01

    We hypothesize that remodelling of action potential and intracellular calcium (Cai) dynamics in the peri-infarct zone contributes to ventricular arrhythmogenesis in the postmyocardial infarction setting. To test this hypothesis, we performed simultaneous optical mapping of Cai and membrane potential (Vm) in the left ventricle in 15 rabbit hearts with myocardial infarction for 1 week. Ventricular premature beats frequently originated from the peri-infarct zone, and 37% showed elevation of Cai prior to Vm depolarization, suggesting reverse excitation–contraction coupling as their aetiology. During electrically induced ventricular fibrillation, the highest dominant frequency was in the peri-infarct zone in 61 of 70 episodes. The site of highest dominant frequency had steeper action potential duration restitution and was more susceptible to pacing-induced Cai alternans than sites remote from infarct. Wavebreaks during ventricular fibrillation tended to occur at sites of persistently elevated Cai. Infusion of propranolol flattened action potential duration restitution, reduced wavebreaks and converted ventricular fibrillation to ventricular tachycardia. We conclude that in the subacute phase of myocardial infarction, the peri-infarct zone exhibits regions with steep action potential duration restitution slope and unstable Cai dynamics. These changes may promote ventricular extrasystoles and increase the incidence of wavebreaks during ventricular fibrillation. Whereas increased tissue heterogeneity after subacute myocardial infarction creates a highly arrhythmogenic substrate, dynamic action potential and Cai cycling remodelling also contribute to the initiation and maintenance of ventricular fibrillation in this setting. PMID:17272354

  10. Heteromeric Kv7.2/7.3 channels differentially regulate action potential initiation and conduction in neocortical myelinated axons.

    PubMed

    Battefeld, Arne; Tran, Baouyen T; Gavrilis, Jason; Cooper, Edward C; Kole, Maarten H P

    2014-03-05

    Rapid energy-efficient signaling along vertebrate axons is achieved through intricate subcellular arrangements of voltage-gated ion channels and myelination. One recently appreciated example is the tight colocalization of K(v)7 potassium channels and voltage-gated sodium (Na(v)) channels in the axonal initial segment and nodes of Ranvier. The local biophysical properties of these K(v)7 channels and the functional impact of colocalization with Na(v) channels remain poorly understood. Here, we quantitatively examined K(v)7 channels in myelinated axons of rat neocortical pyramidal neurons using high-resolution confocal imaging and patch-clamp recording. K(v)7.2 and 7.3 immunoreactivity steeply increased within the distal two-thirds of the axon initial segment and was mirrored by the conductance density estimates, which increased from ~12 (proximal) to 150 pS μm(-2) (distal). The axonal initial segment and nodal M-currents were similar in voltage dependence and kinetics, carried by K(v)7.2/7.3 heterotetramers, 4% activated at the resting membrane potential and rapidly activated with single-exponential time constants (~15 ms at 28 mV). Experiments and computational modeling showed that while somatodendritic K(v)7 channels are strongly activated by the backpropagating action potential to attenuate the afterdepolarization and repetitive firing, axonal K(v)7 channels are minimally recruited by the forward-propagating action potential. Instead, in nodal domains K(v)7.2/7.3 channels were found to increase Na(v) channel availability and action potential amplitude by stabilizing the resting membrane potential. Thus, K(v)7 clustering near axonal Na(v) channels serves specific and context-dependent roles, both restraining initiation and enhancing conduction of the action potential.

  11. The Relative Influences of Phosphometabolites and pH on Action Potential Morphology during Myocardial Reperfusion: A Simulation Study

    PubMed Central

    Roberts, Byron N.; Christini, David J.

    2012-01-01

    Myocardial ischemia-reperfusion (IR) injury represents a constellation of pathological processes that occur when ischemic myocardium experiences a restoration of perfusion. Reentrant arrhythmias, which represent a particularly lethal manifestation of IR injury, can result when ischemic tissue exhibits decreased excitability and/or changes of action potential duration (APD), conditions that precipitate unidirectional conduction block. Many of the cellular components that are involved with IR injury are modulated by pH and/or phosphometabolites such as ATP and phosphocreatine (PCr), all of which can be manipulated in vivo and potentially in the clinical setting. Using a mathematical model of the cardiomyocyte that we previously developed to study ischemia and reperfusion, we performed a series of simulations with the aim of determining whether pH- or phosphometabolite-related processes play a more significant role in generating changes in excitability and action potential morphology that are associated with the development of reentry. In our simulations, persistent shortening of APD, action potential amplitude (APA), and depolarization of the resting membrane potential were more severe when ATP and PCr availability were suppressed during reperfusion than when extracellular pH recovery was inhibited. Reduced phosphometabolite availability and pH recovery affected multiple ion channels and exchangers. Some of these effects were the result of direct modulation by phosphometabolites and/or acidosis, while others resulted from elevated sodium and calcium loads during reperfusion. In addition, increasing ATP and PCr availability during reperfusion was more beneficial in terms of increasing APD and APA than was increasing the amount of pH recovery. Together, these results suggest that therapies directed at increasing ATP and/or PCr availability during reperfusion may be more beneficial than perturbing pH recovery with regard to mitigating action potential changes that

  12. Module Configuration

    DOEpatents

    Oweis, Salah; D'Ussel, Louis; Chagnon, Guy; Zuhowski, Michael; Sack, Tim; Laucournet, Gaullume; Jackson, Edward J.

    2002-06-04

    A stand alone battery module including: (a) a mechanical configuration; (b) a thermal management configuration; (c) an electrical connection configuration; and (d) an electronics configuration. Such a module is fully interchangeable in a battery pack assembly, mechanically, from the thermal management point of view, and electrically. With the same hardware, the module can accommodate different cell sizes and, therefore, can easily have different capacities. The module structure is designed to accommodate the electronics monitoring, protection, and printed wiring assembly boards (PWAs), as well as to allow airflow through the module. A plurality of modules may easily be connected together to form a battery pack. The parts of the module are designed to facilitate their manufacture and assembly.

  13. ParamAP: Standardized Parameterization of Sinoatrial Node Myocyte Action Potentials.

    PubMed

    Rickert, Christian; Proenza, Catherine

    2017-08-22

    Sinoatrial node myocytes act as cardiac pacemaker cells by generating spontaneous action potentials (APs). Much information is encoded in sinoatrial AP waveforms, but both the analysis and the comparison of AP parameters between studies is hindered by the lack of standardized parameter definitions and the absence of automated analysis tools. Here we introduce ParamAP, a standalone cross-platform computational tool that uses a template-free detection algorithm to automatically identify and parameterize APs from text input files. ParamAP employs a graphic user interface with automatic and user-customizable input modes, and it outputs data files in text and PDF formats. ParamAP returns a total of 16 AP waveform parameters including time intervals such as the AP duration, membrane potentials such as the maximum diastolic potential, and rates of change of the membrane potential such as the diastolic depolarization rate. ParamAP provides a robust AP detection algorithm in combination with a standardized AP parameter analysis over a wide range of AP waveforms and firing rates, owing in part to the use of an iterative algorithm for the determination of the threshold potential and the diastolic depolarization rate that is independent of the maximum upstroke velocity, a parameter that can vary significantly among sinoatrial APs. Because ParamAP is implemented in Python 3, it is also highly customizable and extensible. In conclusion, ParamAP is a powerful computational tool that facilitates quantitative analysis and enables comparison of sinoatrial APs by standardizing parameter definitions and providing an automated work flow. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  14. Rigid and flexible organic electrochemical transistor arrays for monitoring action potentials from electrogenic cells.

    PubMed

    Yao, Chunlei; Li, Qianqian; Guo, Jing; Yan, Feng; Hsing, I-Ming

    2015-03-11

    Rigid and flexible organic electrochemical transistor arrays are successfully implemented for monitoring cardiac action potentials. Excellent signal to noise ratios are achieved with values routinely larger than 4. These devices are promising to be used in both conventional and emerging areas. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Viewing Objects and Planning Actions: On the Potentiation of Grasping Behaviours by Visual Objects

    ERIC Educational Resources Information Center

    Makris, Stergios; Hadar, Aviad A.; Yarrow, Kielan

    2011-01-01

    How do humans interact with tools? Gibson (1979) suggested that humans perceive directly what tools afford in terms of meaningful actions. This "affordances" hypothesis implies that visual objects can potentiate motor responses even in the absence of an intention to act. Here we explore the temporal evolution of motor plans afforded by common…

  16. Interpolating moving least-squares methods for fitting potential energy surfaces: using classical trajectories to explore configuration space.

    PubMed

    Dawes, Richard; Passalacqua, Alessio; Wagner, Albert F; Sewell, Thomas D; Minkoff, Michael; Thompson, Donald L

    2009-04-14

    We develop two approaches for growing a fitted potential energy surface (PES) by the interpolating moving least-squares (IMLS) technique using classical trajectories. We illustrate both approaches by calculating nitrous acid (HONO) cis-->trans isomerization trajectories under the control of ab initio forces from low-level HF/cc-pVDZ electronic structure calculations. In this illustrative example, as few as 300 ab initio energy/gradient calculations are required to converge the isomerization rate constant at a fixed energy to approximately 10%. Neither approach requires any preliminary electronic structure calculations or initial approximate representation of the PES (beyond information required for trajectory initial conditions). Hessians are not required. Both approaches rely on the fitting error estimation properties of IMLS fits. The first approach, called IMLS-accelerated direct dynamics, propagates individual trajectories directly with no preliminary exploratory trajectories. The PES is grown "on the fly" with the computation of new ab initio data only when a fitting error estimate exceeds a prescribed tight tolerance. The second approach, called dynamics-driven IMLS fitting, uses relatively inexpensive exploratory trajectories to both determine and fit the dynamically accessible configuration space. Once exploratory trajectories no longer find configurations with fitting error estimates higher than the designated accuracy, the IMLS fit is considered to be complete and usable in classical trajectory calculations or other applications.

  17. Infants Recognize Similar Goals across Dissimilar Actions Involving Object Manipulation

    ERIC Educational Resources Information Center

    Olofson, Eric L.; Baldwin, Dare

    2011-01-01

    We investigated infants' ability to recognize the similarity between observed and implied goals when actions differed in surface-level motion details. In two experiments, 10- to 12-month-olds were habituated to an actor manipulating an object and then shown test actions in which the actor contacted the object with a novel hand configuration that…

  18. Magnetic configuration flexibility of snowflake divertor for HL-2M [Analysis of snowflake divertor configurations for HL-2M

    DOE PAGES

    Zheng, G. Y.; Xu, X. Q.; Ryutov, D. D.; ...

    2014-07-09

    HL-2M (Li, 2013 [1]) is a tokamak device that is under construction. Based on the magnetic coils design of HL-2M, four kinds of divertor configurations are calculated by CORSICA code (Pearlstein et al., 2001 [2]) with the same main plasma parameters, which are standard divertor, exact snowflake divertor, snowflake-plus divertor and snowflake-minus divertor configurations. The potential properties of these divertors are analyzed and presented in this paper: low poloidal field area around X-point, connection length from outside mid-plane to the primary X-point, target plate design and magnetic field shear. The results show that the snowflake configurations not only can reducemore » the heat load at divertor target plates, but also may improve the magneto-hydrodynamic stability by stronger magnetic shear at the edge. Furthermore, a new divertor configuration, named “tripod divertor”, is designed by adjusting the positions of the two X-points according to plasma parameters and magnetic coils current of HL-2M.« less

  19. Algorithm-enabled partial-angular-scan configurations for dual-energy CT.

    PubMed

    Chen, Buxin; Zhang, Zheng; Xia, Dan; Sidky, Emil Y; Pan, Xiaochuan

    2018-05-01

    We seek to investigate an optimization-based one-step method for image reconstruction that explicitly compensates for nonlinear spectral response (i.e., the beam-hardening effect) in dual-energy CT, to investigate the feasibility of the one-step method for enabling two dual-energy partial-angular-scan configurations, referred to as the short- and half-scan configurations, on standard CT scanners without involving additional hardware, and to investigate the potential of the short- and half-scan configurations in reducing imaging dose and scan time in a single-kVp-switch full-scan configuration in which two full rotations are made for collection of dual-energy data. We use the one-step method to reconstruct images directly from dual-energy data through solving a nonconvex optimization program that specifies the images to be reconstructed in dual-energy CT. Dual-energy full-scan data are generated from numerical phantoms and collected from physical phantoms with the standard single-kVp-switch full-scan configuration, whereas dual-energy short- and half-scan data are extracted from the corresponding full-scan data. Besides visual inspection and profile-plot comparison, the reconstructed images are analyzed also in quantitative studies based upon tasks of linear-attenuation-coefficient and material-concentration estimation and of material differentiation. Following the performance of a computer-simulation study to verify that the one-step method can reconstruct numerically accurately basis and monochromatic images of numerical phantoms, we reconstruct basis and monochromatic images by using the one-step method from real data of physical phantoms collected with the full-, short-, and half-scan configurations. Subjective inspection based upon visualization and profile-plot comparison reveals that monochromatic images, which are used often in practical applications, reconstructed from the full-, short-, and half-scan data are largely visually comparable except for some

  20. The real-time link between person perception and action: Brain potential evidence for dynamic continuity

    PubMed Central

    Freeman, Jonathan B.; Ambady, Nalini; Midgley, Katherine J.; Holcomb, Phillip J.

    2010-01-01

    Using event-related potentials, we investigated how the brain extracts information from another’s face and translates it into relevant action in real-time. In Study 1, participants made between-hand sex categorizations of sex-typical and sex-atypical faces. Sex-atypical faces evoked negativity between 250-550 ms (N300/N400 effects), reflecting the integration of accumulating sex-category knowledge into a coherent sex-category interpretation. Additionally, the lateralized readiness potential (LRP) revealed that the motor cortex began preparing for a correct hand response while social category knowledge was still gradually evolving in parallel. In Study 2, participants made between-hand eye-color categorizations as part of go/no-go trials that were contingent on a target’s sex. On no-go trials, although the hand did not actually move, information about eye color partially prepared the motor cortex to move the hand before perception of sex had finalized. Together, these findings demonstrate the dynamic continuity between person perception and action, such that ongoing results from face processing are immediately and continuously cascaded into the motor system over time. The preparation of action begins based on tentative perceptions of another’s face before perceivers have finished interpreting what they just saw. PMID:20602284

  1. The real-time link between person perception and action: brain potential evidence for dynamic continuity.

    PubMed

    Freeman, Jonathan B; Ambady, Nalini; Midgley, Katherine J; Holcomb, Phillip J

    2011-01-01

    Using event-related potentials, we investigated how the brain extracts information from another's face and translates it into relevant action in real time. In Study 1, participants made between-hand sex categorizations of sex-typical and sex-atypical faces. Sex-atypical faces evoked negativity between 250 and 550 ms (N300/N400 effects), reflecting the integration of accumulating sex-category knowledge into a coherent sex-category interpretation. Additionally, the lateralized readiness potential revealed that the motor cortex began preparing for a correct hand response while social category knowledge was still gradually evolving in parallel. In Study 2, participants made between-hand eye-color categorizations as part of go/no-go trials that were contingent on a target's sex. On no-go trials, although the hand did not actually move, information about eye color partially prepared the motor cortex to move the hand before perception of sex had finalized. Together, these findings demonstrate the dynamic continuity between person perception and action, such that ongoing results from face processing are immediately and continuously cascaded into the motor system over time. The preparation of action begins based on tentative perceptions of another's face before perceivers have finished interpreting what they just saw. © 2010 Psychology Press, an imprint of the Taylor & Francis Group, an Informa business

  2. Effects of astragaloside IV on action potentials and ionic currents in guinea-pig ventricular myocytes.

    PubMed

    Zhao, Meimi; Zhao, Jinsheng; He, Guilin; Sun, Xuefei; Huang, Xueshi; Hao, Liying

    2013-01-01

    Astragaloside IV (AS-IV) is one of the main active constituents of Astragalus membranaceus, which has various actions on the cardiovascular system. However, its electrophysiological mechanisms are not clear. In the present study, we investigated the effects of AS-IV on action potentials and membrane currents using the whole-cell patch clamp technique in isolated guinea-pig ventricular myocytes. AS-IV prolonged the action potential duration (APD) at all three tested concentrations. The peak effect was achieved with 1×10(-6) M, at which concentration AS-IV significantly prolonged the APD at 95% repolarization from 313.1±38.9 to 785.3±83.7 ms. AS-IV at 1×10(-6) M also enhanced the inward rectifier K(+) currents (I(K1)) and inhibited the delayed rectifier K(+) currents (I(K)). AS-IV (1×10(-6) M) strongly depressed the peak of voltage-dependent Ca(2+) channel current (I(CaL)) from -607.3±37.5 to -321.1±38.3 pA. However, AS-IV was not found to affect the Na(+) currents. Taken together, AS-IV prolonged APD of guinea-pig ventricular myocytes, which might be explained by its inhibition of I(K). AS-IV also influences Ca(2+) signaling through suppressing ICaL.

  3. Morphological Characterization of the Action Potential Initiation Segment in GnRH Neuron Dendrites and Axons of Male Mice.

    PubMed

    Herde, Michel K; Herbison, Allan E

    2015-11-01

    GnRH neurons are the final output neurons of the hypothalamic network controlling fertility in mammals. In the present study, we used ankyrin G immunohistochemistry and neurobiotin filling of live GnRH neurons in brain slices from GnRH-green fluorescent protein transgenic male mice to examine in detail the location of action potential initiation in GnRH neurons with somata residing at different locations in the basal forebrain. We found that the vast majority of GnRH neurons are bipolar in morphology, elaborating a thick (primary) and thinner (secondary) dendrite from opposite poles of the soma. In addition, an axon-like process arising predominantly from a proximal dendrite was observed in a subpopulation of GnRH neurons. Ankyrin G immunohistochemistry revealed the presence of a single action potential initiation zone ∼27 μm in length primarily in the secondary dendrite of GnRH neurons and located 30 to 140 μm distant from the cell soma, depending on the type of process and location of the cell body. In addition to dendrites, the GnRH neurons with cell bodies located close to hypothalamic circumventricular organs often elaborated ankyrin G-positive axon-like structures. Almost all GnRH neurons (>90%) had their action potential initiation site in a process that initially, or ultimately after a hairpin loop, was coursing in the direction of the median eminence. These studies indicate that action potentials are initiated in different dendritic and axonal compartments of the GnRH neuron in a manner that is dependent partly on the neuroanatomical location of the cell body.

  4. High-Bandwidth Atomic Force Microscopy Reveals A Mechanical spike Accompanying the Action Potential in mammalian Nerve Terminals

    NASA Astrophysics Data System (ADS)

    Salzberg, Brian M.

    2008-03-01

    Information transfer from neuron to neuron within nervous systems occurs when the action potential arrives at a nerve terminal and initiates the release of a chemical messenger (neurotransmitter). In the mammalian neurohypophysis (posterior pituitary), large and rapid changes in light scattering accompany secretion of transmitter-like neuropeptides. In the mouse, these intrinsic optical signals are intimately related to the arrival of the action potential (E-wave) and the release of arginine vasopressin and oxytocin (S-wave). We have used a high bandwidth (20 kHz) atomic force microscope (AFM) to demonstrate that these light scattering signals are associated with changes in nerve terminal volume, detected as nanometer-scale movements of a cantilever positioned on top of the neurohypophysis. The most rapid mechanical response, the ``spike'', has duration comparable to that of the action potential (˜2 ms) and probably reflects an increase in terminal volume due to H2O movement associated with Na^+-influx. Elementary calculations suggest that two H2O molecules accompanying each Na^+-ion could account for the ˜0.5-1.0 å increase in the diameter of each terminal during the action potential. Distinguishable from the mechanical ``spike'', a slower mechanical event, the ``dip'', represents a decrease in nerve terminal volume, depends upon Ca^2+-entry, as well as on intra-terminal Ca^2+-transients, and appears to monitor events associated with secretion. A simple hypothesis is that this ``dip'' reflects the extrusion of the dense core granule that comprises the secretory products. These dynamic high bandwidth AFM recordings are the first to monitor mechanical events in nervous systems and may provide novel insights into the mechanism(s) by which excitation is coupled to secretion at nerve terminals.

  5. TranAir: A full-potential, solution-adaptive, rectangular grid code for predicting subsonic, transonic, and supersonic flows about arbitrary configurations. User's manual

    NASA Technical Reports Server (NTRS)

    Johnson, F. T.; Samant, S. S.; Bieterman, M. B.; Melvin, R. G.; Young, D. P.; Bussoletti, J. E.; Hilmes, C. L.

    1992-01-01

    The TranAir computer program calculates transonic flow about arbitrary configurations at subsonic, transonic, and supersonic freestream Mach numbers. TranAir solves the nonlinear full potential equations subject to a variety of boundary conditions modeling wakes, inlets, exhausts, porous walls, and impermeable surfaces. Regions with different total temperature and pressure can be represented. The user's manual describes how to run the TranAir program and its graphical support programs.

  6. Configuration development study of the X-24C hypersonic research airplane, phase 2

    NASA Technical Reports Server (NTRS)

    Combs, H. G.

    1977-01-01

    The X-24C Hypersonic Research Vehicle, configured with a heat-sink structure, a launch mass limit of 31.75 Mg and powered by an LR-105 Rocket Engine plus 12 LR-101 Sustainer Engines, was found to be the more cost effective of the candidate configurations. In addition, the configuration provides the maximum off design growth potential capability and subsequently, was selected as the candidate configuration to be subjected to the design refinement study in the remaining segment of the study. Selection of this configuration was based on the analytical study conducted on the performance growth capabilities of the candidate configurations selected from the Phase 1 Study.

  7. Fluctuations of the gluon distribution from the small- x effective action

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Dumitru, Adrian; Skokov, Vladimir

    The computation of observables in high-energy QCD involves an average over stochastic semiclassical small-x gluon fields. The weight of various configurations is determined by the effective action. We introduce a method to study fluctuations of observables, functionals of the small-x fields, which does not explicitly involve dipoles. We integrate out those fluctuations of the semiclassical gluon field under which a given observable is invariant. Thereby we obtain the effective potential for that observable describing its fluctuations about the average. Here, we determine explicitly the effective potential for the covariant gauge gluon distribution both for the McLerran-Venugopalan (MV) model and formore » a (nonlocal) Gaussian approximation for the small-x effective action. This provides insight into the correlation of fluctuations of the number of hard gluons versus their typical transverse momentum. We find that the spectral shape of the fluctuations of the gluon distribution is fundamentally different in the MV model, where there is a pileup of gluons near the saturation scale, versus the solution of the small-x JIMWLK renormalization group, which generates essentially scale-invariant fluctuations above the absorptive boundary set by the saturation scale.« less

  8. Fluctuations of the gluon distribution from the small- x effective action

    DOE PAGES

    Dumitru, Adrian; Skokov, Vladimir

    2017-09-29

    The computation of observables in high-energy QCD involves an average over stochastic semiclassical small-x gluon fields. The weight of various configurations is determined by the effective action. We introduce a method to study fluctuations of observables, functionals of the small-x fields, which does not explicitly involve dipoles. We integrate out those fluctuations of the semiclassical gluon field under which a given observable is invariant. Thereby we obtain the effective potential for that observable describing its fluctuations about the average. Here, we determine explicitly the effective potential for the covariant gauge gluon distribution both for the McLerran-Venugopalan (MV) model and formore » a (nonlocal) Gaussian approximation for the small-x effective action. This provides insight into the correlation of fluctuations of the number of hard gluons versus their typical transverse momentum. We find that the spectral shape of the fluctuations of the gluon distribution is fundamentally different in the MV model, where there is a pileup of gluons near the saturation scale, versus the solution of the small-x JIMWLK renormalization group, which generates essentially scale-invariant fluctuations above the absorptive boundary set by the saturation scale.« less

  9. Compound Motor Action Potential Quantifies Recurrent Laryngeal Nerve Innervation in a Canine Model.

    PubMed

    Bhatt, Neel K; Park, Andrea M; Al-Lozi, Muhammad; Paniello, Randal C

    2016-07-01

    The compound motor action potential (CMAP) is the summated action potential from multiple muscle fibers activated by a single nerve impulse. The utility of laryngeal muscle CMAP for quantifying innervation following recurrent laryngeal nerve (RLN) injury was investigated. In a series of 21 canine hemi-laryngeal preparations, RLNs were exposed and a stimulating electrode placed. Maximum CMAP amplitudes and area under the curve from the thyroarytenoid (TA) muscles were obtained at baseline and at 6 months following injury to the RLN. Injury mechanisms included crush, stretch, cautery, and complete transection with microsuture repair. Prior to injury, baseline CMAP amplitudes and area under the curve were 15.81 mV and 15.49mVms, respectively. Six months following injury, CMAP amplitude and area under curve were 105.1% and 102.1% of baseline for stretch, 98.7% and 112.7% for crush, 93.3% and 114.3% for cautery. The CMAP amplitude and area under the curve in the transection/repair group had a 54.3% and 69.4% recovery, respectively, which were significantly different than baseline (P < .01, P < .05). These values were correlated with vocal fold motion. The CMAP is a measure of vocal fold innervation. The technique could be further developed for clinical and experimental applications. © The Author(s) 2016.

  10. [Effects of 2-(p-dimethylaminostyryl) pyridine methycholide (DSPM-Ci) on ECG, left atrium contractivity and on papillary muscle action potentials].

    PubMed

    Jiang, X Y; Zhou, C M; Li, D M; Zhang, K J

    1996-01-01

    The effects of DSPM-Cl on ECG in rats, on the dose-effect curve in guinea pig left atria and on the fast action potential (AP), high-K+ depolarized slow action potential (SAP) in guinea pigs papillary muscle were examined electrophysiologically. DSPM-Cl (2 mg.kg-1) showed significant nagative frequency, negative conductivity effect, and prolonged the PP and PR interval. DSPM-CI (30-50 mumol.L-1) was shown to inhibit left atria contractility and shift the concentration-response curve of Iso and CaCl2 to the right with PD2' values of 4.60 and 4.13, respectively. In addition, DSPM-Cl was found to prolong the duration of action potential 90 (APD90) and effective refractory period (ERP), and decrease the maximal upstroke velocity (Vmax) in K(+)-depolarized guinea pigs papillary muscles. The results suggest that, like verpamil, DSPM-Cl might be a calcium antagonist.

  11. Institutional Approaches to Innovation and Change (II): The Configurational Perspective on Institution Building.

    ERIC Educational Resources Information Center

    Bhola, H. S.

    Institution building is considered as a process amenable to both explanation and design if a generic "grammar of artifactual action" is used. The Configurational Theory of Innovation Diffusion model (CLER) is introduced and used to demonstrate how the world of the institution builder could be ordered as part of such grammar for designing…

  12. The Transformative Potential of Action Research and ICT in the Second Language (L2) Classroom

    ERIC Educational Resources Information Center

    Farren, Margaret; Crotty, Yvonne; Kilboy, Laura

    2015-01-01

    This study shows the transformative potential of action research and information and communications technology (ICT) in the second language (L2) classroom. Two enquiries from teacher-researchers are detailed in the article. Their engagement in a collaborative professional development Masters programme was pivotal in designing and implementing ICT…

  13. Action Potentials Initiate in the Axon Initial Segment and Propagate Through Axon Collaterals Reliably in Cerebellar Purkinje Neurons

    PubMed Central

    Foust, Amanda; Popovic, Marko; Zecevic, Dejan; McCormick, David A.

    2010-01-01

    Purkinje neurons are the output cells of the cerebellar cortex and generate spikes in two distinct modes, known as simple and complex spikes. Revealing the point of origin of these action potentials, and how they conduct into local axon collaterals, is important for understanding local and distal neuronal processing and communication. By utilizing a recent improvement in voltage sensitive dye imaging technique that provided exceptional spatial and temporal resolution, we were able to resolve the region of spike initiation as well as follow spike propagation into axon collaterals for each action potential initiated on single trials. All fast action potentials, for both simple and complex spikes, whether occurring spontaneously or in response to a somatic current pulse or synaptic input, initiated in the axon initial segment. At discharge frequencies of less than approximately 250 Hz, spikes propagated faithfully through the axon and axon collaterals, in a saltatory manner. Propagation failures were only observed for very high frequencies or for the spikelets associated with complex spikes. These results demonstrate that the axon initial segment is a critical decision point in Purkinje cell processing and that the properties of axon branch points are adjusted to maintain faithful transmission. PMID:20484631

  14. A simulation of T-wave alternans vectocardiographic representation performed by changing the ventricular heart cells action potential duration.

    PubMed

    Janusek, D; Kania, M; Zaczek, R; Zavala-Fernandez, H; Maniewski, R

    2014-04-01

    The presence of T wave alternans (TWA) in the surface ECG signals has been recognized as a marker of electrical instability, and is hypothesized to be related to patients at increased risk for ventricular arrhythmias. In this paper we present a TWA simulation study. The TWA phenomenon was simulated by changing the duration of the ventricular heart cells action potential. The magnitude was calculated in the surface ECG with the use of the time domain method. The spatially concordant TWA, where during one heart beat all ventricular cells display a short-duration action potential and during the next beat they exhibit a long-duration action potential, as well as the discordant TWA, where at least one region is out of phase, was simulated. The vectocardiographic representation was employed. The obtained results showed a high level of T-loop pattern and location disturbances connected to the discordant TWA simulation in contrast to the concordant one. This result may be explained by the spatial heterogeneity of the ventricular repolarization process, which could be higher for the discordant TWA than for the concordant TWA. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  15. Dynamin phosphorylation controls optimization of endocytosis for brief action potential bursts

    PubMed Central

    Armbruster, Moritz; Messa, Mirko; Ferguson, Shawn M; De Camilli, Pietro; Ryan, Timothy A

    2013-01-01

    Modulation of synaptic vesicle retrieval is considered to be potentially important in steady-state synaptic performance. Here we show that at physiological temperature endocytosis kinetics at hippocampal and cortical nerve terminals show a bi-phasic dependence on electrical activity. Endocytosis accelerates for the first 15–25 APs during bursts of action potential firing, after which it slows with increasing burst length creating an optimum stimulus for this kinetic parameter. We show that activity-dependent acceleration is only prominent at physiological temperature and that the mechanism of this modulation is based on the dephosphorylation of dynamin 1. Nerve terminals in which dynamin 1 and 3 have been replaced with dynamin 1 harboring dephospho- or phospho-mimetic mutations in the proline-rich domain eliminate the acceleration phase by either setting endocytosis at an accelerated state or a decelerated state, respectively. DOI: http://dx.doi.org/10.7554/eLife.00845.001 PMID:23908769

  16. Heterogeneous memory in restitution of action potential duration in pig ventricles.

    PubMed

    Jing, Linyuan; Chourasia, Sonam; Patwardhan, Abhijit

    2010-01-01

    Restitution of action potential duration and memory importantly affect electrical stability in ventricles. Studies have reported heterogeneous restitution among different regions of the ventricles. However, existence of heterogeneity in memory is not as well investigated. Transmembrane potentials were recorded in endocardial and epicardial tissues from both ventricles of farm pigs. Pacing protocols with sinusoidally changing diastolic intervals were used to reveal hysteresis in restitution, from which quantitative measures of memory were calculated. Larger measures of hysteresis were observed in the endocardium than the epicardium (P < .05): loop thickness (in milliseconds), 26.9 vs 16.2; overall tilt, 0.376 vs 0.249; and loop area (in square milliseconds), 7288 vs 4146. Except for overall tilt, no significant differences in these measures were observed between ventricles. Heterogeneity in memory exists in pig ventricles. Because regions with the steepest restitution may also have the largest memory, our results suggest that heterogeneity in memory should also be factored in when predicting electrical stability. Copyright 2010 Elsevier Inc. All rights reserved.

  17. Stereoscopic Configurations To Minimize Distortions

    NASA Technical Reports Server (NTRS)

    Diner, Daniel B.

    1991-01-01

    Proposed television system provides two stereoscopic displays. Two-camera, two-monitor system used in various camera configurations and with stereoscopic images on monitors magnified to various degrees. Designed to satisfy observer's need to perceive spatial relationships accurately throughout workspace or to perceive them at high resolution in small region of workspace. Potential applications include industrial, medical, and entertainment imaging and monitoring and control of telemanipulators, telerobots, and remotely piloted vehicles.

  18. Configurational Molecular Glue: One Optically Active Polymer Attracts Two Oppositely Configured Optically Active Polymers.

    PubMed

    Tsuji, Hideto; Noda, Soma; Kimura, Takayuki; Sobue, Tadashi; Arakawa, Yuki

    2017-03-24

    D-configured poly(D-lactic acid) (D-PLA) and poly(D-2-hydroxy-3-methylbutanoic acid) (D-P2H3MB) crystallized separately into their homo-crystallites when crystallized by precipitation or solvent evaporation, whereas incorporation of L-configured poly(L-2-hydroxybutanoic acid) (L-P2HB) in D-configured D-PLA and D-P2H3MB induced co-crystallization or ternary stereocomplex formation between D-configured D-PLA and D-P2H3MB and L-configured L-P2HB. However, incorporation of D-configured poly(D-2-hydroxybutanoic acid) (D-P2HB) in D-configured D-PLA and D-P2H3MB did not cause co-crystallization between D-configured D-PLA and D-P2H3MB and D-configured D-P2HB but separate crystallization of each polymer occurred. These findings strongly suggest that an optically active polymer (L-configured or D-configured polymer) like unsubstituted or substituted optically active poly(lactic acid)s can act as "a configurational or helical molecular glue" for two oppositely configured optically active polymers (two D-configured polymers or two L-configured polymers) to allow their co-crystallization. The increased degree of freedom in polymer combination is expected to assist to pave the way for designing polymeric composites having a wide variety of physical properties, biodegradation rate and behavior in the case of biodegradable polymers.

  19. Configurational Molecular Glue: One Optically Active Polymer Attracts Two Oppositely Configured Optically Active Polymers

    NASA Astrophysics Data System (ADS)

    Tsuji, Hideto; Noda, Soma; Kimura, Takayuki; Sobue, Tadashi; Arakawa, Yuki

    2017-03-01

    D-configured poly(D-lactic acid) (D-PLA) and poly(D-2-hydroxy-3-methylbutanoic acid) (D-P2H3MB) crystallized separately into their homo-crystallites when crystallized by precipitation or solvent evaporation, whereas incorporation of L-configured poly(L-2-hydroxybutanoic acid) (L-P2HB) in D-configured D-PLA and D-P2H3MB induced co-crystallization or ternary stereocomplex formation between D-configured D-PLA and D-P2H3MB and L-configured L-P2HB. However, incorporation of D-configured poly(D-2-hydroxybutanoic acid) (D-P2HB) in D-configured D-PLA and D-P2H3MB did not cause co-crystallization between D-configured D-PLA and D-P2H3MB and D-configured D-P2HB but separate crystallization of each polymer occurred. These findings strongly suggest that an optically active polymer (L-configured or D-configured polymer) like unsubstituted or substituted optically active poly(lactic acid)s can act as “a configurational or helical molecular glue” for two oppositely configured optically active polymers (two D-configured polymers or two L-configured polymers) to allow their co-crystallization. The increased degree of freedom in polymer combination is expected to assist to pave the way for designing polymeric composites having a wide variety of physical properties, biodegradation rate and behavior in the case of biodegradable polymers.

  20. Increased transient Na+ conductance and action potential output in layer 2/3 prefrontal cortex neurons of the fmr1-/y mouse.

    PubMed

    Routh, Brandy N; Rathour, Rahul K; Baumgardner, Michael E; Kalmbach, Brian E; Johnston, Daniel; Brager, Darrin H

    2017-07-01

    Layer 2/3 neurons of the prefrontal cortex display higher gain of somatic excitability, responding with a higher number of action potentials for a given stimulus, in fmr1 -/y mice. In fmr1 -/y L2/3 neurons, action potentials are taller, faster and narrower. Outside-out patch clamp recordings revealed that the maximum Na + conductance density is higher in fmr1 -/y L2/3 neurons. Measurements of three biophysically distinct K + currents revealed a depolarizing shift in the activation of a rapidly inactivating (A-type) K + conductance. Realistic neuronal simulations of the biophysical observations recapitulated the elevated action potential and repetitive firing phenotype. Fragile X syndrome is the most common form of inherited mental impairment and autism. The prefrontal cortex is responsible for higher order cognitive processing, and prefrontal dysfunction is believed to underlie many of the cognitive and behavioural phenotypes associated with fragile X syndrome. We recently demonstrated that somatic and dendritic excitability of layer (L) 5 pyramidal neurons in the prefrontal cortex of the fmr1 -/y mouse is significantly altered due to changes in several voltage-gated ion channels. In addition to L5 pyramidal neurons, L2/3 pyramidal neurons play an important role in prefrontal circuitry, integrating inputs from both lower brain regions and the contralateral cortex. Using whole-cell current clamp recording, we found that L2/3 pyramidal neurons in prefrontal cortex of fmr1 -/y mouse fired more action potentials for a given stimulus compared with wild-type neurons. In addition, action potentials in fmr1 -/y neurons were significantly larger, faster and narrower. Voltage clamp of outside-out patches from L2/3 neurons revealed that the transient Na + current was significantly larger in fmr1 -/y neurons. Furthermore, the activation curve of somatic A-type K + current was depolarized. Realistic conductance-based simulations revealed that these biophysical changes in Na

  1. Action potentials in primary osteoblasts and in the MG-63 osteoblast-like cell line.

    PubMed

    Pangalos, Maria; Bintig, Willem; Schlingmann, Barbara; Feyerabend, Frank; Witte, Frank; Begandt, Daniela; Heisterkamp, Alexander; Ngezahayo, Anaclet

    2011-06-01

    Whole-cell patch-clamp analysis revealed a resting membrane potential of -60 mV in primary osteoblasts and in the MG-63 osteoblast-like cells. Depolarization-induced action potentials were characterized by duration of 60 ms, a minimal peak-to-peak distance of 180 ms, a threshold value of -20 mV and a repolarization between the spikes to -45 mV. Expressed channels were characterized by application of voltage pulses between -150 mV and 90 mV in 10 mV steps, from a holding potential of -40 mV. Voltages below -60 mV induced an inward current. Depolarizing voltages above -30 mV evoked two currents: (a) a fast activated and inactivated inward current at voltages between -30 and 30 mV, and (b) a delayed-activated outward current that was induced by voltages above -30 mV. Electrophysiological and pharmacological parameters indicated that hyperpolarization activated strongly rectifying K(+) (K(ir)) channels, whereas depolarization activated tetrodotoxin sensitive voltage gated Na(+) (Na(v)) channels as well as delayed, slowly activated, non-inactivating, and tetraethylammonium sensitive voltage gated K(+) (K(v)) channels. In addition, RT-PCR showed expression of Na(v)1.3, Na(v)1.4, Na(v)1.5, Na(v)1.6, Na(v)1.7, and K(ir)2.1, K(ir)2.3, and K(ir)2.4 as well as K(v)2.1. We conclude that osteoblasts express channels that allow firing of action potentials.

  2. ION Configuration Editor

    NASA Technical Reports Server (NTRS)

    Borgen, Richard L.

    2013-01-01

    The configuration of ION (Inter - planetary Overlay Network) network nodes is a manual task that is complex, time-consuming, and error-prone. This program seeks to accelerate this job and produce reliable configurations. The ION Configuration Editor is a model-based smart editor based on Eclipse Modeling Framework technology. An ION network designer uses this Eclipse-based GUI to construct a data model of the complete target network and then generate configurations. The data model is captured in an XML file. Intrinsic editor features aid in achieving model correctness, such as field fill-in, type-checking, lists of valid values, and suitable default values. Additionally, an explicit "validation" feature executes custom rules to catch more subtle model errors. A "survey" feature provides a set of reports providing an overview of the entire network, enabling a quick assessment of the model s completeness and correctness. The "configuration" feature produces the main final result, a complete set of ION configuration files (eight distinct file types) for each ION node in the network.

  3. Real time estimation of generation, extinction and flow of muscle fibre action potentials in high density surface EMG.

    PubMed

    Mesin, Luca

    2015-02-01

    Developing a real time method to estimate generation, extinction and propagation of muscle fibre action potentials from bi-dimensional and high density surface electromyogram (EMG). A multi-frame generalization of an optical flow technique including a source term is considered. A model describing generation, extinction and propagation of action potentials is fit to epochs of surface EMG. The algorithm is tested on simulations of high density surface EMG (inter-electrode distance equal to 5mm) from finite length fibres generated using a multi-layer volume conductor model. The flow and source term estimated from interference EMG reflect the anatomy of the muscle, i.e. the direction of the fibres (2° of average estimation error) and the positions of innervation zone and tendons under the electrode grid (mean errors of about 1 and 2mm, respectively). The global conduction velocity of the action potentials from motor units under the detection system is also obtained from the estimated flow. The processing time is about 1 ms per channel for an epoch of EMG of duration 150 ms. A new real time image processing algorithm is proposed to investigate muscle anatomy and activity. Potential applications are proposed in prosthesis control, automatic detection of optimal channels for EMG index extraction and biofeedback. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. Disentangling representations of shape and action components in the tool network.

    PubMed

    Wang, Xiaoying; Zhuang, Tonghe; Shen, Jiasi; Bi, Yanchao

    2018-05-30

    Shape and how they should be used are two key components of our knowledge about tools. Viewing tools preferentially activated a frontoparietal and occipitotemporal network, with dorsal regions implicated in computation of tool-related actions and ventral areas in shape representation. As shape and manners of manipulation are highly correlated for daily tools, whether they are independently represented in different regions remains inconclusive. In the current study, we collected fMRI data when participants viewed blocks of pictures of four daily tools (i.e., paintbrush, corkscrew, screwdriver, razor) where shape and action (manner of manipulation for functional use) were orthogonally manipulated, to tease apart these two dimensions. Behavioral similarity judgments tapping on object shape and finer aspects of actions (i.e., manners of motion, magnitude of arm movement, configuration of hand) were also collected to further disentangle the representation of object shape and different action components. Information analysis and representational similarity analysis were conducted on regional neural activation patterns of the tool-preferring network. In both analyses, the bilateral lateral occipitotemporal cortex showed robust shape representations but could not effectively distinguish between tool-use actions. The frontal and precentral regions represented kinematic action components, whereas the left parietal region (in information analyses) exhibited coding of both shape and tool-use action. By teasing apart shape and action components, we found both dissociation and association of them within the tool network. Taken together, our study disentangles representations for object shape from finer tool-use action components in the tool network, revealing the potential dissociable roles different tool-preferring regions play in tool processing. Copyright © 2018 Elsevier Ltd. All rights reserved.

  5. Sustaining Action and Optimizing Entropy: Coupling Efficiency for Energy and the Sustainability of Global Ecosystems

    ERIC Educational Resources Information Center

    Rose, Michael T.; Crossan, Angus N.; Kennedy, Ivan R.

    2008-01-01

    Consideration of the property of action is proposed to provide a more meaningful definition of efficient energy use and sustainable production in ecosystems. Action has physical dimensions similar to angular momentum, its magnitude varying with mass, spatial configuration and relative motion. In this article, the relationship of action to…

  6. Determining potential 30/20 GHz domestic satellite system concepts and establishment of a suitable experimental configuration

    NASA Technical Reports Server (NTRS)

    Stevens, G. H.; Anzic, G.

    1979-01-01

    Issues and results in a NASA study of the potential concepts and markets for a multibeam 30/20 GHz domestic satellite system in the 1990s are presented. Issues considered include the reduction of signal attenuation due to rain, beam-beam interference isolation in the multibeam system, the method of access/modulation (FDMA, TDMA or hybrid) and the market for reduced reliability and wideband services. A hypothetical demonstration payload configuration which would attempt to resolve these issues is illustrated. The communications payload would employ a system of seven contiguous coverage spots in order to demonstrate a typical cell in a contiguous beam system having extensive frequency re-use, as in a direct-to-user system, and a single spot, typical of a trunking system, to determine signal isolation. The payload could be carried on several existing buses and is illustrated on an MMS bus.

  7. Compound muscle action potential duration in critical illness neuromyopathy.

    PubMed

    Kramer, Christopher L; Boon, Andrea J; Harper, C Michel; Goodman, Brent P

    2018-03-01

    We sought to determine the specificity of compound muscle action potential (CMAP) durations and amplitudes in a large critical illness neuromyopathy (CINM) cohort relative to controls with other neuromuscular conditions. Fifty-eight patients with CINM who had been seen over a 17-year period were retrospectively studied. Electrodiagnostic findings of the CINM cohort were compared with patients with axonal peripheral neuropathy and myopathy due to other causes. Mean CMAP durations were prolonged, and mean CMAP amplitudes were severely reduced both proximally and distally in all nerves studied in the CINM cohort relative to the control groups. The specificity of prolonged CMAP durations for CINM approached 100% if they were encountered in more than 1 nerve. Prolonged, low-amplitude CMAPs occur more frequently and with greater severity in CINM patients than in neuromuscular controls with myopathy and axonal neuropathy and are highly specific for the diagnosis of CINM. Muscle Nerve 57: 395-400, 2018. © 2017 Wiley Periodicals, Inc.

  8. RIM-BPs Mediate Tight Coupling of Action Potentials to Ca(2+)-Triggered Neurotransmitter Release.

    PubMed

    Acuna, Claudio; Liu, Xinran; Gonzalez, Aneysis; Südhof, Thomas C

    2015-09-23

    Ultrafast neurotransmitter release requires tight colocalization of voltage-gated Ca(2+) channels with primed, release-ready synaptic vesicles at the presynaptic active zone. RIM-binding proteins (RIM-BPs) are multidomain active zone proteins that bind to RIMs and to Ca(2+) channels. In Drosophila, deletion of RIM-BPs dramatically reduces neurotransmitter release, but little is known about RIM-BP function in mammalian synapses. Here, we generated double conditional knockout mice for RIM-BP1 and RIM-BP2, and analyzed RIM-BP-deficient synapses in cultured hippocampal neurons and the calyx of Held. Surprisingly, we find that in murine synapses, RIM-BPs are not essential for neurotransmitter release as such, but are selectively required for high-fidelity coupling of action potential-induced Ca(2+) influx to Ca(2+)-stimulated synaptic vesicle exocytosis. Deletion of RIM-BPs decelerated action-potential-triggered neurotransmitter release and rendered it unreliable, thereby impairing the fidelity of synaptic transmission. Thus, RIM-BPs ensure optimal organization of the machinery for fast release in mammalian synapses without being a central component of the machinery itself. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Simulation study on compressive laminar optical tomography for cardiac action potential propagation

    PubMed Central

    Harada, Takumi; Tomii, Naoki; Manago, Shota; Kobayashi, Etsuko; Sakuma, Ichiro

    2017-01-01

    To measure the activity of tissue at the microscopic level, laminar optical tomography (LOT), which is a microscopic form of diffuse optical tomography, has been developed. However, obtaining sufficient recording speed to determine rapidly changing dynamic activity remains major challenges. For a high frame rate of the reconstructed data, we here propose a new LOT method using compressed sensing theory, called compressive laminar optical tomography (CLOT), in which novel digital micromirror device-based illumination and data reduction in a single reconstruction are applied. In the simulation experiments, the reconstructed volumetric images of the action potentials that were acquired from 5 measured images with random pattern featured a wave border at least to a depth of 2.5 mm. Consequently, it was shown that CLOT has potential for over 200 fps required for the cardiac electrophysiological phenomena. PMID:28736675

  10. Youth Participatory Action Research and Educational Transformation: The Potential of Intertextuality as a Methodological Tool

    ERIC Educational Resources Information Center

    Bertrand, Melanie

    2016-01-01

    In this article, Melanie Bertrand explores the potential of using the concept of intertextuality--which captures the way snippets of written or spoken text from one source become incorporated into other sources--in the study and practice of youth participatory action research (YPAR). Though this collective and youth-centered form of research…

  11. Velocity selection for ultracold atoms using mazer action in a bimodal cavity

    NASA Astrophysics Data System (ADS)

    Irshad, Afshan; Qamar, Sajid; Qamar, Shahid

    2010-01-01

    In this paper, we discuss the velocity selection of ultracold three-level atoms in Λ configuration using a mazer. Our model is the same as discussed by Arun et al. [R. Arun, G.S. Agarwal, M.O. Scully, H. Walther, Phys. Rev. A 62 (2000) 023809] for mazer action in a bimodal cavity. We show that the initial Maxwellian velocity distribution of ultracold atoms can be narrowed due to the presence of resonances in the transmission through dressed-state potential. When the atoms are initially prepared in one of the two lower atomic states then significantly better velocity selectivity is obtained due to the presence of dark states.

  12. Weakly Isolated horizons: first order actions and gauge symmetries

    NASA Astrophysics Data System (ADS)

    Corichi, Alejandro; Reyes, Juan D.; Vukašinac, Tatjana

    2017-04-01

    The notion of Isolated Horizons has played an important role in gravitational physics, being useful from the characterization of the endpoint of black hole mergers to (quantum) black hole entropy. With an eye towards a canonical formulation we consider general relativity in terms of connection and vierbein variables and their corresponding first order actions. We focus on two main issues: (i) The role of the internal gauge freedom that exists, in the consistent formulations of the action principle, and (ii) the role that a 3  +  1 canonical decomposition has in the allowed internal gauge freedom. More concretely, we clarify in detail how the requirement of having well posed variational principles compatible with general weakly isolated horizons (WIHs) as internal boundaries does lead to a partial gauge fixing in the first order descriptions used previously in the literature. We consider the standard Hilbert-Palatini action together with the Holst extension (needed for a consistent 3  +  1 decomposition), with and without boundary terms at the horizon. We show in detail that, for the complete configuration space—with no gauge fixing—, while the Palatini action is differentiable without additional surface terms at the inner WIH boundary, the more general Holst action is not. The introduction of a surface term at the horizon—that renders the action for asymptotically flat configurations differentiable—does make the Holst action differentiable, but only if one restricts the configuration space and partially reduces the internal Lorentz gauge. For the second issue at hand, we show that upon performing a 3  +  1 decomposition and imposing the time gauge, there is a further gauge reduction of the Hamiltonian theory in terms of Ashtekar-Barbero variables to a U(1)-gauge theory on the horizon. We also extend our analysis to the more restricted boundary conditions of (strongly) isolated horizons as inner boundary. We show that even when the

  13. The influence of action observation on action execution: Dissociating the contribution of action on perception, perception on action, and resolving conflict.

    PubMed

    Deschrijver, Eliane; Wiersema, Jan R; Brass, Marcel

    2017-04-01

    For more than 15 years, motor interference paradigms have been used to investigate the influence of action observation on action execution. Most research on so-called automatic imitation has focused on variables that play a modulating role or investigated potential confounding factors. Interestingly, furthermore, a number of functional magnetic resonance imaging (fMRI) studies have tried to shed light on the functional mechanisms and neural correlates involved in imitation inhibition. However, these fMRI studies, presumably due to poor temporal resolution, have primarily focused on high-level processes and have neglected the potential role of low-level motor and perceptual processes. In the current EEG study, we therefore aimed to disentangle the influence of low-level perceptual and motoric mechanisms from high-level cognitive mechanisms. We focused on potential congruency differences in the visual N190 - a component related to the processing of biological motion, the Readiness Potential - a component related to motor preparation, and the high-level P3 component. Interestingly, we detected congruency effects in each of these components, suggesting that the interference effect in an automatic imitation paradigm is not only related to high-level processes such as self-other distinction but also to more low-level influences of perception on action and action on perception. Moreover, we documented relationships of the neural effects with (autistic) behavior.

  14. PAN AIR: A computer program for predicting subsonic or supersonic linear potential flows about arbitrary configurations using a higher order panel method. Volume 1: Theory document (version 1.1)

    NASA Technical Reports Server (NTRS)

    Magnus, A. E.; Epton, M. A.

    1981-01-01

    Panel aerodynamics (PAN AIR) is a system of computer programs designed to analyze subsonic and supersonic inviscid flows about arbitrary configurations. A panel method is a program which solves a linear partial differential equation by approximating the configuration surface by a set of panels. An overview of the theory of potential flow in general and PAN AIR in particular is given along with detailed mathematical formulations. Fluid dynamics, the Navier-Stokes equation, and the theory of panel methods were also discussed.

  15. Auditory thresholds in the American cockroach (Orthoptera: Blattidae): estimates using single-unit and compound-action potential recordings.

    PubMed

    Decker, T N; Jones, T A; Gold, R E

    1989-06-01

    Recent commercial suggestions that insect populations can be controlled through the use of ultrasound raises the question of whether or not certain insects have receptors that are sensitive to high-frequency sound. Single neural unit discharges and compound-action potentials were recorded from the ventral nerve cord in the American cockroach, Periplaneta americana L., to constant rise time tone pulses from 100 to 40,000 hertz (Hz). Unit responses and compound-action potentials show that the cockroach is insensitive to sound above approximately 3,000 Hz. Data relating latency of the response to intensity of the stimulus suggest that the cockroach cercal system operates on the principle of energy envelope detection. Decreases in latency likely occur primarily as a result of increases in the rate of membrane depolarization in cercal dendrites.

  16. Actions and mechanisms of action of novel analogues of sotalol on guinea-pig and rabbit ventricular cells.

    PubMed Central

    Connors, S. P.; Gill, E. W.; Terrar, D. A.

    1992-01-01

    1. The actions and mechanisms of action of novel analogues of sotalol which prolong cardiac action potentials were investigated in guinea-pig and rabbit isolated ventricular cells. 2. In guinea-pig and rabbit cells the compounds significantly prolonged action potential duration at 20% and 90% repolarization levels without affecting resting membrane potential. In guinea-pig but not rabbit cells there was an increase in action potential amplitude and in rabbit cells there was no change in the shape or position of the 'notch' in the action potential. 3. Possible mechanisms of action were studied in more detail in the case of compound II (1-(4-methanesulphonamidophenoxy)-3-(N-methyl 3,4 dichlorophenylethylamino)-2-propanol). Prolongation of action potential duration continued to occur in the presence of nisoldipine, and calcium currents recorded under voltage-clamp conditions were not reduced by compound II (1 microM). Action potential prolongation by compound II was also unaffected in the presence of 10 microM tetrodotoxin. 4. Compound II (1 microM) did not influence IK1 assessed from the current during ramp changes in membrane potential (20 mV s-1) over the range -90 to -10 mV. 5. Compound II (1 microM) blocked time-dependent delayed rectifier potassium current (IK) activated by step depolarizations and recorded as an outward tail following repolarization. When a submaximal concentration (50 nM) was applied there was no change in the apparent reversal potential of IK.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1393293

  17. Stealth configurations in vector-tensor theories of gravity

    NASA Astrophysics Data System (ADS)

    Chagoya, Javier; Tasinato, Gianmassimo

    2018-01-01

    Studying the physics of compact objects in modified theories of gravity is important for understanding how future observations can test alternatives to General Relativity. We consider a subset of vector-tensor Galileon theories of gravity characterized by new symmetries, which can prevent the propagation of the vector longitudinal polarization, even in absence of Abelian gauge invariance. We investigate new spherically symmetric and slowly rotating solutions for these systems, including an arbitrary matter Lagrangian. We show that, under certain conditions, there always exist stealth configurations whose geometry coincides with solutions of Einstein gravity coupled with the additional matter. Such solutions have a non-trivial profile for the vector field, characterized by independent integration constants, which extends to asymptotic infinity. We interpret our findings in terms of the symmetries and features of the original vector-tensor action, and on the number of degrees of freedom that it propagates. These results are important to eventually describe gravitationally bound configurations in modified theories of gravity, such as black holes and neutron stars, including realistic matter fields forming or surrounding the object.

  18. The effect of recording site on extracted features of motor unit action potential.

    PubMed

    Artuğ, N Tuğrul; Goker, Imran; Bolat, Bülent; Osman, Onur; Kocasoy Orhan, Elif; Baslo, M Baris

    2016-06-01

    Motor unit action potential (MUAP), which consists of individual muscle fiber action potentials (MFAPs), represents the electrical activity of the motor unit. The values of the MUAP features are changed by denervation and reinnervation in neurogenic involvement as well as muscle fiber loss with increased diameter variability in myopathic diseases. The present study is designed to investigate how increased muscle fiber diameter variability affects MUAP parameters in simulated motor units. In order to detect this variation, simulated MUAPs were calculated both at the innervation zone where the MFAPs are more synchronized, and near the tendon, where they show increased temporal dispersion. Reinnervation in neurogenic state increases MUAP amplitude for the recordings at both the innervation zone and near the tendon. However, MUAP duration and the number of peaks significantly increased in a case of myopathy for recordings near the tendon. Furthermore, of the new features, "number of peaks×spike duration" was found as the strongest indicator of MFAP dispersion in myopathy. MUAPs were also recorded from healthy participants in order to investigate the biological counterpart of the simulation data. MUAPs which were recorded near to tendon revealed significantly prolonged duration and decreased amplitude. Although the number of peaks was increased by moving the needle near to tendon, this was not significant. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  19. Control of clustered action potential firing in a mathematical model of entorhinal cortex stellate cells.

    PubMed

    Tait, Luke; Wedgwood, Kyle; Tsaneva-Atanasova, Krasimira; Brown, Jon T; Goodfellow, Marc

    2018-07-14

    The entorhinal cortex is a crucial component of our memory and spatial navigation systems and is one of the first areas to be affected in dementias featuring tau pathology, such as Alzheimer's disease and frontotemporal dementia. Electrophysiological recordings from principle cells of medial entorhinal cortex (layer II stellate cells, mEC-SCs) demonstrate a number of key identifying properties including subthreshold oscillations in the theta (4-12 Hz) range and clustered action potential firing. These single cell properties are correlated with network activity such as grid firing and coupling between theta and gamma rhythms, suggesting they are important for spatial memory. As such, experimental models of dementia have revealed disruption of organised dorsoventral gradients in clustered action potential firing. To better understand the mechanisms underpinning these different dynamics, we study a conductance based model of mEC-SCs. We demonstrate that the model, driven by extrinsic noise, can capture quantitative differences in clustered action potential firing patterns recorded from experimental models of tau pathology and healthy animals. The differential equation formulation of our model allows us to perform numerical bifurcation analyses in order to uncover the dynamic mechanisms underlying these patterns. We show that clustered dynamics can be understood as subcritical Hopf/homoclinic bursting in a fast-slow system where the slow sub-system is governed by activation of the persistent sodium current and inactivation of the slow A-type potassium current. In the full system, we demonstrate that clustered firing arises via flip bifurcations as conductance parameters are varied. Our model analyses confirm the experimentally suggested hypothesis that the breakdown of clustered dynamics in disease occurs via increases in AHP conductance. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

  20. Microelectrode array measurement of potassium ion channel remodeling on the field action potential duration in rapid atrial pacing rabbits model.

    PubMed

    Sun, Juan; Yan, Huang; Wugeti, Najina; Guo, Yujun; Zhang, Ling; Ma, Mei; Guo, Xingui; Jiao, Changan; Xu, Wenli; Li, Tianqi

    2015-01-01

    Atrial fibrillation (AF) arises from abnormalities in atrial structure and electrical activity. Microelectrode arrays (MEA) is a real-time, nondestructive measurement of the resting and action potential signal, from myocardial cells, to the peripheral circuit of electrophysiological activity. This study examined the field action potential duration (fAPD) of the right atrial appendage (RAA) by MEA in rapid atrial pacing (RAP) in the right atrium of rabbits. In addition, this study also investigated the effect of potassium ion channel blockers on fAPD. 40 New Zealand white rabbits of either sex were randomly divided into 3 groups: 1) the control, 2) potassium ion channel blocker (TEA, 4-Ap and BaCl2), and 3) amiodarone groups. The hearts were quickly removed and right atrial appendage sectioned (slice thickness 500 μm). Each slice was perfused with Tyrode's solution and continuously stimulated for 30 minutes. Sections from the control group were superfused with Tyrode's solution for 10 minutes, while the blocker groups and amiodarone were both treated with their respective compounds for 10 minutes each. The fAPD of RAA and action field action potential morphology were measured using MEA. In non-pace (control) groups, fAPD was 188.33 ± 18.29 ms after Tyrode's solution superfusion, and 173.91 ± 6.83 ms after RAP. In pace/potassium ion channel groups, TEA and BaCl2 superfusion prolonged atrial field action potential (fAPD) (control vs blocker: 176.67 ± 8.66 ms vs 196.11 ± 10.76 ms, 182.22 ± 12.87 ms vs 191.11 ± 13.09 ms with TEA and BaCl2 superfusion, respectively, P < 0.05). 4-AP superfusion significantly prolonged FAPD. In pace/amiodarone groups, 4-Ap superfusion extended fAPD. MEA was a sensitive and stable reporter for the measurement of the tissue action potential in animal heart slices. After superfusing potassium ion channel blockers, fAPD was prolonged. These results suggest that Ito, IKur and IK1 remodel and mediate RAP-induced atrial electrical

  1. Are nonsymmetric balanced configurations of four equal masses virtual or real?

    NASA Astrophysics Data System (ADS)

    Chenciner, Alain

    2017-11-01

    Balanced configurations of N point masses are the configurations which, in a Euclidean space of high enough dimension, i. e., up to 2( N - 1), admit a relative equilibrium motion under the Newtonian (or similar) attraction. Central configurations are balanced and it has been proved by Alain Albouy that central configurations of four equal masses necessarily possess a symmetry axis, from which followed a proof that the number of such configurations up to similarity is finite and explicitly describable. It is known that balanced configurations of three equal masses are exactly the isosceles triangles, but it is not known whether balanced configurations of four equal masses must have some symmetry. As balanced configurations come in families, it makes sense to look for possible branches of nonsymmetric balanced configurations bifurcating from the subset of symmetric ones. In the simpler case of a logarithmic potential, the subset of symmetric balanced configurations of four equal masses is easy to describe as well as the bifurcation locus, but there is a grain of salt: expressed in terms of the squared mutual distances, this locus lies almost completely outside the set of true configurations (i. e., generalizations of triangular inequalities are not satisfied) and hence could lead most of the time only to the bifurcation of a branch of virtual nonsymmetric balanced configurations. Nevertheless, a tiny piece of the bifurcation locus lies within the subset of real balanced configurations symmetric with respect to a line and hence has a chance to lead to the bifurcation of real nonsymmetric balanced configurations. This raises the question of the title, a question which, thanks to the explicit description given here, should be solvable by computer experts even in the Newtonian case. Another interesting question is about the possibility for a bifurcating branch of virtual nonsymmetric balanced configurations to come back to the domain of true configurations.

  2. My action lasts longer: Potential link between subjective time and agency during voluntary action.

    PubMed

    Imaizumi, Shu; Asai, Tomohisa

    2017-05-01

    Time perception distorts across different phases of bodily movement. During motor execution, sensory feedback matching an internal sensorimotor prediction is perceived to last longer. The sensorimotor prediction also underlies sense of agency. We investigated association between subjective time and agency during voluntary action. Participants performed hand action while watching a video feedback of their hand with various delays to manipulate agency. The perceived duration and agency over the video feedback were judged. Minimal delay of the video feedback resulted in longer perceived duration than the actual duration and stronger agency, while substantial feedback delay resulted in shorter perceived duration and weaker agency. These fluctuations of perceived duration and agency were nullified by the feedback of other's hand instead of their own, but not by inverted feedback from a third-person perspective. Subjective time during action might be associated with agency stemming from sensorimotor prediction, and self-other distinction based on bodily appearance. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. 'Long-Cell Action' Corrosion: A Basic Mechanism Hidden Behind Components Degradation Issues in Nuclear Power Plants

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Genn Saji

    2006-07-01

    hazardous because of its localized nature compared with the local cell action corrosion. There exist various mechanisms (electrochemical cell configurations) that induce such potential differences, including: ionic concentration, aeration, temperature, flow velocity, radiation and corrosion potentials. In this paper, the author will discuss these potential differences and their relevance to the un-resolved corrosion issues in nuclear power plants. Due to the importance of this potential mechanism the author is calling for further verification experiments as a joint international project. (author)« less

  4. Computer-Drawn Field Lines and Potential Surfaces for a Wide Range of Field Configurations

    ERIC Educational Resources Information Center

    Brandt, Siegmund; Schneider, Hermann

    1976-01-01

    Describes a computer program that computes field lines and equipotential surfaces for a wide range of field configurations. Presents the mathematical technique and details of the program, the input data, and different modes of graphical representation. (MLH)

  5. Variability of acute extracellular action potential measurements with multisite silicon probes

    PubMed Central

    Scott, Kimberly M.; Du, Jiangang; Lester, Henry A.; Masmanidis, Sotiris C.

    2012-01-01

    Device miniaturization technologies have led to significant advances in sensors for extracellular measurements of electrical activity in the brain. Multisite, silicon-based probes containing implantable electrode arrays afford greater coverage of neuronal activity than single electrodes and therefore potentially offer a more complete view of how neuronal ensembles encode information. However, scaling up the number of sites is not sufficient to ensure capture of multiple neurons, as action potential signals from extracellular electrodes may vary due to numerous factors. In order to understand the large-scale recording capabilities and potential limitations of multisite probes, it is important to quantify this variability, and to determine whether certain key device parameters influence the recordings. Here we investigate the effect of four parameters, namely, electrode surface, width of the structural support shafts, shaft number, and position of the recording site relative to the shaft tip. This study employs acutely implanted silicon probes containing up to 64 recording sites, whose performance is evaluated by the metrics of noise, spike amplitude, and spike detection probability. On average, we find no significant effect of device geometry on spike amplitude and detection probability but we find significant differences among individual experiments, with the likelihood of detecting spikes varying by a factor of approximately three across trials. PMID:22971352

  6. Computational Modeling Reveals Key Contributions of KCNQ and hERG Currents to the Malleability of Uterine Action Potentials Underpinning Labor

    PubMed Central

    Tong, Wing-Chiu; Tribe, Rachel M.; Smith, Roger; Taggart, Michael J.

    2014-01-01

    The electrical excitability of uterine smooth muscle cells is a key determinant of the contraction of the organ during labor and is manifested by spontaneous, periodic action potentials (APs). Near the end of term, APs vary in shape and size reflecting an ability to change the frequency, duration and amplitude of uterine contractions. A recent mathematical model quantified several ionic features of the electrical excitability in uterine smooth muscle cells. It replicated many of the experimentally recorded uterine AP configurations but its limitations were evident when trying to simulate the long-duration bursting APs characteristic of labor. A computational parameter search suggested that delayed rectifying K+ currents could be a key model component requiring improvement to produce the longer-lasting bursting APs. Of the delayed rectifying K+ currents family it is of interest that KCNQ and hERG channels have been reported to be gestationally regulated in the uterus. These currents exhibit features similar to the broadly defined uterine I K1 of the original mathematical model. We thus formulated new quantitative descriptions for several I KCNQ and I hERG. Incorporation of these currents into the uterine cell model enabled simulations of the long-lasting bursting APs. Moreover, we used this modified model to simulate the effects of different contributions of I KCNQ and I hERG on AP form. Our findings suggest that the alterations in expression of hERG and KCNQ channels can potentially provide a mechanism for fine tuning of AP forms that lends a malleability for changing between plateau-like and long-lasting bursting-type APs as uterine cells prepare for parturition. PMID:25474527

  7. Regulation of gap junction conductance by calcineurin through Cx43 phosphorylation: implications for action potential conduction.

    PubMed

    Jabr, Rita I; Hatch, Fiona S; Salvage, Samantha C; Orlowski, Alejandro; Lampe, Paul D; Fry, Christopher H

    2016-11-01

    Cardiac arrhythmias are associated with raised intracellular [Ca 2+ ] and slowed action potential conduction caused by reduced gap junction (GJ) electrical conductance (Gj). Ventricular GJs are composed of connexin proteins (Cx43), with Gj determined by Cx43 phosphorylation status. Connexin phosphorylation is an interplay between protein kinases and phosphatases but the precise pathways are unknown. We aimed to identify key Ca 2+ -dependent phosphorylation sites on Cx43 that regulate cardiac gap junction conductance and action potential conduction velocity. We investigated the role of the Ca 2+ -dependent phosphatase, calcineurin. Intracellular [Ca 2+ ] was raised in guinea-pig myocardium by a low-Na solution or increased stimulation. Conduction velocity and Gj were measured in multicellular strips. Phosphorylation of Cx43 serine residues (S365 and S368) and of the intermediary regulator I1 at threonine35 was measured by Western blot. Measurements were made in the presence and absence of inhibitors to calcineurin, I1 or protein phosphatase-1 and phosphatase-2.Raised [Ca 2 + ] i decreased Gj, reduced Cx43 phosphorylation at S365 and increased it at S368; these changes were reversed by calcineurin inhibitors. Cx43-S368 phosphorylation was reversed by the protein kinase C inhibitor chelerythrine. Raised [Ca 2+ ] i also decreased I1 phosphorylation, also prevented by calcineurin inhibitors, to increase activity of the Ca 2+ -independent phosphatase, PPI. The PP1 inhibitor, tautomycin, prevented Cx43-365 dephosphorylation, Cx43-S368 phosphorylation and Gj reduction in raised [Ca 2+ ] i . PP2A had no role. Conduction velocity was reduced by raised [Ca 2+ ] i and reversed by calcineurin inhibitors. Reduced action potential conduction and Gj in raised [Ca 2+ ] are regulated by calcineurin-dependent Cx43-S365 phosphorylation, leading to Cx43-S368 dephosphorylation. The calcineurin action is indirect, via I1 dephosphorylation and subsequent activation of PP1.

  8. Crayfish neuromuscular facilitation activated by constant presynaptic action potentials and depolarizing pulses

    PubMed Central

    Zucker, Robert S.

    1974-01-01

    1. Experiments were conducted to test the hypothesis that facilitation of transmitter release in response to repetitive stimulation of the exciter motor axon to the crayfish claw opener muscle is due to an increase in the amplitude or duration of the action potential in presynaptic terminals. No consistent changes were found in the nerve terminal potential (n.t.p.) recorded extracellularly at synaptic sites on the surface of muscle fibres. 2. Apparent changes in n.t.p. are attributed to three causes. (i) Some recordings are shown to be contaminated by non-specific muscle responses which grow during facilitation. (ii) Some averaged n.t.p.s exhibit opposite changes in amplitude and duration which suggest a change in the synchrony of presynaptic nerve impulses at different frequencies. (iii) Some changes in n.t.p. are blocked by γ-methyl glutamate, an antagonist of the post-synaptic receptor, which suggests that these changes are caused by small muscle movements. 3. The only change in n.t.p. believed to represent an actual change in the intracellular signal is a reduction in n.t.p. amplitude to the second of two stimuli separated by a brief interval. 4. Tetra-ethyl ammonium ions increase synaptic transmission about 20% and prolong the n.t.p. about 15%. This result suggests that an increase in n.t.p. large enough to increase transmission by the several hundred per cent occurring during facilitation would be detected. 5. The nerve terminals are electrically excitable, and most synaptic sites have a diphasic or triphasic n.t.p., which suggests that the motor neurone terminals are actively invaded by nerve impulses. 6. When nerve impulses are blocked in tetrodotoxin, depolarization of nerve terminals increases the frequency of miniature excitatory junctional potentials (e.j.p.s), and a phasic e.j.p. can be evoked by large, brief depolarizing pulses. Responses to repetitive or paired depolarizations of constant amplitude and duration exhibit a facilitation similar to that

  9. Crayfish neuromuscular facilitation activated by constant presynaptic action potentials and depolarizing pulses.

    PubMed

    Zucker, R S

    1974-08-01

    1. Experiments were conducted to test the hypothesis that facilitation of transmitter release in response to repetitive stimulation of the exciter motor axon to the crayfish claw opener muscle is due to an increase in the amplitude or duration of the action potential in presynaptic terminals. No consistent changes were found in the nerve terminal potential (n.t.p.) recorded extracellularly at synaptic sites on the surface of muscle fibres.2. Apparent changes in n.t.p. are attributed to three causes.(i) Some recordings are shown to be contaminated by non-specific muscle responses which grow during facilitation.(ii) Some averaged n.t.p.s exhibit opposite changes in amplitude and duration which suggest a change in the synchrony of presynaptic nerve impulses at different frequencies.(iii) Some changes in n.t.p. are blocked by gamma-methyl glutamate, an antagonist of the post-synaptic receptor, which suggests that these changes are caused by small muscle movements.3. The only change in n.t.p. believed to represent an actual change in the intracellular signal is a reduction in n.t.p. amplitude to the second of two stimuli separated by a brief interval.4. Tetra-ethyl ammonium ions increase synaptic transmission about 20% and prolong the n.t.p. about 15%. This result suggests that an increase in n.t.p. large enough to increase transmission by the several hundred per cent occurring during facilitation would be detected.5. The nerve terminals are electrically excitable, and most synaptic sites have a diphasic or triphasic n.t.p., which suggests that the motor neurone terminals are actively invaded by nerve impulses.6. When nerve impulses are blocked in tetrodotoxin, depolarization of nerve terminals increases the frequency of miniature excitatory junctional potentials (e.j.p.s), and a phasic e.j.p. can be evoked by large, brief depolarizing pulses. Responses to repetitive or paired depolarizations of constant amplitude and duration exhibit a facilitation similar to that of e

  10. Action of bradykinin potentiating factor (BPF) and dimercaprol (BAL) on the responses to bradykinin of isolated preparations of rat intestines.

    PubMed

    Camargo, A; Ferreira, S H

    1971-06-01

    BPF and BAL inhibited kininase activity of homogenates of rat intestine. However, BFP potentiated and BAL inhibited the contractions induced by bradykinin on rat isolated duodenum (low calcium solution) and terminal ileum (normal calcium solution). Neither BPF nor BAL affects the relaxation induced by bradykinin of rat duodenum bathed in normal Tyrode. These results suggest that two different types of pharmacological receptor are involved in the action of bradykinin on rat intestine, and that other factors besides the inhibition of agonist destruction participate in the mechanism of potentiation of kinin action by BPF.

  11. Action of bradykinin potentiating factor (BPF) and dimercaprol (BAL) on the responses to bradykinin of isolated preparations of rat intestines

    PubMed Central

    Camargo, A.; Ferreira, S. H.

    1971-01-01

    BPF and BAL inhibited kininase activity of homogenates of rat intestine. However, BFP potentiated and BAL inhibited the contractions induced by bradykinin on rat isolated duodenum (low calcium solution) and terminal ileum (normal calcium solution). Neither BPF nor BAL affects the relaxation induced by bradykinin of rat duodenum bathed in normal Tyrode. These results suggest that two different types of pharmacological receptor are involved in the action of bradykinin on rat intestine, and that other factors besides the inhibition of agonist destruction participate in the mechanism of potentiation of kinin action by BPF. PMID:5091164

  12. 78 FR 47014 - Configuration Management Plans for Digital Computer Software Used in Safety Systems of Nuclear...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-02

    ... Software Used in Safety Systems of Nuclear Power Plants AGENCY: Nuclear Regulatory Commission. ACTION... Computer Software Used in Safety Systems of Nuclear Power Plants.'' This RG endorses, with clarifications... Electrical and Electronic Engineers (IEEE) Standard 828-2005, ``IEEE Standard for Software Configuration...

  13. Configuration Management Policy

    EPA Pesticide Factsheets

    This Policy establishes an Agency-wide Configuration Management Program and to provide responsibilities, compliance requirements, and overall principles for Configuration and Change Management processes to support information technology management.

  14. High-resolution room-temperature sample scanning superconducting quantum interference device microscope configurable for geological and biomagnetic applications

    NASA Astrophysics Data System (ADS)

    Fong, L. E.; Holzer, J. R.; McBride, K. K.; Lima, E. A.; Baudenbacher, F.; Radparvar, M.

    2005-05-01

    We have developed a scanning superconducting quantum interference device (SQUID) microscope system with interchangeable sensor configurations for imaging magnetic fields of room-temperature (RT) samples with submillimeter resolution. The low-critical-temperature (Tc) niobium-based monolithic SQUID sensors are mounted on the tip of a sapphire and thermally anchored to the helium reservoir. A 25μm sapphire window separates the vacuum space from the RT sample. A positioning mechanism allows us to adjust the sample-to-sensor spacing from the top of the Dewar. We achieved a sensor-to-sample spacing of 100μm, which could be maintained for periods of up to four weeks. Different SQUID sensor designs are necessary to achieve the best combination of spatial resolution and field sensitivity for a given source configuration. For imaging thin sections of geological samples, we used a custom-designed monolithic low-Tc niobium bare SQUID sensor, with an effective diameter of 80μm, and achieved a field sensitivity of 1.5pT/Hz1/2 and a magnetic moment sensitivity of 5.4×10-18Am2/Hz1/2 at a sensor-to-sample spacing of 100μm in the white noise region for frequencies above 100Hz. Imaging action currents in cardiac tissue requires a higher field sensitivity, which can only be achieved by compromising spatial resolution. We developed a monolithic low-Tc niobium multiloop SQUID sensor, with sensor sizes ranging from 250μm to 1mm, and achieved sensitivities of 480-180fT /Hz1/2 in the white noise region for frequencies above 100Hz, respectively. For all sensor configurations, the spatial resolution was comparable to the effective diameter and limited by the sensor-to-sample spacing. Spatial registration allowed us to compare high-resolution images of magnetic fields associated with action currents and optical recordings of transmembrane potentials to study the bidomain nature of cardiac tissue or to match petrography to magnetic field maps in thin sections of geological samples.

  15. Dynamic positioning configuration and its first-order optimization

    NASA Astrophysics Data System (ADS)

    Xue, Shuqiang; Yang, Yuanxi; Dang, Yamin; Chen, Wu

    2014-02-01

    Traditional geodetic network optimization deals with static and discrete control points. The modern space geodetic network is, on the other hand, composed of moving control points in space (satellites) and on the Earth (ground stations). The network configuration composed of these facilities is essentially dynamic and continuous. Moreover, besides the position parameter which needs to be estimated, other geophysical information or signals can also be extracted from the continuous observations. The dynamic (continuous) configuration of the space network determines whether a particular frequency of signals can be identified by this system. In this paper, we employ the functional analysis and graph theory to study the dynamic configuration of space geodetic networks, and mainly focus on the optimal estimation of the position and clock-offset parameters. The principle of the D-optimization is introduced in the Hilbert space after the concept of the traditional discrete configuration is generalized from the finite space to the infinite space. It shows that the D-optimization developed in the discrete optimization is still valid in the dynamic configuration optimization, and this is attributed to the natural generalization of least squares from the Euclidean space to the Hilbert space. Then, we introduce the principle of D-optimality invariance under the combination operation and rotation operation, and propose some D-optimal simplex dynamic configurations: (1) (Semi) circular configuration in 2-dimensional space; (2) the D-optimal cone configuration and D-optimal helical configuration which is close to the GPS constellation in 3-dimensional space. The initial design of GPS constellation can be approximately treated as a combination of 24 D-optimal helixes by properly adjusting the ascending node of different satellites to realize a so-called Walker constellation. In the case of estimating the receiver clock-offset parameter, we show that the circular configuration, the

  16. Modulating DNA configuration by interfacial traction: an elastic rod model to characterize DNA folding and unfolding.

    PubMed

    Huang, Zaixing

    2011-01-01

    As a continuum model of DNA, a thin elastic rod subjected to interfacial interactions is used to investigate the equilibrium configuration of DNA in intracellular solution. The interfacial traction between the rod and the solution environment is derived in detail. Kirchhoff's theory of elastic rods is used to analyze the equilibrium configuration of a DNA segment under the action of the interfacial traction. The influences of the interfacial energy factor and bending stiffness on the toroidal spool formation of the DNA segment are discussed. The results show that the equilibrium configuration of DNA is mainly determined by competition between the interfacial energy and elastic strain energy of the DNA itself, and the interfacial traction is one of the forces that drives DNA folding and unfolding.

  17. Duration of the distal compound muscle action potential for diagnosis of chronic inflammatory demyelinating polyneuropathy: effects of low-cut filters.

    PubMed

    Isose, Sagiri; Misawa, Sonoko; Sonoo, Masahiro; Shimuzu, Toshio; Oishi, Chizuko; Shibuya, Kazumoto; Nasu, Saiko; Sekiguchi, Yukari; Mitsuma, Satsuki; Beppu, Minako; Omori, Shigeki; Komori, Tetsuo; Kokubun, Norito; Inaba, Akira; Hirashima, Fumiko; Kuwabara, Satoshi

    2014-10-01

    In current electrodiagnostic criteria for chronic inflammatory demyelinating polyneuropathy, the cutoff values of distal compound muscle action potential (DCMAP) duration are defined using electromyogram low-cut filter setting of 20 Hz. We aimed to assess effects of low-cut filter on DCMAP duration (10 vs. 20 Hz). We prospectively measured DCMAP duration in 130 normal controls and 42 patients, fulfilling diagnostic criteria for typical chronic inflammatory demyelinating polyneuropathy by European Federation of Neurological Societies/Peripheral Nerve Society. Distal compound muscle action potential duration was significantly shortened with 20-Hz than 10-Hz filtering. When the cutoff values were defined as the upper limit of normal (ULN, mean + 2.5SD), the sensitivity/specificity was 67%/95% in 10-Hz recordings, and 69%/95% in 20-Hz recordings. This diagnostic accuracy was similar to that defined by receiver operating characteristic analyses. Distal compound muscle action potential duration significantly affected by the low-cut electromyogram filter setting, but with at least 10 and 20 Hz, the diagnostic accuracy is similar.

  18. Single K ATP channel opening in response to action potential firing in mouse dentate granule neurons.

    PubMed

    Tanner, Geoffrey R; Lutas, Andrew; Martínez-François, Juan Ramón; Yellen, Gary

    2011-06-08

    ATP-sensitive potassium channels (K(ATP) channels) are important sensors of cellular metabolic state that link metabolism and excitability in neuroendocrine cells, but their role in nonglucosensing central neurons is less well understood. To examine a possible role for K(ATP) channels in modulating excitability in hippocampal circuits, we recorded the activity of single K(ATP) channels in cell-attached patches of granule cells in the mouse dentate gyrus during bursts of action potentials generated by antidromic stimulation of the mossy fibers. Ensemble averages of the open probability (p(open)) of single K(ATP) channels over repeated trials of stimulated spike activity showed a transient increase in p(open) in response to action potential firing. Channel currents were identified as K(ATP) channels through blockade with glibenclamide and by comparison with recordings from Kir6.2 knock-out mice. The transient elevation in K(ATP) p(open) may arise from submembrane ATP depletion by the Na(+)-K(+) ATPase, as the pump blocker strophanthidin reduced the magnitude of the elevation. Both the steady-state and stimulus-elevated p(open) of the recorded channels were higher in the presence of the ketone body R-β-hydroxybutyrate, consistent with earlier findings that ketone bodies can affect K(ATP) activity. Using perforated-patch recording, we also found that K(ATP) channels contribute to the slow afterhyperpolarization following an evoked burst of action potentials. We propose that activity-dependent opening of K(ATP) channels may help granule cells act as a seizure gate in the hippocampus and that ketone-body-mediated augmentation of the activity-dependent opening could in part explain the effect of the ketogenic diet in reducing epileptic seizures.

  19. Configurational entropy as a lifetime predictor and pattern discriminator for oscillons

    NASA Astrophysics Data System (ADS)

    Gleiser, Marcelo; Stephens, Michelle; Sowinski, Damian

    2018-05-01

    Oscillons are long-lived, spherically symmetric, attractor scalar field configurations that emerge as certain field configurations evolve in time. It has been known for many years that there is a direct correlation between the initial configuration's shape and the resulting oscillon lifetime: a shape memory. In this paper, we use an information-entropic measure of spatial complexity known as differential configurational entropy (DCE) to obtain estimates of oscillon lifetimes in scalar field theories with symmetric and asymmetric double-well potentials. The time-dependent DCE is built from the Fourier transform of the two-point correlation function of the energy density of the scalar field configuration. We obtain a scaling law correlating oscillon lifetimes and measures obtained from its evolving DCE. For the symmetric double well, for example, we show that we can apply DCE to predict an oscillon's lifetime with an average accuracy of 6% or better. We also show that the DCE acts as a pattern discriminator, able to distinguish initial configurations that evolve into long-lived oscillons from other nonperturbative short-lived fluctuations.

  20. Configuration selection for a 450-passenger ultraefficient 2020 aircraft

    NASA Astrophysics Data System (ADS)

    Paulus, D.; Salmon, T.; Mohr, B.; Roessler, C.; Petersson, Ӧ.; Stroscher, F.; Baier, H.; Hornung, M.

    2013-12-01

    This paper describes the configuration selection process in the FP7 project ACFA (Active Control for Flexible Aircraft) 2020 in view of the Advisory Council for Aeronautics Research in Europe (ACARE) aims. The design process challenges and the comparison of a blended wing body (BWB) aircraft with a wide body carry-through wing box (CWB) configuration are described in detail. Furthermore, the interactions between the conceptual design and structural design using multidisciplinary design optimization (MDO) to rapidly generate and adapt structural models to design changes and provide early feedback of mass and center of gravity values for these nontraditional configurations are discussed. Comparison of the two concepts determined that the developed all-lifting BWB airframe has the potential for a significant reduced fuel consumption compared to the CWB.

  1. An ultra low-power CMOS automatic action potential detector.

    PubMed

    Gosselin, Benoit; Sawan, Mohamad

    2009-08-01

    We present a low-power complementary metal-oxide semiconductor (CMOS) analog integrated biopotential detector intended for neural recording in wireless multichannel implants. The proposed detector can achieve accurate automatic discrimination of action potential (APs) from the background activity by means of an energy-based preprocessor and a linear delay element. This strategy improves detected waveforms integrity and prompts for better performance in neural prostheses. The delay element is implemented with a low-power continuous-time filter using a ninth-order equiripple allpass transfer function. All circuit building blocks use subthreshold OTAs employing dedicated circuit techniques for achieving ultra low-power and high dynamic range. The proposed circuit function in the submicrowatt range as the implemented CMOS 0.18- microm chip dissipates 780 nW, and it features a size of 0.07 mm(2). So it is suitable for massive integration in a multichannel device with modest overhead. The fabricated detector succeeds to automatically detect APs from underlying background activity. Testbench validation results obtained with synthetic neural waveforms are presented.

  2. A four-component model of the action potential in mouse detrusor smooth muscle cell

    PubMed Central

    Brain, Keith L.; Young, John S.; Manchanda, Rohit

    2018-01-01

    Background and hypothesis Detrusor smooth muscle cells (DSMCs) of the urinary bladder are electrically connected to one another via gap junctions and form a three dimensional syncytium. DSMCs exhibit spontaneous electrical activity, including passive depolarizations and action potentials. The shapes of spontaneous action potentials (sAPs) observed from a single DSM cell can vary widely. The biophysical origins of this variability, and the precise components which contribute to the complex shapes observed are not known. To address these questions, the basic components which constitute the sAPs were investigated. We hypothesized that linear combinations of scaled versions of these basic components can produce sAP shapes observed in the syncytium. Methods and results The basic components were identified as spontaneous evoked junction potentials (sEJP), native AP (nAP), slow after hyperpolarization (sAHP) and very slow after hyperpolarization (vsAHP). The experimental recordings were grouped into two sets: a training data set and a testing data set. A training set was used to estimate the components, and a test set to evaluate the efficiency of the estimated components. We found that a linear combination of the identified components when appropriately amplified and time shifted replicated various AP shapes to a high degree of similarity, as quantified by the root mean square error (RMSE) measure. Conclusions We conclude that the four basic components—sEJP, nAP, sAHP, and vsAHP—identified and isolated in this work are necessary and sufficient to replicate all varieties of the sAPs recorded experimentally in DSMCs. This model has the potential to generate testable hypotheses that can help identify the physiological processes underlying various features of the sAPs. Further, this model also provides a means to classify the sAPs into various shape classes. PMID:29351282

  3. A four-component model of the action potential in mouse detrusor smooth muscle cell.

    PubMed

    Padmakumar, Mithun; Brain, Keith L; Young, John S; Manchanda, Rohit

    2018-01-01

    Detrusor smooth muscle cells (DSMCs) of the urinary bladder are electrically connected to one another via gap junctions and form a three dimensional syncytium. DSMCs exhibit spontaneous electrical activity, including passive depolarizations and action potentials. The shapes of spontaneous action potentials (sAPs) observed from a single DSM cell can vary widely. The biophysical origins of this variability, and the precise components which contribute to the complex shapes observed are not known. To address these questions, the basic components which constitute the sAPs were investigated. We hypothesized that linear combinations of scaled versions of these basic components can produce sAP shapes observed in the syncytium. The basic components were identified as spontaneous evoked junction potentials (sEJP), native AP (nAP), slow after hyperpolarization (sAHP) and very slow after hyperpolarization (vsAHP). The experimental recordings were grouped into two sets: a training data set and a testing data set. A training set was used to estimate the components, and a test set to evaluate the efficiency of the estimated components. We found that a linear combination of the identified components when appropriately amplified and time shifted replicated various AP shapes to a high degree of similarity, as quantified by the root mean square error (RMSE) measure. We conclude that the four basic components-sEJP, nAP, sAHP, and vsAHP-identified and isolated in this work are necessary and sufficient to replicate all varieties of the sAPs recorded experimentally in DSMCs. This model has the potential to generate testable hypotheses that can help identify the physiological processes underlying various features of the sAPs. Further, this model also provides a means to classify the sAPs into various shape classes.

  4. Ventricular filling slows epicardial conduction and increases action potential duration in an optical mapping study of the isolated rabbit heart.

    PubMed

    Sung, Derrick; Mills, Robert W; Schettler, Jan; Narayan, Sanjiv M; Omens, Jeffrey H; McCulloch, Andrew D

    2003-07-01

    Mechanical stimulation can induce electrophysiologic changes in cardiac myocytes, but how mechanoelectric feedback in the intact heart affects action potential propagation remains unclear. Changes in action potential propagation and repolarization with increased left ventricular end-diastolic pressure from 0 to 30 mmHg were investigated using optical mapping in isolated perfused rabbit hearts. With respect to 0 mmHg, epicardial strain at 30 mmHg in the anterior left ventricle averaged 0.040 +/- 0.004 in the muscle fiber direction and 0.032 +/- 0.006 in the cross-fiber direction. An increase in ventricular loading increased average epicardial activation time by 25%+/- 3% (P < 0.0001) and correspondingly decreased average apparent surface conduction velocity by 16%+/- 7% (P = 0.007). Ventricular loading did not significantly alter action potential duration at 20% repolarization (APD20) but did at 80% repolarization (APD80), from 179 +/- 7 msec to 207 +/- 5 msec (P < 0.0001). The dispersion of APD20 was decreased with loading from 19 +/- 2 msec to 13 +/- 2 msec (P = 0.024), whereas the dispersion of APD80 was not significantly changed. These electrophysiologic changes with ventricular loading were not affected by the nonspecific stretch-activated channel blocker streptomycin (200 microM) and were not attributable to changes in myocardial perfusion or the presence of an electromechanical decoupling agent (butanedione monoxime) during optical mapping. Acute loading of the left ventricle of the isolated rabbit heart decreased apparent epicardial conduction velocity and increased action potential duration by a load-dependent mechanism that may not involve stretch-activated channels.

  5. Ventricular filling slows epicardial conduction and increases action potential duration in an optical mapping study of the isolated rabbit heart

    NASA Technical Reports Server (NTRS)

    Sung, Derrick; Mills, Robert W.; Schettler, Jan; Narayan, Sanjiv M.; Omens, Jeffrey H.; McCulloch, Andrew D.; McCullough, A. D. (Principal Investigator)

    2003-01-01

    INTRODUCTION: Mechanical stimulation can induce electrophysiologic changes in cardiac myocytes, but how mechanoelectric feedback in the intact heart affects action potential propagation remains unclear. METHODS AND RESULTS: Changes in action potential propagation and repolarization with increased left ventricular end-diastolic pressure from 0 to 30 mmHg were investigated using optical mapping in isolated perfused rabbit hearts. With respect to 0 mmHg, epicardial strain at 30 mmHg in the anterior left ventricle averaged 0.040 +/- 0.004 in the muscle fiber direction and 0.032 +/- 0.006 in the cross-fiber direction. An increase in ventricular loading increased average epicardial activation time by 25%+/- 3% (P < 0.0001) and correspondingly decreased average apparent surface conduction velocity by 16%+/- 7% (P = 0.007). Ventricular loading did not significantly alter action potential duration at 20% repolarization (APD20) but did at 80% repolarization (APD80), from 179 +/- 7 msec to 207 +/- 5 msec (P < 0.0001). The dispersion of APD20 was decreased with loading from 19 +/- 2 msec to 13 +/- 2 msec (P = 0.024), whereas the dispersion of APD80 was not significantly changed. These electrophysiologic changes with ventricular loading were not affected by the nonspecific stretch-activated channel blocker streptomycin (200 microM) and were not attributable to changes in myocardial perfusion or the presence of an electromechanical decoupling agent (butanedione monoxime) during optical mapping. CONCLUSION: Acute loading of the left ventricle of the isolated rabbit heart decreased apparent epicardial conduction velocity and increased action potential duration by a load-dependent mechanism that may not involve stretch-activated channels.

  6. Sympathetic Nervous Regulation of Calcium and Action Potential Alternans in the Intact Heart.

    PubMed

    Winter, James; Bishop, Martin J; Wilder, Catherine D E; O'Shea, Christopher; Pavlovic, Davor; Shattock, Michael J

    2018-01-01

    Rationale: Arrhythmogenic cardiac alternans are thought to be an important determinant for the initiation of ventricular fibrillation. There is limited information on the effects of sympathetic nerve stimulation (SNS) on alternans in the intact heart and the conclusions of existing studies, focused on investigating electrical alternans, are conflicted. Meanwhile, several lines of evidence implicate instabilities in Ca handling, not electrical restitution, as the primary mechanism underpinning alternans. Despite this, there have been no studies on Ca alternans and SNS in the intact heart. The present study sought to address this, by application of voltage and Ca optical mapping for the simultaneous study of APD and Ca alternans in the intact guinea pig heart during direct SNS. Objective : To determine the effects of SNS on APD and Ca alternans in the intact guinea pig heart and to examine the mechanism(s) by which the effects of SNS are mediated. Methods and Results : Studies utilized simultaneous voltage and Ca optical mapping in isolated guinea pig hearts with intact innervation. Alternans were induced using a rapid dynamic pacing protocol. SNS was associated with rate-independent shortening of action potential duration (APD) and the suppression of APD and Ca alternans, as indicated by a shift in the alternans threshold to faster pacing rates. Qualitatively similar results were observed with exogenous noradrenaline perfusion. In contrast with previous reports, both SNS and noradrenaline acted to flatten the slope of the electrical restitution curve. Pharmacological block of the slow delayed rectifying potassium current (I Ks ), sufficient to abolish I Ks -mediated APD-adaptation, partially reversed the effects of SNS on pacing-induced alternans. Treatment with cyclopiazonic acid, an inhibitor of the sarco(endo)plasmic reticulum ATPase, had opposite effects to that of SNS, acting to increase susceptibility to alternans, and suggesting that accelerated Ca reuptake

  7. A mathematical model of action potential heterogeneity in adult rat left ventricular myocytes.

    PubMed Central

    Pandit, S V; Clark, R B; Giles, W R; Demir, S S

    2001-01-01

    Mathematical models were developed to reconstruct the action potentials (AP) recorded in epicardial and endocardial myocytes isolated from the adult rat left ventricle. The main goal was to obtain additional insight into the ionic mechanisms responsible for the transmural AP heterogeneity. The simulation results support the hypothesis that the smaller density and the slower reactivation kinetics of the Ca(2+)-independent transient outward K(+) current (I(t)) in the endocardial myocytes can account for the longer action potential duration (APD), and more prominent rate dependence in that cell type. The larger density of the Na(+) current (I(Na)) in the endocardial myocytes results in a faster upstroke (dV/dt(max)). This, in addition to the smaller magnitude of I(t), is responsible for the larger peak overshoot of the simulated endocardial AP. The prolonged APD in the endocardial cell also leads to an enhanced amplitude of the sustained K(+) current (I(ss)), and a larger influx of Ca(2+) ions via the L-type Ca(2+) current (I(CaL)). The latter results in an increased sarcoplasmic reticulum (SR) load, which is mainly responsible for the higher peak systolic value of the Ca(2+) transient [Ca(2+)](i), and the resultant increase in the Na(+)-Ca(2+) exchanger (I(NaCa)) activity, associated with the simulated endocardial AP. In combination, these calculations provide novel, quantitative insights into the repolarization process and its naturally occurring transmural variations in the rat left ventricle. PMID:11720973

  8. A configural dominant account of contextual cueing: Configural cues are stronger than colour cues.

    PubMed

    Kunar, Melina A; John, Rebecca; Sweetman, Hollie

    2014-01-01

    Previous work has shown that reaction times to find a target in displays that have been repeated are faster than those for displays that have never been seen before. This learning effect, termed "contextual cueing" (CC), has been shown using contexts such as the configuration of the distractors in the display and the background colour. However, it is not clear how these two contexts interact to facilitate search. We investigated this here by comparing the strengths of these two cues when they appeared together. In Experiment 1, participants searched for a target that was cued by both colour and distractor configural cues, compared with when the target was only predicted by configural information. The results showed that the addition of a colour cue did not increase contextual cueing. In Experiment 2, participants searched for a target that was cued by both colour and distractor configuration compared with when the target was only cued by colour. The results showed that adding a predictive configural cue led to a stronger CC benefit. Experiments 3 and 4 tested the disruptive effects of removing either a learned colour cue or a learned configural cue and whether there was cue competition when colour and configural cues were presented together. Removing the configural cue was more disruptive to CC than removing colour, and configural learning was shown to overshadow the learning of colour cues. The data support a configural dominant account of CC, where configural cues act as the stronger cue in comparison to colour when they are presented together.

  9. Advanced supersonic technology concept study: Hydrogen fueled configuration

    NASA Technical Reports Server (NTRS)

    Brewer, G. D.

    1974-01-01

    Conceptual designs of hydrogen fueled supersonic transport configurations for the 1990 time period were developed and compared with equivalent technology Jet A-1 fueled vehicles to determine the economic and performance potential of liquid hydrogen as an alternate fuel. Parametric evaluations of supersonic cruise vehicles with varying design and transport mission characteristics established the basis for selecting a preferred configuration which was then studied in greater detail. An assessment was made of the general viability of the selected concept including an evaluation of costs and environmental considerations, i.e., exhaust emissions and sonic boom characteristics. Technology development requirements and suggested implementation schedules are presented.

  10. Influence of the magnetic field configuration on the plasma flow in Hall thrusters

    NASA Astrophysics Data System (ADS)

    Andreussi, T.; Giannetti, V.; Leporini, A.; Saravia, M. M.; Andrenucci, M.

    2018-01-01

    In Hall propulsion, the thrust is provided by the acceleration of ions in a plasma generated in a cross-field configuration. Standard thruster configurations have annular channels with an almost radial magnetic field at the channel exit. A potential difference is imposed in the axial direction and the intensity of the magnetic field is calibrated in order to hinder the electron motion, while leaving the ions non-magnetised. Magnetic field lines can be assumed, as a first approximation, as lines of constant electron temperature and of thermalized potential. In typical thruster configurations, the discharge occurs inside a ceramic channel and, due to plasma-wall interactions, the electron temperature is typically low, less than few tens of eV. Hence, the magnetic field lines can be effectively used to tailor the distribution of the electrostatic potential. However, the erosion of the ceramic walls caused by the ion bombardment represents the main limiting factor of the thruster lifetime and new thruster configurations are currently under development. For these configurations, classical first order models of the plasma dynamics fail to grasp the influence of the magnetic topology on the plasma flow. In the present paper, a novel approach to investigate the correlation between magnetic field topology and thruster performance is presented. Due to the anisotropy induced by the magnetic field, the gradients of the plasma properties are assumed to be mainly in the direction orthogonal to the local magnetic field, thus enabling a quasi-one-dimensional description in magnetic coordinates. Theoretical and experimental investigations performed on a 5 kW class Hall thruster with different magnetic field configurations are then presented and discussed.

  11. Can optical recordings of membrane potential be used to screen for drug-induced action potential prolongation in single cardiac myocytes?

    PubMed

    Hardy, M E L; Lawrence, C L; Standen, N B; Rodrigo, G C

    2006-01-01

    Potential-sensitive dyes have primarily been used to optically record action potentials (APs) in whole heart tissue. Using these dyes to record drug-induced changes in AP morphology of isolated cardiac myocytes could provide an opportunity to develop medium throughout assays for the pharmaceutical industry. Ideally, this requires that the dye has a consistent and rapid response to membrane potential, is insensitive to movement, and does not itself affect AP morphology. We recorded the AP from isolated adult guinea-pig ventricular myocytes optically using di-8-ANEPPS in a single-excitation dual-emission ratiometric system, either separately in electrically field stimulated myocytes, or simultaneously with an electrical AP recorded with a patch electrode in the whole-cell bridge mode. The ratio of di-8-ANEPPS fluorescence signal was calibrated against membrane potential using a switch-clamp to voltage clamp the myocyte. Our data show that the ratio of the optical signals emitted at 560/620 nm is linearly related to voltage over the voltage range of an AP, producing a change in ratio of 7.5% per 100 mV, is unaffected by cell movement and is identical to the AP recorded simultaneously with a patch electrode. However, the APD90 recorded optically in myocytes loaded with di-8-ANEPPS was significantly longer than in unloaded myocytes recorded with a patch electrode (355.6+/-13.5 vs. 296.2+/-16.2 ms; p<0.01). Despite this effect, the apparent IC50 for cisapride, which prolongs the AP by blocking IKr, was not significantly different whether determined optically or with a patch electrode (91+/-46 vs. 81+/-20 nM). These data show that the optical AP recorded ratiometrically using di-8-ANEPPS from a single ventricular myocyte accurately follows the action potential morphology. This technique can be used to estimate the AP prolonging effects of a compound, although di-8-ANEPPS itself prolongs APD90. Optical dyes require less technical skills and are less invasive than

  12. Waveform Similarity Analysis: A Simple Template Comparing Approach for Detecting and Quantifying Noisy Evoked Compound Action Potentials.

    PubMed

    Potas, Jason Robert; de Castro, Newton Gonçalves; Maddess, Ted; de Souza, Marcio Nogueira

    2015-01-01

    Experimental electrophysiological assessment of evoked responses from regenerating nerves is challenging due to the typical complex response of events dispersed over various latencies and poor signal-to-noise ratio. Our objective was to automate the detection of compound action potential events and derive their latencies and magnitudes using a simple cross-correlation template comparison approach. For this, we developed an algorithm called Waveform Similarity Analysis. To test the algorithm, challenging signals were generated in vivo by stimulating sural and sciatic nerves, whilst recording evoked potentials at the sciatic nerve and tibialis anterior muscle, respectively, in animals recovering from sciatic nerve transection. Our template for the algorithm was generated based on responses evoked from the intact side. We also simulated noisy signals and examined the output of the Waveform Similarity Analysis algorithm with imperfect templates. Signals were detected and quantified using Waveform Similarity Analysis, which was compared to event detection, latency and magnitude measurements of the same signals performed by a trained observer, a process we called Trained Eye Analysis. The Waveform Similarity Analysis algorithm could successfully detect and quantify simple or complex responses from nerve and muscle compound action potentials of intact or regenerated nerves. Incorrectly specifying the template outperformed Trained Eye Analysis for predicting signal amplitude, but produced consistent latency errors for the simulated signals examined. Compared to the trained eye, Waveform Similarity Analysis is automatic, objective, does not rely on the observer to identify and/or measure peaks, and can detect small clustered events even when signal-to-noise ratio is poor. Waveform Similarity Analysis provides a simple, reliable and convenient approach to quantify latencies and magnitudes of complex waveforms and therefore serves as a useful tool for studying evoked compound

  13. Waveform Similarity Analysis: A Simple Template Comparing Approach for Detecting and Quantifying Noisy Evoked Compound Action Potentials

    PubMed Central

    Potas, Jason Robert; de Castro, Newton Gonçalves; Maddess, Ted; de Souza, Marcio Nogueira

    2015-01-01

    Experimental electrophysiological assessment of evoked responses from regenerating nerves is challenging due to the typical complex response of events dispersed over various latencies and poor signal-to-noise ratio. Our objective was to automate the detection of compound action potential events and derive their latencies and magnitudes using a simple cross-correlation template comparison approach. For this, we developed an algorithm called Waveform Similarity Analysis. To test the algorithm, challenging signals were generated in vivo by stimulating sural and sciatic nerves, whilst recording evoked potentials at the sciatic nerve and tibialis anterior muscle, respectively, in animals recovering from sciatic nerve transection. Our template for the algorithm was generated based on responses evoked from the intact side. We also simulated noisy signals and examined the output of the Waveform Similarity Analysis algorithm with imperfect templates. Signals were detected and quantified using Waveform Similarity Analysis, which was compared to event detection, latency and magnitude measurements of the same signals performed by a trained observer, a process we called Trained Eye Analysis. The Waveform Similarity Analysis algorithm could successfully detect and quantify simple or complex responses from nerve and muscle compound action potentials of intact or regenerated nerves. Incorrectly specifying the template outperformed Trained Eye Analysis for predicting signal amplitude, but produced consistent latency errors for the simulated signals examined. Compared to the trained eye, Waveform Similarity Analysis is automatic, objective, does not rely on the observer to identify and/or measure peaks, and can detect small clustered events even when signal-to-noise ratio is poor. Waveform Similarity Analysis provides a simple, reliable and convenient approach to quantify latencies and magnitudes of complex waveforms and therefore serves as a useful tool for studying evoked compound

  14. Simulator for neural networks and action potentials.

    PubMed

    Baxter, Douglas A; Byrne, John H

    2007-01-01

    A key challenge for neuroinformatics is to devise methods for representing, accessing, and integrating vast amounts of diverse and complex data. A useful approach to represent and integrate complex data sets is to develop mathematical models [Arbib (The Handbook of Brain Theory and Neural Networks, pp. 741-745, 2003); Arbib and Grethe (Computing the Brain: A Guide to Neuroinformatics, 2001); Ascoli (Computational Neuroanatomy: Principles and Methods, 2002); Bower and Bolouri (Computational Modeling of Genetic and Biochemical Networks, 2001); Hines et al. (J. Comput. Neurosci. 17, 7-11, 2004); Shepherd et al. (Trends Neurosci. 21, 460-468, 1998); Sivakumaran et al. (Bioinformatics 19, 408-415, 2003); Smolen et al. (Neuron 26, 567-580, 2000); Vadigepalli et al. (OMICS 7, 235-252, 2003)]. Models of neural systems provide quantitative and modifiable frameworks for representing data and analyzing neural function. These models can be developed and solved using neurosimulators. One such neurosimulator is simulator for neural networks and action potentials (SNNAP) [Ziv (J. Neurophysiol. 71, 294-308, 1994)]. SNNAP is a versatile and user-friendly tool for developing and simulating models of neurons and neural networks. SNNAP simulates many features of neuronal function, including ionic currents and their modulation by intracellular ions and/or second messengers, and synaptic transmission and synaptic plasticity. SNNAP is written in Java and runs on most computers. Moreover, SNNAP provides a graphical user interface (GUI) and does not require programming skills. This chapter describes several capabilities of SNNAP and illustrates methods for simulating neurons and neural networks. SNNAP is available at http://snnap.uth.tmc.edu .

  15. Central Configurations of the Curved N-Body Problem

    NASA Astrophysics Data System (ADS)

    Diacu, Florin; Stoica, Cristina; Zhu, Shuqiang

    2018-06-01

    We consider the N-body problem of celestial mechanics in spaces of nonzero constant curvature. Using the concept of effective potential, we define the moment of inertia for systems moving on spheres and hyperbolic spheres and show that we can recover the classical definition in the Euclidean case. After proving some criteria for the existence of relative equilibria, we find a natural way to define the concept of central configuration in curved spaces using the moment of inertia and show that our definition is formally similar to the one that governs the classical problem. We prove that, for any given point masses on spheres and hyperbolic spheres, central configurations always exist. We end with results concerning the number of central configurations that lie on the same geodesic, thus extending the celebrated theorem of Moulton to hyperbolic spheres and pointing out that it has no straightforward generalization to spheres, where the count gets complicated even for two bodies.

  16. The structure of distractor-response bindings: Conditions for configural and elemental integration.

    PubMed

    Moeller, Birte; Frings, Christian; Pfister, Roland

    2016-04-01

    Human action control is influenced by bindings between perceived stimuli and responses carried out in their presence. Notably, responses given to a target stimulus can also be integrated with additional response-irrelevant distractor stimuli that accompany the target (distractor-response binding). Subsequently reencountering such a distractor then retrieves the associated response. Although a large body of evidence supports the existence of this effect, the specific structure of distractor-response bindings is still unclear. Here, we test the predictions derived from 2 possible assumptions about the structure of bindings between distractors and responses. According to a configural approach, the entire distractor object is integrated with a response, and only upon repetition of the entire distractor object the associated response would be retrieved. According to an elemental approach, one would predict integration of individual distractor features with the response and retrieval due to the repetition of an individual distractor feature. Four experiments indicate that both, configural and elemental bindings exist and specify boundary conditions for each type of binding. These findings provide detailed insights into the architecture of bindings between response-irrelevant stimuli and actions and thus allow for specifying how distractor stimuli influence human behavior. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  17. Experimental investigation of plasma sheaths in magnetic mirror and cusp configurations

    NASA Astrophysics Data System (ADS)

    Jiang, Zhengqi; Wei, Zi-an; Ma, J. X.

    2017-11-01

    Sheath structures near a metal plate in a magnetized plasma were experimentally investigated in magnetic mirror and cusp configurations. Plasma parameters and the sheath potential distributions were probed by a planar and an emissive probe, respectively. The measured sheath profiles in the mirror configuration show that the sheath thickness first decreases and then increases when the magnetic strength is raised. A magnetic flux-tube model was used to explain this result. In the cusp configuration, the measured sheath thickness decreases with the increase of the coil current creating the magnetic cusp. However, when normalized by the electron Debye length, the dependence of the sheath thickness on the coil current is reversed.

  18. Comparison of genetically encoded calcium indicators for monitoring action potentials in mammalian brain by two-photon excitation fluorescence microscopy

    PubMed Central

    Podor, Borbala; Hu, Yi-ling; Ohkura, Masamichi; Nakai, Junichi; Croll, Roger; Fine, Alan

    2015-01-01

    Abstract. Imaging calcium transients associated with neuronal activity has yielded important insights into neural physiology. Genetically encoded calcium indicators (GECIs) offer conspicuous potential advantages for this purpose, including exquisite targeting. While the catalogue of available GECIs is steadily growing, many newly developed sensors that appear promising in vitro or in model cells appear to be less useful when expressed in mammalian neurons. We have, therefore, evaluated the performance of GECIs from two of the most promising families of sensors, G-CaMPs [Nat. Biotechnol. 19(2), 137–141 (2001)11175727] and GECOs [Science 333(6051), 1888–1891 (2011)21903779], for monitoring action potentials in rat brain. Specifically, we used two-photon excitation fluorescence microscopy to compare calcium transients detected by G-CaMP3; GCaMP6f; G-CaMP7; Green-GECO1.0, 1.1 and 1.2; Blue-GECO; Red-GECO; Rex-GECO0.9; Rex-GECO1; Carmine-GECO; Orange-GECO; and Yellow-GECO1s. After optimizing excitation wavelengths, we monitored fluorescence signals associated with increasing numbers of action potentials evoked by current injection in CA1 pyramidal neurons in rat organotypic hippocampal slices. Some GECIs, particularly Green-GECO1.2, GCaMP6f, and G-CaMP7, were able to detect single action potentials with high reliability. By virtue of greatest sensitivity and fast kinetics, G-CaMP7 may be the best currently available GECI for monitoring calcium transients in mammalian neurons. PMID:26158004

  19. Analysis of Advanced Rotorcraft Configurations

    NASA Technical Reports Server (NTRS)

    Johnson, Wayne

    2000-01-01

    Advanced rotorcraft configurations are being investigated with the objectives of identifying vehicles that are larger, quieter, and faster than current-generation rotorcraft. A large rotorcraft, carrying perhaps 150 passengers, could do much to alleviate airport capacity limitations, and a quiet rotorcraft is essential for community acceptance of the benefits of VTOL operations. A fast, long-range, long-endurance rotorcraft, notably the tilt-rotor configuration, will improve rotorcraft economics through productivity increases. A major part of the investigation of advanced rotorcraft configurations consists of conducting comprehensive analyses of vehicle behavior for the purpose of assessing vehicle potential and feasibility, as well as to establish the analytical models required to support the vehicle development. The analytical work of FY99 included applications to tilt-rotor aircraft. Tilt Rotor Aeroacoustic Model (TRAM) wind tunnel measurements are being compared with calculations performed by using the comprehensive analysis tool (Comprehensive Analytical Model of Rotorcraft Aerodynamics and Dynamics (CAMRAD 11)). The objective is to establish the wing and wake aerodynamic models that are required for tilt-rotor analysis and design. The TRAM test in the German-Dutch Wind Tunnel (DNW) produced extensive measurements. This is the first test to encompass air loads, performance, and structural load measurements on tilt rotors, as well as acoustic and flow visualization data. The correlation of measurements and calculations includes helicopter-mode operation (performance, air loads, and blade structural loads), hover (performance and air loads), and airplane-mode operation (performance).

  20. Prediction of Thorough QT study results using action potential simulations based on ion channel screens.

    PubMed

    Mirams, Gary R; Davies, Mark R; Brough, Stephen J; Bridgland-Taylor, Matthew H; Cui, Yi; Gavaghan, David J; Abi-Gerges, Najah

    2014-01-01

    Detection of drug-induced pro-arrhythmic risk is a primary concern for pharmaceutical companies and regulators. Increased risk is linked to prolongation of the QT interval on the body surface ECG. Recent studies have shown that multiple ion channel interactions can be required to predict changes in ventricular repolarisation and therefore QT intervals. In this study we attempt to predict the result of the human clinical Thorough QT (TQT) study, using multiple ion channel screening which is available early in drug development. Ion current reduction was measured, in the presence of marketed drugs which have had a TQT study, for channels encoded by hERG, CaV1.2, NaV1.5, KCNQ1/MinK, and Kv4.3/KChIP2.2. The screen was performed on two platforms - IonWorks Quattro (all 5 channels, 34 compounds), and IonWorks Barracuda (hERG & CaV1.2, 26 compounds). Concentration-effect curves were fitted to the resulting data, and used to calculate a percentage reduction in each current at a given concentration. Action potential simulations were then performed using the ten Tusscher and Panfilov (2006), Grandi et al. (2010) and O'Hara et al. (2011) human ventricular action potential models, pacing at 1Hz and running to steady state, for a range of concentrations. We compared simulated action potential duration predictions with the QT prolongation observed in the TQT studies. At the estimated concentrations, simulations tended to underestimate any observed QT prolongation. When considering a wider range of concentrations, and conventional patch clamp rather than screening data for hERG, prolongation of ≥5ms was predicted with up to 79% sensitivity and 100% specificity. This study provides a proof-of-principle for the prediction of human TQT study results using data available early in drug development. We highlight a number of areas that need refinement to improve the method's predictive power, but the results suggest that such approaches will provide a useful tool in cardiac safety

  1. Contribution of the Axon Initial Segment to Action Potentials Recorded Extracellularly.

    PubMed

    Teleńczuk, Maria; Brette, Romain; Destexhe, Alain; Teleńczuk, Bartosz

    2018-01-01

    Action potentials (APs) are electric phenomena that are recorded both intracellularly and extracellularly. APs are usually initiated in the short segment of the axon called the axon initial segment (AIS). It was recently proposed that at the onset of an AP the soma and the AIS form a dipole. We study the extracellular signature [the extracellular AP (EAP)] generated by such a dipole. First, we demonstrate the formation of the dipole and its extracellular signature in detailed morphological models of a reconstructed pyramidal neuron. Then, we study the EAP waveform and its spatial dependence in models with axonal AP initiation and contrast it with the EAP obtained in models with somatic AP initiation. We show that in the models with axonal AP initiation the dipole forms between somatodendritic compartments and the AIS, and not between soma and dendrites as in the classical models. The soma-dendrites dipole is present only in models with somatic AP initiation. Our study has consequences for interpreting extracellular recordings of single-neuron activity and determining electrophysiological neuron types, but also for better understanding the origins of the high-frequency macroscopic extracellular potentials recorded in the brain.

  2. Electrophysiological properties of computational human ventricular cell action potential models under acute ischemic conditions.

    PubMed

    Dutta, Sara; Mincholé, Ana; Quinn, T Alexander; Rodriguez, Blanca

    2017-10-01

    Acute myocardial ischemia is one of the main causes of sudden cardiac death. The mechanisms have been investigated primarily in experimental and computational studies using different animal species, but human studies remain scarce. In this study, we assess the ability of four human ventricular action potential models (ten Tusscher and Panfilov, 2006; Grandi et al., 2010; Carro et al., 2011; O'Hara et al., 2011) to simulate key electrophysiological consequences of acute myocardial ischemia in single cell and tissue simulations. We specifically focus on evaluating the effect of extracellular potassium concentration and activation of the ATP-sensitive inward-rectifying potassium current on action potential duration, post-repolarization refractoriness, and conduction velocity, as the most critical factors in determining reentry vulnerability during ischemia. Our results show that the Grandi and O'Hara models required modifications to reproduce expected ischemic changes, specifically modifying the intracellular potassium concentration in the Grandi model and the sodium current in the O'Hara model. With these modifications, the four human ventricular cell AP models analyzed in this study reproduce the electrophysiological alterations in repolarization, refractoriness, and conduction velocity caused by acute myocardial ischemia. However, quantitative differences are observed between the models and overall, the ten Tusscher and modified O'Hara models show closest agreement to experimental data. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  3. Feature-Specific Event-Related Potential Effects to Action- and Sound-Related Verbs during Visual Word Recognition

    PubMed Central

    Popp, Margot; Trumpp, Natalie M.; Kiefer, Markus

    2016-01-01

    Grounded cognition theories suggest that conceptual representations essentially depend on modality-specific sensory and motor systems. Feature-specific brain activation across different feature types such as action or audition has been intensively investigated in nouns, while feature-specific conceptual category differences in verbs mainly focused on body part specific effects. The present work aimed at assessing whether feature-specific event-related potential (ERP) differences between action and sound concepts, as previously observed in nouns, can also be found within the word class of verbs. In Experiment 1, participants were visually presented with carefully matched sound and action verbs within a lexical decision task, which provides implicit access to word meaning and minimizes strategic access to semantic word features. Experiment 2 tested whether pre-activating the verb concept in a context phase, in which the verb is presented with a related context noun, modulates subsequent feature-specific action vs. sound verb processing within the lexical decision task. In Experiment 1, ERP analyses revealed a differential ERP polarity pattern for action and sound verbs at parietal and central electrodes similar to previous results in nouns. Pre-activation of the meaning of verbs in the preceding context phase in Experiment 2 resulted in a polarity-reversal of feature-specific ERP effects in the lexical decision task compared with Experiment 1. This parallels analogous earlier findings for primed action and sound related nouns. In line with grounded cognitions theories, our ERP study provides evidence for a differential processing of action and sound verbs similar to earlier observation for concrete nouns. Although the localizational value of ERPs must be viewed with caution, our results indicate that the meaning of verbs is linked to different neural circuits depending on conceptual feature relevance. PMID:28018201

  4. Feature-Specific Event-Related Potential Effects to Action- and Sound-Related Verbs during Visual Word Recognition.

    PubMed

    Popp, Margot; Trumpp, Natalie M; Kiefer, Markus

    2016-01-01

    Grounded cognition theories suggest that conceptual representations essentially depend on modality-specific sensory and motor systems. Feature-specific brain activation across different feature types such as action or audition has been intensively investigated in nouns, while feature-specific conceptual category differences in verbs mainly focused on body part specific effects. The present work aimed at assessing whether feature-specific event-related potential (ERP) differences between action and sound concepts, as previously observed in nouns, can also be found within the word class of verbs. In Experiment 1, participants were visually presented with carefully matched sound and action verbs within a lexical decision task, which provides implicit access to word meaning and minimizes strategic access to semantic word features. Experiment 2 tested whether pre-activating the verb concept in a context phase, in which the verb is presented with a related context noun, modulates subsequent feature-specific action vs. sound verb processing within the lexical decision task. In Experiment 1, ERP analyses revealed a differential ERP polarity pattern for action and sound verbs at parietal and central electrodes similar to previous results in nouns. Pre-activation of the meaning of verbs in the preceding context phase in Experiment 2 resulted in a polarity-reversal of feature-specific ERP effects in the lexical decision task compared with Experiment 1. This parallels analogous earlier findings for primed action and sound related nouns. In line with grounded cognitions theories, our ERP study provides evidence for a differential processing of action and sound verbs similar to earlier observation for concrete nouns. Although the localizational value of ERPs must be viewed with caution, our results indicate that the meaning of verbs is linked to different neural circuits depending on conceptual feature relevance.

  5. Boron-doped nanocrystalline diamond microelectrode arrays monitor cardiac action potentials.

    PubMed

    Maybeck, Vanessa; Edgington, Robert; Bongrain, Alexandre; Welch, Joseph O; Scorsone, Emanuel; Bergonzo, Philippe; Jackman, Richard B; Offenhäusser, Andreas

    2014-02-01

    The expansion of diamond-based electronics in the area of biological interfacing has not been as thoroughly explored as applications in electrochemical sensing. However, the biocompatibility of diamond, large safe electrochemical window, stability, and tunable electronic properties provide opportunities to develop new devices for interfacing with electrogenic cells. Here, the fabrication of microelectrode arrays (MEAs) with boron-doped nanocrystalline diamond (BNCD) electrodes and their interfacing with cardiomyocyte-like HL-1 cells to detect cardiac action potentials are presented. A nonreductive means of structuring doped and undoped diamond on the same substrate is shown. The resulting BNCD electrodes show high stability under mechanical stress generated by the cells. It is shown that by fabricating the entire surface of the MEA with NCD, in patterns of conductive doped, and isolating undoped regions, signal detection may be improved up to four-fold over BNCD electrodes passivated with traditional isolators. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Distributed computing for membrane-based modeling of action potential propagation.

    PubMed

    Porras, D; Rogers, J M; Smith, W M; Pollard, A E

    2000-08-01

    Action potential propagation simulations with physiologic membrane currents and macroscopic tissue dimensions are computationally expensive. We, therefore, analyzed distributed computing schemes to reduce execution time in workstation clusters by parallelizing solutions with message passing. Four schemes were considered in two-dimensional monodomain simulations with the Beeler-Reuter membrane equations. Parallel speedups measured with each scheme were compared to theoretical speedups, recognizing the relationship between speedup and code portions that executed serially. A data decomposition scheme based on total ionic current provided the best performance. Analysis of communication latencies in that scheme led to a load-balancing algorithm in which measured speedups at 89 +/- 2% and 75 +/- 8% of theoretical speedups were achieved in homogeneous and heterogeneous clusters of workstations. Speedups in this scheme with the Luo-Rudy dynamic membrane equations exceeded 3.0 with eight distributed workstations. Cluster speedups were comparable to those measured during parallel execution on a shared memory machine.

  7. Effects of nerve growth factor on the action potential duration and repolarizing currents in a rabbit model of myocardial infarction

    PubMed Central

    Lan, Yun-Feng; Zhang, Jian-Cheng; Gao, Jin-Lao; Wang, Xue-Ping; Fang, Zhou; Fu, Yi-Cheng; Chen, Mei-Yan; Lin, Min; Xue, Qiao; Li, Yang

    2013-01-01

    Objectives To investigate the effect of nerve growth factor (NGF) on the action potential and potassium currents of non-infarcted myocardium in the myocardial infarcted rabbit model. Methods Rabbits with occlusion of the left anterior descending coronary artery were prepared and allowed to recover for eight weeks (healed myocardial infarction, HMI). During ligation surgery of the left coronary artery, a polyethylene tube was placed near the left stellate ganglion in the subcutis of the neck for the purpose of administering NGF 400 U/d for eight weeks (HMI + NGF group). Cardiomyocytes were isolated from regions of the non-infarcted left ventricular wall and the action potentials and ion currents in these cells were recorded using whole-cell patch clamps. Results Compared with HMI and control cardiomyocytes, significant prolongation of APD50 or APD90 (Action potential duration (APD) measured at 50% and 90% of repolarization) in HMI + NGF cardiomyocytes was found. The results showed that the 4-aminopyridine sensitive transient outward potassium current (Ito), the rapidly activated omponent of delayed rectifier potassium current (IKr), the slowly activated component of delayed rectifier potassium current (IKs), and the L-type calcium current (ICaL) were significantly altered in NGF + HMI cardiomyocytes compared with HMI and control cells. Conclusions Our results suggest that NGF treatment significantly prolongs APD in HMI cardiomyocytes and that a decrease in outward potassium currents and an increase of inward Ca2+ current are likely the underlying mechanism of action. PMID:23610573

  8. Effects of nerve growth factor on the action potential duration and repolarizing currents in a rabbit model of myocardial infarction.

    PubMed

    Lan, Yun-Feng; Zhang, Jian-Cheng; Gao, Jin-Lao; Wang, Xue-Ping; Fang, Zhou; Fu, Yi-Cheng; Chen, Mei-Yan; Lin, Min; Xue, Qiao; Li, Yang

    2013-03-01

    To investigate the effect of nerve growth factor (NGF) on the action potential and potassium currents of non-infarcted myocardium in the myocardial infarcted rabbit model. Rabbits with occlusion of the left anterior descending coronary artery were prepared and allowed to recover for eight weeks (healed myocardial infarction, HMI). During ligation surgery of the left coronary artery, a polyethylene tube was placed near the left stellate ganglion in the subcutis of the neck for the purpose of administering NGF 400 U/d for eight weeks (HMI + NGF group). Cardiomyocytes were isolated from regions of the non-infarcted left ventricular wall and the action potentials and ion currents in these cells were recorded using whole-cell patch clamps. Compared with HMI and control cardiomyocytes, significant prolongation of APD50 or APD90 (Action potential duration (APD) measured at 50% and 90% of repolarization) in HMI + NGF cardiomyocytes was found. The results showed that the 4-aminopyridine sensitive transient outward potassium current (I to), the rapidly activated omponent of delayed rectifier potassium current (I Kr), the slowly activated component of delayed rectifier potassium current (I Ks), and the L-type calcium current (I CaL) were significantly altered in NGF + HMI cardiomyocytes compared with HMI and control cells. Our results suggest that NGF treatment significantly prolongs APD in HMI cardiomyocytes and that a decrease in outward potassium currents and an increase of inward Ca(2+) current are likely the underlying mechanism of action.

  9. Silicon ribbon growth by a capillary action shaping technique

    NASA Technical Reports Server (NTRS)

    Schwuttke, G. H.; Ciszek, T. F.; Kran, A.; Yang, K.

    1977-01-01

    The crystal-growth method under investigation is a capillary action shaping technique. Meniscus shaping for the desired ribbon geometry occurs at the vertex of a wettable dye. As ribbon growth depletes the melt meniscus, capillary action supplies replacement material. The configuration of the technique used in our initial studies is shown. The crystal-growth method has been applied to silicon ribbons it was found that substantial improvements in ribbon surface quality could be achieved with a higher melt meniscus than that attainable with the EFG technique.

  10. Configuration optimization of space structures

    NASA Technical Reports Server (NTRS)

    Felippa, Carlos; Crivelli, Luis A.; Vandenbelt, David

    1991-01-01

    The objective is to develop a computer aid for the conceptual/initial design of aerospace structures, allowing configurations and shape to be apriori design variables. The topics are presented in viewgraph form and include the following: Kikuchi's homogenization method; a classical shape design problem; homogenization method steps; a 3D mechanical component design example; forming a homogenized finite element; a 2D optimization problem; treatment of volume inequality constraint; algorithms for the volume inequality constraint; object function derivatives--taking advantage of design locality; stiffness variations; variations of potential; and schematics of the optimization problem.

  11. Environmental Asthma Reduction Potential Estimates for Selected Mitigation Actions in Finland Using a Life Table Approach

    PubMed Central

    Rumrich, Isabell Katharina; Hänninen, Otto

    2015-01-01

    Aims: To quantify the reduction potential of asthma in Finland achievable by adjusting exposures to selected environmental factors. Methods: A life table model for the Finnish population for 1986–2040 was developed and Years Lived with Disability caused by asthma and attributable to the following selected exposures were estimated: tobacco smoke (smoking and second hand tobacco smoke), ambient fine particles, indoor dampness and mould, and pets. Results: At baseline (2011) about 25% of the total asthma burden was attributable to the selected exposures. Banning tobacco was the most efficient mitigation action, leading to 6% reduction of the asthma burden. A 50% reduction in exposure to dampness and mould as well as a doubling in exposure to pets lead each to a 2% reduction. Ban of urban small scale wood combustion, chosen as a mitigation action to reduce exposure to fine particles, leads to a reduction of less than 1% of the total asthma burden. Combination of the most efficient mitigation actions reduces the total asthma burden by 10%. A more feasible combination of mitigation actions leads to 6% reduction of the asthma burden. Conclusions: The adjustment of environmental exposures can reduce the asthma burden in Finland by up to 10%. PMID:26067987

  12. Fully unsteady subsonic and supersonic potential aerodynamics for complex aircraft configurations with applications to flutter

    NASA Technical Reports Server (NTRS)

    Tseng, K.; Morino, L.

    1975-01-01

    A general formulation is presented for the analysis of steady and unsteady, subsonic and supersonic aerodynamics for complex aircraft configurations. The theoretical formulation, the numerical procedure, the description of the program SOUSSA (steady, oscillatory and unsteady, subsonic and supersonic aerodynamics) and numerical results are included. In particular, generalized forces for fully unsteady (complex frequency) aerodynamics for a wing-body configuration, AGARD wing-tail interference in both subsonic and supersonic flows as well as flutter analysis results are included. The theoretical formulation is based upon an integral equation, which includes completely arbitrary motion. Steady and oscillatory aerodynamic flows are considered. Here small-amplitude, fully transient response in the time domain is considered. This yields the aerodynamic transfer function (Laplace transform of the fully unsteady operator) for frequency domain analysis. This is particularly convenient for the linear systems analysis of the whole aircraft.

  13. Double peak sensory nerve action potentials to single stimuli in nerve conduction studies.

    PubMed

    Leote, Joao; Pereira, Pedro; Valls-Sole, Josep

    2017-05-01

    In humans, sensory nerve action potentials (SNAPs) can show 2 separate deflections, i.e., double peak potentials (DPp), which necessarily means that 1 peak is delayed with respect to the other. DPps may have various origins and be due to either physical or physiological properties. We review the nature of commonly encountered DPps in clinical practice, provide the most likely interpretations for their physiological origin, and assess their reproducibility and clinical utility. We classified the DPps into 3 categories: (1) simultaneous anodal and cathodal stimulation. (2) simultaneous recording from 2 different nerves at the same site, and (3) SNAP desynchronization. Although the recording of DPps is not a standardized neurophysiological method, their study brings interesting cues about the physiology of nerve stimulation and paves the way for clinical application of such an observation. Muscle Nerve 55: 619-625, 2017. © 2016 Wiley Periodicals, Inc.

  14. Three-dimensional mapping and regulation of action potential propagation in nanoelectronics innervated tissues

    PubMed Central

    Dai, Xiaochuan; Zhou, Wei; Gao, Teng; Liu, Jia; Lieber, Charles M.

    2016-01-01

    Real-time mapping and manipulation of electrophysiology in three-dimensional (3D) tissues could impact broadly fundamental scientific and clinical studies, yet realization lacks effective methods. Here we introduce tissue-scaffold-mimicking 3D nanoelectronic arrays consisting of 64 addressable devices with subcellular dimensions and sub-millisecond time-resolution. Real-time extracellular action potential (AP) recordings reveal quantitative maps of AP propagation in 3D cardiac tissues, enable in situ tracing of the evolving topology of 3D conducting pathways in developing cardiac tissues, and probe the dynamics of AP conduction characteristics in a transient arrhythmia disease model and subsequent tissue self-adaptation. We further demonstrate simultaneous multi-site stimulation and mapping to manipulate actively the frequency and direction of AP propagation. These results establish new methodologies for 3D spatiotemporal tissue recording and control, and demonstrate the potential to impact regenerative medicine, pharmacology and electronic therapeutics. PMID:27347837

  15. Spin-orbit configuration interaction calculation of the potential energy curves of iodine oxide

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Roszak, S.; Krauss, M.; Alekseyev, A.B.

    2000-04-06

    An ab initio configuration interaction (CI) study including spin-orbit coupling is carried out for the ground and excited states of the IO radical by employing relativistic effective core potentials. The computed spectroscopic constants are in good agreement with available experimental data, with some tendency to underestimate the strength of bonding. The first excited state, a{sup 4}{Sigma}{sup {minus}}, which has not yet been observed experimentally, is predicted to be bound by 30.1 kJ/mol and to have a significantly larger equilibrium distance than the ground state. It is split by spin-orbit interaction into 1/2 and 3/2 components, with the 1/2 component beingmore » the lower one with a calculated spin-orbit splitting of 210 cm{sup {minus}1}. The most interesting state in the low-energy IO spectrum, A{sub 1}{sup 2}{Pi}{sub 3/2}, is shown to be predissociated due to interaction with a number of repulsive electronic states. Predissociation of the A{sup 1}, {nu}{prime} = 0, 1 vibrational levels is attributed to a fairly weak spin-orbit coupling with the {sup 2}{Delta}{sub 3/2} state, while rotationally dependent predissociation of the {nu}{prime} = 2 level is explained by the coupling with the 1/2(III) state having mainly {sup 2}{Sigma}{sup {minus}} character. Strong predissociation of the {nu}{prime} {ge} 4 levels is attributed to interaction with the higher-lying {Omega} = 3/2 states, with predominantly {sup 4}{Sigma}{sup +} and {sup 4}{Delta} origin.« less

  16. The linear synchronization measures of uterine EMG signals: Evidence of synchronized action potentials during propagation.

    PubMed

    Domino, Malgorzata; Pawlinski, Bartosz; Gajewski, Zdzislaw

    2016-11-01

    Evaluation of synchronization between myoelectric signals can give new insights into the functioning of the complex system of porcine myometrium. We propose a model of uterine contractions according to the hypothesis of action potentials similarity which is possible to detect during propagation in the uterine wall. We introduce similarity measures based on the concept of synchronization as used in matching linear signals such as electromyographic (EMG) time series data. The aim was to present linear measures to assess synchronization between contractions in different topographic regions of the uterus. We use the cross-correlation function (ƒx,y[l], ƒy,z[l]) and the cross-coherence function (Cxy[ƒ], Cyz[ƒ]) to assess synchronization between three data series of a diestral uterine EMG bundles in porcine reproductive tract. Spontaneous uterine activity was recorded using telemetry method directly by three-channel transmitter and three silver bipolar needle electrodes sutured on different topographic regions of the reproductive tract in the sow. The results show the usefulness of the cross-coherence function in that synchronization between uterine horn and corpus uteri for multiple action potentials (bundles) could be observed. The EMG bundles synchronization may be used to investigate the direction and velocity of EMG signals propagation in porcine reproductive tract. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Configurational entropy of critical earthquake populations

    NASA Astrophysics Data System (ADS)

    Goltz, C.; Böse, M.

    2002-10-01

    We present an approach to describe the evolution of distributed seismicity by configurational entropy. We demonstrate the detection of phase transitions in the sense of a critical point phenomenon in a 2D site-percolation model and in temporal and spatial vicinity to the 1992, M7.3 Landers earthquake in Southern California. Our findings support the assumption of intermittent criticality in the Earth's crust. We also address the potential usefulness of the method for earthquake catalogue declustering.

  18. Microneurography in rats: a minimally invasive method to record single C-fiber action potentials from peripheral nerves in vivo.

    PubMed

    Serra, Jordi; Bostock, Hugh; Navarro, Xavier

    2010-02-19

    Microneurography is a method suitable for recording intraneural single or multiunit action potentials in conscious subjects. Microneurography has rarely been applied to animal experiments, where more invasive methods, like the teased fiber recording technique, are widely used. We have tested the feasibility of microneurographic recordings from the peripheral nerves of rats. Tungsten microelectrodes were inserted into the sciatic nerve at mid-thigh level. Single or multiunit action potentials evoked by regular electrical stimulation were recorded, digitized and displayed as a raster plot of latencies. The method allows unambiguous recording and recognition of single C-fiber action potentials from an in vivo preparation, with minimal disruption of the nerve being recorded. Multiple C-fibers can be recorded simultaneously for several hours, and if the animal is allowed to recover, repeated recording sessions can be obtained from the same nerve at the same level over a period of weeks or months. Also, single C units can be functionally identified by their changes in latency to natural stimuli, and insensitive units can be recognized as 'silent' nociceptors or sympathetic efferents by their distinctive profiles of activity-dependent slowing during repetitive electrical stimulation, or by the effect on spontaneous efferent activity of a proximal anesthetic block. Moreover, information about the biophysical properties of C axons can be obtained from their latency recovery cycles. Finally, we show that this preparation is potentially suitable for the study of C-fiber behavior in models of neuropathies and nerve lesions, both under resting conditions and in response to drug administration.

  19. Modeling cardiac action potential shortening driven by oxidative stress-induced mitochondrial oscillations in guinea pig cardiomyocytes.

    PubMed

    Zhou, Lufang; Cortassa, Sonia; Wei, An-Chi; Aon, Miguel A; Winslow, Raimond L; O'Rourke, Brian

    2009-10-07

    Ischemia-induced shortening of the cardiac action potential and its heterogeneous recovery upon reperfusion are thought to set the stage for reentrant arrhythmias and sudden cardiac death. We have recently reported that the collapse of mitochondrial membrane potential (DeltaPsi(m)) through a mechanism triggered by reactive oxygen species (ROS), coupled to the opening of sarcolemmal ATP-sensitive potassium (K(ATP)) channels, contributes to electrical dysfunction during ischemia-reperfusion. Here we present a computational model of excitation-contraction coupling linked to mitochondrial bioenergetics that incorporates mitochondrial ROS-induced ROS release with coupling between the mitochondrial energy state and electrical excitability mediated by the sarcolemmal K(ATP) current (I(K,ATP)). Whole-cell model simulations demonstrate that increasing the fraction of oxygen diverted from the respiratory chain to ROS production triggers limit-cycle oscillations of DeltaPsi(m), redox potential, and mitochondrial respiration through the activation of a ROS-sensitive inner membrane anion channel. The periods of transient mitochondrial uncoupling decrease the cytosolic ATP/ADP ratio and activate I(K,ATP), consequently shortening the cellular action potential duration and ultimately suppressing electrical excitability. The model simulates emergent behavior observed in cardiomyocytes subjected to metabolic stress and provides a new tool for examining how alterations in mitochondrial oxidative phosphorylation will impact the electrophysiological, contractile, and Ca(2+) handling properties of the cardiac cell. Moreover, the model is an important step toward building multiscale models that will permit investigation of the role of spatiotemporal heterogeneity of mitochondrial metabolism in the mechanisms of arrhythmogenesis and contractile dysfunction in cardiac muscle.

  20. Overexpression of the Large-Conductance, Ca2+-Activated K+ (BK) Channel Shortens Action Potential Duration in HL-1 Cardiomyocytes.

    PubMed

    Stimers, Joseph R; Song, Li; Rusch, Nancy J; Rhee, Sung W

    2015-01-01

    Long QT syndrome is characterized by a prolongation of the interval between the Q wave and the T wave on the electrocardiogram. This abnormality reflects a prolongation of the ventricular action potential caused by a number of genetic mutations or a variety of drugs. Since effective treatments are unavailable, we explored the possibility of using cardiac expression of the large-conductance, Ca2+-activated K+ (BK) channel to shorten action potential duration (APD). We hypothesized that expression of the pore-forming α subunit of human BK channels (hBKα) in HL-1 cells would shorten action potential duration in this mouse atrial cell line. Expression of hBKα had minimal effects on expression levels of other ion channels with the exception of a small but significant reduction in Kv11.1. Patch-clamped hBKα expressing HL-1 cells exhibited an outward voltage- and Ca2+-sensitive K+ current, which was inhibited by the BK channel blocker iberiotoxin (100 nM). This BK current phenotype was not detected in untransfected HL-1 cells or in HL-1 null cells sham-transfected with an empty vector. Importantly, APD in hBKα-expressing HL-1 cells averaged 14.3 ± 2.8 ms (n = 10), which represented a 53% reduction in APD compared to HL-1 null cells lacking BKα expression. APD in the latter cells averaged 31.0 ± 5.1 ms (n = 13). The shortened APD in hBKα-expressing cells was restored to normal duration by 100 nM iberiotoxin, suggesting that a repolarizing K+ current attributed to BK channels accounted for action potential shortening. These findings provide initial proof-of-concept that the introduction of hBKα channels into a cardiac cell line can shorten APD, and raise the possibility that gene-based interventions to increase hBKα channels in cardiac cells may hold promise as a therapeutic strategy for long QT syndrome.

  1. Motor evoked potentials and compound muscle action potentials as prognostic tools for neonates with spina bifida.

    PubMed

    Cuppen, Inge; Geerdink, Niels; Rotteveel, Jan J; Mullaart, Reinier; Roeleveld, Nel; Pasman, Jaco W

    2013-03-01

    MEPs and CMAPs as prognostic tools for spina bifida. The aim of this prospective study was to determine the prognostic value of neurophysiological investigations compared to clinical neurological examination in infants with spina bifida. Thirty-six neonates born with spina bifida between 2002 and 2007 were evaluated and followed for 2 years. Lumbar motor evoked potentials (MEPs) and compound muscle action potentials (CMAPs) were obtained at the median age of 2 days old before surgical closure of the spinal anomaly. MEPs were recorded from the quadriceps femoris, tibialis anterior, and gastrocnemius muscles and CMAPs from the latter two muscles. Areas under the curve and latencies of the MEPs and CMAPs were measured. Clinical neurological outcome at the age of 2 years was described using Muscle Function Classes (MFCs) and ambulation status. The areas under the curve of MEPs and CMAPs in the legs were associated with lower neonatal levels of motor and sensory impairment. Better muscle function class of the lower limbs at 2 years of age was associated with larger MEP and CMAP areas of the gastrocnemius and tibialis anterior muscles at neonatal age. MEPs and CMAPs of the gastrocnemius and tibialis anterior muscles are of prognostic value for clinical neurological outcome in neonates born with spina bifida. Copyright © 2012 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

  2. Encoding of point of view during action observation in the local field potentials of macaque area F5.

    PubMed

    Caggiano, Vittorio; Giese, Martin; Thier, Peter; Casile, Antonino

    2015-02-01

    The discovery of mirror neurons compellingly shows that the monkey premotor area F5 is active not only during the execution but also during the observation of goal-directed motor acts. Previous studies have addressed the functioning of the mirror-neuron system at the single-unit level. Here, we tackled this research question at the network level by analysing local field potentials in area F5 while the monkey was presented with goal-directed actions executed by a human or monkey actor and observed either from a first-person or third-person perspective. Our analysis showed that rhythmic responses are not only present in area F5 during action observation, but are also modulated by the point of view. Observing an action from a subjective point of view produced significantly higher power in the low-frequency band (2-10 Hz) than observing the same action from a frontal view. Interestingly, an increase in power in the 2-10 Hz band was also produced by the execution of goal-directed motor acts. Independently of the point of view, action observation also produced a significant decrease in power in the 15-40 Hz band and an increase in the 60-100 Hz band. These results suggest that, depending on the point of view, action observation might activate different processes in area F5. Furthermore, they may provide information about the functional architecture of action perception in primates. © 2014 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  3. Spikelets in Pyramidal Neurons: Action Potentials Initiated in the Axon Initial Segment That Do Not Activate the Soma.

    PubMed

    Michalikova, Martina; Remme, Michiel W H; Kempter, Richard

    2017-01-01

    Spikelets are small spike-like depolarizations that can be measured in somatic intracellular recordings. Their origin in pyramidal neurons remains controversial. To explain spikelet generation, we propose a novel single-cell mechanism: somato-dendritic input generates action potentials at the axon initial segment that may fail to activate the soma and manifest as somatic spikelets. Using mathematical analysis and numerical simulations of compartmental neuron models, we identified four key factors controlling spikelet generation: (1) difference in firing threshold, (2) impedance mismatch, and (3) electrotonic separation between the soma and the axon initial segment, as well as (4) input amplitude. Because spikelets involve forward propagation of action potentials along the axon while they avoid full depolarization of the somato-dendritic compartments, we conjecture that this mode of operation saves energy and regulates dendritic plasticity while still allowing for a read-out of results of neuronal computations.

  4. Leptin alters somatosensory thalamic networks by decreasing gaba release from reticular thalamic nucleus and action potential frequency at ventrobasal neurons.

    PubMed

    Perissinotti, Paula P; Rivero-Echeto, María Celeste; Garcia-Rill, Edgar; Bisagno, Verónica; Urbano, Francisco J

    2018-06-01

    Leptin is an adipose-derived hormone that controls appetite and energy expenditure. Leptin receptors are expressed on extra-hypothalamic ventrobasal (VB) and reticular thalamic (RTN) nuclei from embryonic stages. Here, we studied the effects of pressure-puff, local application of leptin on both synaptic transmission and action potential properties of thalamic neurons in thalamocortical slices. We used whole-cell patch-clamp recordings of thalamocortical VB neurons from wild-type (WT) and leptin-deficient obese (ob/ob) mice. We observed differences in VB neurons action potentials and synaptic currents kinetics when comparing WT vs. ob/ob. Leptin reduced GABA release onto VB neurons throughout the activation of a JAK2-dependent pathway, without affecting excitatory glutamate transmission. We observed a rapid and reversible reduction by leptin of the number of action potentials of VB neurons via the activation of large conductance Ca 2+ -dependent potassium channels. These leptin effects were observed in thalamocortical slices from up to 5-week-old WT but not in leptin-deficient obese mice. Results described here suggest the existence of a leptin-mediated trophic modulation of thalamocortical excitability during postnatal development. These findings could contribute to a better understanding of leptin within the thalamocortical system and sleep deficits in obesity.

  5. Isosteviol prevents the prolongation of action potential in hypertrophied cardiomyoctyes by regulating transient outward potassium and L-type calcium channels.

    PubMed

    Fan, Zhuo; Lv, Nanying; Luo, Xiao; Tan, Wen

    2017-10-01

    Cardiac hypertrophy is a thickening of the heart muscle that is associated with cardiovascular diseases such as hypertension and myocardial infarction. It occurs initially as an adaptive process against increased workloads and often leads to sudden arrhythmic deaths. Studies suggest that the lethal arrhythmia is attributed to hypertrophy-induced destabilization of cardiac electrical activity, especially the prolongation of the action potential. The reduced activity of I to is demonstrated to be responsible for the ionic mechanism of prolonged action potential duration and arrhythmogeneity. Isosteviol (STV), a derivative of stevioside, plays a protective role in a variety of stress-induced cardiac diseases. Here we report effects of STV on rat ISO-induced hypertrophic cardiomyocytes. STV alleviated ISO-induced hypertrophy of cardiomyocytes by decreasing cell area of hypertrophied cardiomyocytes. STV application prevented the prolongation of action potential which was prominent in hypertrophied cells. The decrease and increase of current densities for I to and I CaL observed in hypertrophied myocytes were both prevented by STV application. In addition, the results of qRT-PCR suggested that the changes of electrophysiological activity of I to and I CaL are correlated to the alterations of the mRNA transcription level. Copyright © 2017. Published by Elsevier B.V.

  6. Electrically evoked compound action potentials are different depending on the site of cochlear stimulation.

    PubMed

    van de Heyning, Paul; Arauz, Santiago L; Atlas, Marcus; Baumgartner, Wolf-Dieter; Caversaccio, Marco; Chester-Browne, Ronel; Estienne, Patricia; Gavilan, Javier; Godey, Benoit; Gstöttner, Wolfgang; Han, Demin; Hagen, Rudolph; Kompis, Martin; Kuzovkov, Vlad; Lassaletta, Luis; Lefevre, Franc; Li, Yongxin; Müller, Joachim; Parnes, Lorne; Kleine Punte, Andrea; Raine, Christopher; Rajan, Gunesh; Rivas, Adriana; Rivas, José Antonio; Royle, Nicola; Sprinzl, Georg; Stephan, Kurt; Walkowiak, Adam; Yanov, Yuri; Zimmermann, Kim; Zorowka, Patrick; Skarzynski, Henryk

    2016-11-01

    One of the many parameters that can affect cochlear implant (CI) users' performance is the site of presentation of electrical stimulation, from the CI, to the auditory nerve. Evoked compound action potential (ECAP) measurements are commonly used to verify nerve function by stimulating one electrode contact in the cochlea and recording the resulting action potentials on the other contacts of the electrode array. The present study aimed to determine if the ECAP amplitude differs between the apical, middle, and basal region of the cochlea, if double peak potentials were more likely in the apex than the basal region of the cochlea, and if there were differences in the ECAP threshold and recovery function across the cochlea. ECAP measurements were performed in the apical, middle, and basal region of the cochlea at fixed sites of stimulation with varying recording electrodes. One hundred and forty one adult subjects with severe to profound sensorineural hearing loss fitted with a Standard or FLEX SOFT electrode were included in this study. ECAP responses were captured using MAESTRO System Software (MED-EL). The ECAP amplitude, threshold, and slope were determined using amplitude growth sequences. The 50% recovery rate was assessed using independent single sequences that have two stimulation pulses (a masker and a probe pulse) separated by a variable inter-pulse interval. For all recordings, ECAP peaks were annotated semi-automatically. ECAP amplitudes were greater upon stimulation of the apical region compared to the basal region of the cochlea. ECAP slopes were steeper in the apical region compared to the basal region of the cochlea and ECAP thresholds were lower in the middle region compared to the basal region of the cochlea. The incidence of double peaks was greater upon stimulation of the apical region compared to the basal region of the cochlea. This data indicates that the site and intensity of cochlear stimulation affect ECAP properties.

  7. Turning intractable counting into sampling: Computing the configurational entropy of three-dimensional jammed packings.

    PubMed

    Martiniani, Stefano; Schrenk, K Julian; Stevenson, Jacob D; Wales, David J; Frenkel, Daan

    2016-01-01

    We present a numerical calculation of the total number of disordered jammed configurations Ω of N repulsive, three-dimensional spheres in a fixed volume V. To make these calculations tractable, we increase the computational efficiency of the approach of Xu et al. [Phys. Rev. Lett. 106, 245502 (2011)10.1103/PhysRevLett.106.245502] and Asenjo et al. [Phys. Rev. Lett. 112, 098002 (2014)10.1103/PhysRevLett.112.098002] and we extend the method to allow computation of the configurational entropy as a function of pressure. The approach that we use computes the configurational entropy by sampling the absolute volume of basins of attraction of the stable packings in the potential energy landscape. We find a surprisingly strong correlation between the pressure of a configuration and the volume of its basin of attraction in the potential energy landscape. This relation is well described by a power law. Our methodology to compute the number of minima in the potential energy landscape should be applicable to a wide range of other enumeration problems in statistical physics, string theory, cosmology, and machine learning that aim to find the distribution of the extrema of a scalar cost function that depends on many degrees of freedom.

  8. TranAir: A full-potential, solution-adaptive, rectangular grid code for predicting subsonic, transonic, and supersonic flows about arbitrary configurations. Theory document

    NASA Technical Reports Server (NTRS)

    Johnson, F. T.; Samant, S. S.; Bieterman, M. B.; Melvin, R. G.; Young, D. P.; Bussoletti, J. E.; Hilmes, C. L.

    1992-01-01

    A new computer program, called TranAir, for analyzing complex configurations in transonic flow (with subsonic or supersonic freestream) was developed. This program provides accurate and efficient simulations of nonlinear aerodynamic flows about arbitrary geometries with the ease and flexibility of a typical panel method program. The numerical method implemented in TranAir is described. The method solves the full potential equation subject to a set of general boundary conditions and can handle regions with differing total pressure and temperature. The boundary value problem is discretized using the finite element method on a locally refined rectangular grid. The grid is automatically constructed by the code and is superimposed on the boundary described by networks of panels; thus no surface fitted grid generation is required. The nonlinear discrete system arising from the finite element method is solved using a preconditioned Krylov subspace method embedded in an inexact Newton method. The solution is obtained on a sequence of successively refined grids which are either constructed adaptively based on estimated solution errors or are predetermined based on user inputs. Many results obtained by using TranAir to analyze aerodynamic configurations are presented.

  9. Effects of acoustic noise on the auditory nerve compound action potentials evoked by electric pulse trains.

    PubMed

    Nourski, Kirill V; Abbas, Paul J; Miller, Charles A; Robinson, Barbara K; Jeng, Fuh-Cherng

    2005-04-01

    This study investigated the effects of acoustic noise on the auditory nerve compound action potentials in response to electric pulse trains. Subjects were adult guinea pigs, implanted with a minimally invasive electrode to preserve acoustic sensitivity. Electrically evoked compound action potentials (ECAP) were recorded from the auditory nerve trunk in response to electric pulse trains both during and after the presentation of acoustic white noise. Simultaneously presented acoustic noise produced a decrease in ECAP amplitude. The effect of the acoustic masker on the electric probe was greatest at the onset of the acoustic stimulus and it was followed by a partial recovery of the ECAP amplitude. Following cessation of the acoustic noise, ECAP amplitude recovered over a period of approximately 100-200 ms. The effects of the acoustic noise were more prominent at lower electric pulse rates (interpulse intervals of 3 ms and higher). At higher pulse rates, the ECAP adaptation to the electric pulse train alone was larger and the acoustic noise, when presented, produced little additional effect. The observed effects of noise on ECAP were the greatest at high electric stimulus levels and, for a particular electric stimulus level, at high acoustic noise levels.

  10. Estradiol-modified prolactin secretion independently of action potentials and Ca2+ and blockade of outward potassium currents in GH3 cells.

    PubMed

    Sánchez, Manuel; Suárez, Lorena; Cantabrana, Begoña; Bordallo, Javier

    2017-01-01

    Estrogens facilitate prolactin (PRL) secretion acting on pituitary cells. In GH 3 cells, estradiol induces acute action potentials and oscillations of intracellular Ca 2+ associated with the secretagogue function. Estradiol modulates several ion channels which may affect the action potential rate and the release of PRL in lactotroph cells, which might depend on its concentration. The aims were to characterize the acute effect of supraphysiological concentrations of estradiol on Ca 2+ and noninactivating K + currents and measure the effect on the spontaneous action potentials and PRL release in the somatolactotroph cell line, GH 3 . Electrophysiological studies were carried out by voltage- and current-clamp techniques and ELISA determination of PRL secretion. Pharmacological concentrations of estradiol (above 1 μM), without a latency period, blocked Ca 2+ channels and noninactivating K + currents, including the large-conductance voltage- and Ca 2+ -activated K + channels (BK), studied in whole-cell nystatin perforated and in excided inside-out patches of GH 3 and CHO cells, transiently transfected with the human α-pore forming subunit of BK. The effect on BK was contrary to the agonist effect associated with the regulatory β 1 -subunits of the BK, which GH 3 cells lack, but its transient transfection did not modify the noninactivating current blockade, suggesting a different mechanism of regulation. Estradiol, at the same concentration range, acutely decreased the frequency of action potentials, an expected effect as consequence of the Ca 2+ channel blockade. Despite this, PRL secretion initially increased, followed by a decrease in long-term incubations. This suggests that, in GH 3 cells, supraphysiological concentrations of estradiol modulating PRL secretion are partially independent of extracellular Ca 2+ influx.

  11. Molecular motions that shape the cardiac action potential: Insights from voltage clamp fluorometry.

    PubMed

    Zhu, Wandi; Varga, Zoltan; Silva, Jonathan R

    2016-01-01

    Very recently, voltage-clamp fluorometry (VCF) protocols have been developed to observe the membrane proteins responsible for carrying the ventricular ionic currents that form the action potential (AP), including those carried by the cardiac Na(+) channel, NaV1.5, the L-type Ca(2+) channel, CaV1.2, the Na(+)/K(+) ATPase, and the rapid and slow components of the delayed rectifier, KV11.1 and KV7.1. This development is significant, because VCF enables simultaneous observation of ionic current kinetics with conformational changes occurring within specific channel domains. The ability gained from VCF, to connect nanoscale molecular movement to ion channel function has revealed how the voltage-sensing domains (VSDs) control ion flux through channel pores, mechanisms of post-translational regulation and the molecular pathology of inherited mutations. In the future, we expect that this data will be of great use for the creation of multi-scale computational AP models that explicitly represent ion channel conformations, connecting molecular, cell and tissue electrophysiology. Here, we review the VCF protocol, recent results, and discuss potential future developments, including potential use of these experimental findings to create novel computational models. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Modulation of KCNQ1 alternative splicing regulates cardiac IKs and action potential repolarization.

    PubMed

    Lee, Hsiang-Chun; Rudy, Yoram; Po-Yuan, Phd; Sheu, Sheng-Hsiung; Chang, Jan-Gowth; Cui, Jianmin

    2013-08-01

    Slow delayed-rectifier potassium current (IKs) channels, made of the pore-forming KCNQ1 and auxiliary KCNE1 subunits, play a key role in determining action potential duration (APD) in cardiac myocytes. The consequences of drug-induced KCNQ1 splice alteration remain unknown. To study the modulation of KCNQ1 alternative splicing by amiloride and the consequent changes in IKs and action potentials (APs) in ventricular myocytes. Canine endocardial, midmyocardial, and epicardial ventricular myocytes were isolated. Levels of KCNQ1a and KCNQ1b as well as a series of splicing factors were quantified by using the reverse transcriptase-polymerase chain reaction and Western blot. The effect of amiloride-induced changes in the KCNQ1b/total KCNQ1 ratio on AP was measured by using whole-cell patch clamp with and without isoproterenol. With 50 μmol/L of amiloride for 6 hours, KCNQ1a at transcriptional and translational levels increased in midmyocardial myocytes but decreased in endo- and epicardial myocytes. Likewise, changes in splicing factors in midmyocardial were opposite to that in endo- and epicardial myocytes. In midmyocardial myocytes amiloride shortened APD and decreased isoproterenol-induced early afterdepolarizations significantly. The same amiloride-induced effects were demonstrated by using human ventricular myocyte model for AP simulations under beta-adrenergic stimulation. Moreover, amiloride reduced the transmural dispersion of repolarization in pseudo-electrocardiogram. Amiloride regulates IKs and APs with transmural differences and reduces arrhythmogenicity through the modulation of KCNQ1 splicing. We suggested that the modulation of KCNQ1 splicing may help prevent arrhythmia. Copyright © 2013 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

  13. Three-dimensional mapping and regulation of action potential propagation in nanoelectronics-innervated tissues.

    PubMed

    Dai, Xiaochuan; Zhou, Wei; Gao, Teng; Liu, Jia; Lieber, Charles M

    2016-09-01

    Real-time mapping and manipulation of electrophysiology in three-dimensional (3D) tissues could have important impacts on fundamental scientific and clinical studies, yet realization is hampered by a lack of effective methods. Here we introduce tissue-scaffold-mimicking 3D nanoelectronic arrays consisting of 64 addressable devices with subcellular dimensions and a submillisecond temporal resolution. Real-time extracellular action potential (AP) recordings reveal quantitative maps of AP propagation in 3D cardiac tissues, enable in situ tracing of the evolving topology of 3D conducting pathways in developing cardiac tissues and probe the dynamics of AP conduction characteristics in a transient arrhythmia disease model and subsequent tissue self-adaptation. We further demonstrate simultaneous multisite stimulation and mapping to actively manipulate the frequency and direction of AP propagation. These results establish new methodologies for 3D spatiotemporal tissue recording and control, and demonstrate the potential to impact regenerative medicine, pharmacology and electronic therapeutics.

  14. Soliton configurations in generalized Mie electrodynamics

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Rybakov, Yu. P., E-mail: soliton4@mail.ru

    2011-07-15

    The generalization of the Mie electrodynamics within the scope of the effective 8-spinor field model is suggested, with the Lagrangian including Higgs-like potential and higher degrees of the invariant A{sub Micro-Sign }A{sup Micro-Sign }. Using special Brioschi 8-spinor identity, we show that the model includes the Skyrme and the Faddeev models as particular cases. We investigate the large-distance asymptotic of static solutions and estimate the electromagnetic contribution to the energy of the localized charged configuration.

  15. Electrically evoked compound action potentials recorded from the sheep spinal cord.

    PubMed

    Parker, John L; Karantonis, Dean M; Single, Peter S; Obradovic, Milan; Laird, James; Gorman, Robert B; Ladd, Leigh A; Cousins, Michael J

    2013-01-01

    The study aims to characterize the electrical response of dorsal column axons to depolarizing stimuli to help understand the mechanisms of spinal cord stimulation (SCS) for the relief of chronic pain. We recorded electrically evoked compound action potentials (ECAPs) during SCS in 10 anesthetized sheep using stimulating and recording electrodes on the same epidural SCS leads. A novel stimulating and recording system allowed artifact contamination of the ECAP to be minimized. The ECAP in the sheep spinal cord demonstrates a triphasic morphology, with P1, N1, and P2 peaks. The amplitude of the ECAP varies along the length of the spinal cord, with minimum amplitudes recorded from electrodes positioned over each intervertebral disc, and maximum amplitudes recorded in the midvertebral positions. This anatomically correlated depression of ECAP also correlates with the areas of the spinal cord with the highest thresholds for stimulation; thus regions of weakest response invariably had least sensitivity to stimulation by as much as a factor of two. The choice of stimulating electrode location can therefore have a profound effect on the power consumption for an implanted stimulator for SCS. There may be optimal positions for stimulation in the sheep, and this observation may translate to humans. Almost no change in conduction velocity (∼100 ms) was observed with increasing currents from threshold to twice threshold, despite increased Aβ fiber recruitment. Amplitude of sheep Aβ fiber potentials during SCS exhibit dependence on electrode location, highlighting potential optimization of Aβ recruitment and power consumption in SCS devices. © 2013 International Neuromodulation Society.

  16. Are conservation organizations configured for effective adaptation to global change?

    USGS Publications Warehouse

    Armsworth, Paul R.; Larson, Eric R.; Jackson, Stephen T.; Sax, Dov F.; Simonin, Paul W.; Blossey, Bernd; Green, Nancy; Lester, Liza; Klein, Mary L.; Ricketts, Taylor H.; Runge, Michael C.; Shaw, M. Rebecca

    2015-01-01

    Conservation organizations must adapt to respond to the ecological impacts of global change. Numerous changes to conservation actions (eg facilitated ecological transitions, managed relocations, or increased corridor development) have been recommended, but some institutional restructuring within organizations may also be needed. Here we discuss the capacity of conservation organizations to adapt to changing environmental conditions, focusing primarily on public agencies and nonprofits active in land protection and management in the US. After first reviewing how these organizations anticipate and detect impacts affecting target species and ecosystems, we then discuss whether they are sufficiently flexible to prepare and respond by reallocating funding, staff, or other resources. We raise new hypotheses about how the configuration of different organizations enables them to protect particular conservation targets and manage for particular biophysical changes that require coordinated management actions over different spatial and temporal scales. Finally, we provide a discussion resource to help conservation organizations assess their capacity to adapt.

  17. Accuracy of measurement in electrically evoked compound action potentials.

    PubMed

    Hey, Matthias; Müller-Deile, Joachim

    2015-01-15

    Electrically evoked compound action potentials (ECAP) in cochlear implant (CI) patients are characterized by the amplitude of the N1P1 complex. The measurement of evoked potentials yields a combination of the measured signal with various noise components but for ECAP procedures performed in the clinical routine, only the averaged curve is accessible. To date no detailed analysis of error dimension has been published. The aim of this study was to determine the error of the N1P1 amplitude and to determine the factors that impact the outcome. Measurements were performed on 32 CI patients with either CI24RE (CA) or CI512 implants using the Software Custom Sound EP (Cochlear). N1P1 error approximation of non-averaged raw data consisting of recorded single-sweeps was compared to methods of error approximation based on mean curves. The error approximation of the N1P1 amplitude using averaged data showed comparable results to single-point error estimation. The error of the N1P1 amplitude depends on the number of averaging steps and amplification; in contrast, the error of the N1P1 amplitude is not dependent on the stimulus intensity. Single-point error showed smaller N1P1 error and better coincidence with 1/√(N) function (N is the number of measured sweeps) compared to the known maximum-minimum criterion. Evaluation of N1P1 amplitude should be accompanied by indication of its error. The retrospective approximation of this measurement error from the averaged data available in clinically used software is possible and best done utilizing the D-trace in forward masking artefact reduction mode (no stimulation applied and recording contains only the switch-on-artefact). Copyright © 2014 Elsevier B.V. All rights reserved.

  18. Transverse versus longitudinal tripolar configuration for selective stimulation with multipolar cuff electrodes.

    PubMed

    Nielsen, Thomas N; Kurstjens, G A Mathijs; Struijk, Johannes J

    2011-04-01

    The ability to stimulate subareas of a nerve selectively is highly desirable, since it has the potential of simplifying surgery to implanting one cuff on a large nerve instead of many cuffs on smaller nerves or muscles, or alternatively can improve function where surgical access to the smaller nerves is limited. In this paper, stimulation was performed with a four-channel multipolar cuff electrode implanted on the sciatic nerve of nine rabbits to compare the extensively researched longitudinal tripolar configuration with the transverse tripolar configuration, which has received less interest. The performance of these configurations was evaluated in terms of selectivity in recruitment of the three branches of the sciatic nerve. The results showed that the transverse configuration was able to selectively activate the sciatic nerve branches to a functionally relevant level in more cases than the longitudinal configuration (20/27 versus 11/27 branches) and overall achieved a higher mean selectivity [0.79 ± 0.13 versus 0.61 ± 0.09 (mean ± standard deviation)]. The transverse configuration was most successful at recruiting the small cutaneous and medium-sized peroneal branches, and less successful at recruiting the large tibial nerve.

  19. Decision Making Configurations: An Alternative to the Centralization/Decentralization Conceptualization.

    ERIC Educational Resources Information Center

    Cullen, John B.; Perrewe, Pamela L.

    1981-01-01

    Used factors identified in the literature as predictors of centralization/decentralization as potential discriminating variables among several decision making configurations in university affiliated professional schools. The model developed from multiple discriminant analysis had reasonable success in classifying correctly only the decentralized…

  20. Application of optical action potentials in human induced pluripotent stem cells-derived cardiomyocytes to predict drug-induced cardiac arrhythmias.

    PubMed

    Lu, H R; Hortigon-Vinagre, M P; Zamora, V; Kopljar, I; De Bondt, A; Gallacher, D J; Smith, G

    2017-09-01

    Human induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs) are emerging as new and human-relevant source in vitro model for cardiac safety assessment that allow us to investigate a set of 20 reference drugs for predicting cardiac arrhythmogenic liability using optical action potential (oAP) assay. Here, we describe our examination of the oAP measurement using a voltage sensitive dye (Di-4-ANEPPS) to predict adverse compound effects using hiPS-CMs and 20 cardioactive reference compounds. Fluorescence signals were digitized at 10kHz and the records subsequently analyzed off-line. Cells were exposed to 30min incubation to vehicle or compound (n=5/dose, 4 doses/compound) that were blinded to the investigating laboratory. Action potential parameters were measured, including rise time (T rise ) of the optical action potential duration (oAPD). Significant effects on oAPD were sensitively detected with 11 QT-prolonging drugs, while oAPD shortening was observed with I Ca -antagonists, I Kr -activator or ATP-sensitive K + channel (K ATP )-opener. Additionally, the assay detected varied effects induced by 6 different sodium channel blockers. The detection threshold for these drug effects was at or below the published values of free effective therapeutic plasma levels or effective concentrations by other studies. The results of this blinded study indicate that OAP is a sensitive method to accurately detect drug-induced effects (i.e., duration/QT-prolongation, shortening, beat rate, and incidence of early after depolarizations) in hiPS-CMs; therefore, this technique will potentially be useful in predicting drug-induced arrhythmogenic liabilities in early de-risking within the drug discovery phase. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Azithromycin/chloroquine combination does not increase cardiac instability despite an increase in monophasic action potential duration in the anesthetized guinea pig.

    PubMed

    Fossa, Anthony A; Wisialowski, Todd; Duncan, J Neil; Deng, Shibing; Dunne, Michael

    2007-11-01

    Prolongation of the electrocardiogram QT interval by some, but not all drugs, has been associated with increased incidence of sudden cardiac death. Current preclinical regulatory assays cannot discriminate the arrhythmia liability of these drugs. Consequently, many new medications that prolong the QT interval are not developed despite their potential therapeutic benefit. Alternans (action potential duration alternations) is a measure of cardiac instability in humans and animals associated with the onset of ventricular fibrillation. Due to potential arrhythmia risk from observed QT prolongation, alternans was assessed in the anesthetized guinea pig after azithromycin or chloroquine alone and after combination treatment at clinically relevant concentrations proposed for the management of malaria. Chloroquine alone, but not azithromycin, caused a profound increase in action potential duration but with only minimal effects on alternans (approximately 10 ms). Azithromycin alone and in combination with chloroquine showed no increase in alternans beyond vehicle baseline responses indicating no additional arrhythmia liability.

  2. Dirac-Born-Infeld actions and tachyon monopoles

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Calo, Vincenzo; Tallarita, Gianni; Thomas, Steven

    2010-04-15

    We investigate magnetic monopole solutions of the non-Abelian Dirac-Born-Infeld (DBI) action describing two coincident non-BPS D9-branes in flat space. Just as in the case of kink and vortex solitonic tachyon solutions of the full DBI non-BPS actions, as previously analyzed by Sen, these monopole configurations are singular in the first instance and require regularization. We discuss a suitable non-Abelian ansatz that describes a pointlike magnetic monopole and show it solves the equations of motion to leading order in the regularization parameter. Fluctuations are studied and shown to describe a codimension three BPS D6-brane, and a formula is derived for itsmore » tension.« less

  3. Redundant Array Configurations for 21 cm Cosmology

    NASA Astrophysics Data System (ADS)

    Dillon, Joshua S.; Parsons, Aaron R.

    2016-08-01

    Realizing the potential of 21 cm tomography to statistically probe the intergalactic medium before and during the Epoch of Reionization requires large telescopes and precise control of systematics. Next-generation telescopes are now being designed and built to meet these challenges, drawing lessons from first-generation experiments that showed the benefits of densely packed, highly redundant arrays—in which the same mode on the sky is sampled by many antenna pairs—for achieving high sensitivity, precise calibration, and robust foreground mitigation. In this work, we focus on the Hydrogen Epoch of Reionization Array (HERA) as an interferometer with a dense, redundant core designed following these lessons to be optimized for 21 cm cosmology. We show how modestly supplementing or modifying a compact design like HERA’s can still deliver high sensitivity while enhancing strategies for calibration and foreground mitigation. In particular, we compare the imaging capability of several array configurations, both instantaneously (to address instrumental and ionospheric effects) and with rotation synthesis (for foreground removal). We also examine the effects that configuration has on calibratability using instantaneous redundancy. We find that improved imaging with sub-aperture sampling via “off-grid” antennas and increased angular resolution via far-flung “outrigger” antennas is possible with a redundantly calibratable array configuration.

  4. REDUNDANT ARRAY CONFIGURATIONS FOR 21 cm COSMOLOGY

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Dillon, Joshua S.; Parsons, Aaron R., E-mail: jsdillon@berkeley.edu

    Realizing the potential of 21 cm tomography to statistically probe the intergalactic medium before and during the Epoch of Reionization requires large telescopes and precise control of systematics. Next-generation telescopes are now being designed and built to meet these challenges, drawing lessons from first-generation experiments that showed the benefits of densely packed, highly redundant arrays—in which the same mode on the sky is sampled by many antenna pairs—for achieving high sensitivity, precise calibration, and robust foreground mitigation. In this work, we focus on the Hydrogen Epoch of Reionization Array (HERA) as an interferometer with a dense, redundant core designed followingmore » these lessons to be optimized for 21 cm cosmology. We show how modestly supplementing or modifying a compact design like HERA’s can still deliver high sensitivity while enhancing strategies for calibration and foreground mitigation. In particular, we compare the imaging capability of several array configurations, both instantaneously (to address instrumental and ionospheric effects) and with rotation synthesis (for foreground removal). We also examine the effects that configuration has on calibratability using instantaneous redundancy. We find that improved imaging with sub-aperture sampling via “off-grid” antennas and increased angular resolution via far-flung “outrigger” antennas is possible with a redundantly calibratable array configuration.« less

  5. [Hardware Implementation of Numerical Simulation Function of Hodgkin-Huxley Model Neurons Action Potential Based on Field Programmable Gate Array].

    PubMed

    Wang, Jinlong; Lu, Mai; Hu, Yanwen; Chen, Xiaoqiang; Pan, Qiangqiang

    2015-12-01

    Neuron is the basic unit of the biological neural system. The Hodgkin-Huxley (HH) model is one of the most realistic neuron models on the electrophysiological characteristic description of neuron. Hardware implementation of neuron could provide new research ideas to clinical treatment of spinal cord injury, bionics and artificial intelligence. Based on the HH model neuron and the DSP Builder technology, in the present study, a single HH model neuron hardware implementation was completed in Field Programmable Gate Array (FPGA). The neuron implemented in FPGA was stimulated by different types of current, the action potential response characteristics were analyzed, and the correlation coefficient between numerical simulation result and hardware implementation result were calculated. The results showed that neuronal action potential response of FPGA was highly consistent with numerical simulation result. This work lays the foundation for hardware implementation of neural network.

  6. The Belem Framework for Action: Harnessing the Power and Potential of Adult Learning and Education for a Viable Future

    ERIC Educational Resources Information Center

    Adult Learning, 2012

    2012-01-01

    This article presents the Belem Framework for Action. This framework focuses on harnessing the power and potential of adult learning and education for a viable future. This framework begins with a preamble on adult education and towards lifelong learning.

  7. Analysis of transonic flow about lifting wing-body configurations

    NASA Technical Reports Server (NTRS)

    Barnwell, R. W.

    1975-01-01

    An analytical solution was obtained for the perturbation velocity potential for transonic flow about lifting wing-body configurations with order-one span-length ratios and small reduced-span-length ratios and equivalent-thickness-length ratios. The analysis is performed with the method of matched asymptotic expansions. The angles of attack which are considered are small but are large enough to insure that the effects of lift in the region far from the configuration are either dominant or comparable with the effects of thickness. The modification to the equivalence rule which accounts for these lift effects is determined. An analysis of transonic flow about lifting wings with large aspect ratios is also presented.

  8. Immunoglobulinfree light chains reduce in an antigen-specific manner the rate of rise of action potentials of mouse non-nociceptive dorsal root ganglion neurons.

    PubMed

    Rijnierse, Anneke; Kraneveld, Aletta D; Salemi, Arezo; Zwaneveld, Sandra; Goumans, Aleida P H; Rychter, Jakub W; Thio, Marco; Redegeld, Frank A; Westerink, Remco H S; Kroese, Alfons B A

    2013-11-15

    Plasma B cells secrete immunoglobulinfree light chains (IgLC) which by binding to mast cells can mediate hypersensitivity responses and are involved in several immunological disorders. To investigate the effects of antigen-specific IgLC activation, intracellular recordings were made from cultured murine dorsal root ganglion (DRG) neurons, which can specifically bind IgLC. The neurons were sensitized with IgLC for 90min and subsequently activated by application of the corresponding antigen (DNP-HSA). Antigen application induced a decrease in the rate of rise of the action potentials of non-nociceptive neurons (MANOVA, p=2.10(-6)), without affecting the resting membrane potential or firing threshold. The action potentials of the nociceptive neurons (p=0.57) and the electrical excitability of both types of neurons (p>0.35) were not affected. We conclude that IgLC can mediate antigen-specific responses by reducing the rate of rise of action potentials in non-nociceptive murine DRG neurons. We suggest that antigen-specific activation of IgLC-sensitized non-nociceptive DRG neurons may contribute to immunological hypersensitivity responses and neuroinflammation. © 2013.

  9. [The influence of various acoustic stimuli upon the cumulative action potential (SAP) of the auditory nerves in guinea pigs (author's transl)].

    PubMed

    Hofmann, G; Kraak, W

    1976-08-31

    The impact of various acoustic stimuli upon the cumulative action potential of the auditory nerves in guinea pigs is investigated by means of the averaging method. It was found that the potential amplitude within the measuring range increases with the logarithm of the rising sonic pressure velocity. Unlike the evoked response audiometry (ERA), this potential seems unsuitable for furnishing information of the frequency-dependent threshold course.

  10. Finite-action solutions of Yang-Mills equations on de Sitter dS4 and anti-de Sitter AdS4 spaces

    NASA Astrophysics Data System (ADS)

    Ivanova, Tatiana A.; Lechtenfeld, Olaf; Popov, Alexander D.

    2017-11-01

    We consider pure SU(2) Yang-Mills theory on four-dimensional de Sitter dS4 and anti-de Sitter AdS4 spaces and construct various solutions to the Yang-Mills equations. On de Sitter space we reduce the Yang-Mills equations via an SU(2)-equivariant ansatz to Newtonian mechanics of a particle moving in R^3 under the influence of a quartic potential. Then we describe magnetic and electric-magnetic solutions, both Abelian and non-Abelian, all having finite energy and finite action. A similar reduction on anti-de Sitter space also yields Yang-Mills solutions with finite energy and action. We propose a lower bound for the action on both backgrounds. Employing another metric on AdS4, the SU(2) Yang-Mills equations are reduced to an analytic continuation of the above particle mechanics from R^3 to R^{2,1} . We discuss analytical solutions to these equations, which produce infinite-action configurations. After a Euclidean continuation of dS4 and AdS4 we also present self-dual (instanton-type) Yang-Mills solutions on these backgrounds.

  11. Analysis of compound action potentials elicited with specific current stimulating pulses in an isolated rat sciatic nerve.

    PubMed

    Žužek, Monika C; Rozman, Janez; Pečlin, Polona; Vrecl, Milka; Frangež, Robert

    2017-02-01

    The ability to selectively stimulate Aα, Aβ-fibers and Aδ-fibers in an isolated rat sciatic nerve (SNR) was assessed. The stimulus used was a current, biphasic pulse with a quasitrapezoidal cathodic phase and rectangular anodic phase where parameters were systematically varied: intensity of the cathodic phase (ic); width of the cathodic phase (tc); width of the cathodic exponential decay (texp) and time constant of the exponential decay (τexp). A SNR was stimulated using a pair of hook electrodes while conduction velocity (CV) and compound action potentials (CAP) were measured at two sites along the SNR using another two pairs of electrodes. Results showed that the highest CAP1 (8.5-9 mV), shall be expected when parameters of the stimulus were within the following range: ic=3.8-4 mA, tc=350-400 μs and texp=330-440 μs. Results also showed that with ascending tc and texp, CV of the corresponding superficial region of the SNR was reduced in both, conduction velocity of CAP1 and conduction velocity of CAP2. It was concluded that action potentials (APs) were activated in the Aβ-fibers and Aδ-fibers along with a slight AP inhibition in the Aβ-fibers. The obtained results, could serve as a tool for developing multi-electrode systems that potentially enable fiber-type selective stimulation of nerve fibers.

  12. Impaired action potential initiation in GABAergic interneurons causes hyperexcitable networks in an epileptic mouse model carrying a human Na(V)1.1 mutation.

    PubMed

    Hedrich, Ulrike B S; Liautard, Camille; Kirschenbaum, Daniel; Pofahl, Martin; Lavigne, Jennifer; Liu, Yuanyuan; Theiss, Stephan; Slotta, Johannes; Escayg, Andrew; Dihné, Marcel; Beck, Heinz; Mantegazza, Massimo; Lerche, Holger

    2014-11-05

    Mutations in SCN1A and other ion channel genes can cause different epileptic phenotypes, but the precise mechanisms underlying the development of hyperexcitable networks are largely unknown. Here, we present a multisystem analysis of an SCN1A mouse model carrying the NaV1.1-R1648H mutation, which causes febrile seizures and epilepsy in humans. We found a ubiquitous hypoexcitability of interneurons in thalamus, cortex, and hippocampus, without detectable changes in excitatory neurons. Interestingly, somatic Na(+) channels in interneurons and persistent Na(+) currents were not significantly changed. Instead, the key mechanism of interneuron dysfunction was a deficit of action potential initiation at the axon initial segment that was identified by analyzing action potential firing. This deficit increased with the duration of firing periods, suggesting that increased slow inactivation, as recorded for recombinant mutated channels, could play an important role. The deficit in interneuron firing caused reduced action potential-driven inhibition of excitatory neurons as revealed by less frequent spontaneous but not miniature IPSCs. Multiple approaches indicated increased spontaneous thalamocortical and hippocampal network activity in mutant mice, as follows: (1) more synchronous and higher-frequency firing was recorded in primary neuronal cultures plated on multielectrode arrays; (2) thalamocortical slices examined by field potential recordings revealed spontaneous activities and pathological high-frequency oscillations; and (3) multineuron Ca(2+) imaging in hippocampal slices showed increased spontaneous neuronal activity. Thus, an interneuron-specific generalized defect in action potential initiation causes multisystem disinhibition and network hyperexcitability, which can well explain the occurrence of seizures in the studied mouse model and in patients carrying this mutation. Copyright © 2014 the authors 0270-6474/14/3414874-16$15.00/0.

  13. Lunar Surface Habitat Configuration Assessment: Methodology and Observations

    NASA Technical Reports Server (NTRS)

    Carpenter, Amanda

    2008-01-01

    The Lunar Habitat Configuration Assessment evaluated the major habitat approaches that were conceptually developed during the Lunar Architecture Team II Study. The objective of the configuration assessment was to identify desired features, operational considerations, and risks to derive habitat requirements. This assessment only considered operations pertaining to the lunar surface and did not consider all habitat conceptual designs developed. To examine multiple architectures, the Habitation Focus Element Team defined several adequate concepts which warranted the need for a method to assess the various configurations. The fundamental requirement designed into each concept included the functional and operational capability to support a crew of four on a six-month lunar surface mission; however, other conceptual aspects were diverse in comparison. The methodology utilized for this assessment consisted of defining figure of merits, providing relevant information, and establishing a scoring system. In summary, the assessment considered the geometric configuration of each concept to determine the complexity of unloading, handling, mobility, leveling, aligning, mating to other elements, and the accessibility to the lunar surface. In theory, the assessment was designed to derive habitat requirements, potential technology development needs and identify risks associated with living and working on the lunar surface. Although the results were more subjective opposed to objective, the assessment provided insightful observations for further assessments and trade studies of lunar surface habitats. This overall methodology and resulting observations will be describe in detail and illustrative examples will be discussed.

  14. From damage response to action potentials: early evolution of neural and contractile modules in stem eukaryotes.

    PubMed

    Brunet, Thibaut; Arendt, Detlev

    2016-01-05

    Eukaryotic cells convert external stimuli into membrane depolarization, which in turn triggers effector responses such as secretion and contraction. Here, we put forward an evolutionary hypothesis for the origin of the depolarization-contraction-secretion (DCS) coupling, the functional core of animal neuromuscular circuits. We propose that DCS coupling evolved in unicellular stem eukaryotes as part of an 'emergency response' to calcium influx upon membrane rupture. We detail how this initial response was subsequently modified into an ancient mechanosensory-effector arc, present in the last eukaryotic common ancestor, which enabled contractile amoeboid movement that is widespread in extant eukaryotes. Elaborating on calcium-triggered membrane depolarization, we reason that the first action potentials evolved alongside the membrane of sensory-motile cilia, with the first voltage-sensitive sodium/calcium channels (Nav/Cav) enabling a fast and coordinated response of the entire cilium to mechanosensory stimuli. From the cilium, action potentials then spread across the entire cell, enabling global cellular responses such as concerted contraction in several independent eukaryote lineages. In animals, this process led to the invention of mechanosensory contractile cells. These gave rise to mechanosensory receptor cells, neurons and muscle cells by division of labour and can be regarded as the founder cell type of the nervous system. © 2015 The Authors.

  15. From damage response to action potentials: early evolution of neural and contractile modules in stem eukaryotes

    PubMed Central

    Brunet, Thibaut; Arendt, Detlev

    2016-01-01

    Eukaryotic cells convert external stimuli into membrane depolarization, which in turn triggers effector responses such as secretion and contraction. Here, we put forward an evolutionary hypothesis for the origin of the depolarization–contraction–secretion (DCS) coupling, the functional core of animal neuromuscular circuits. We propose that DCS coupling evolved in unicellular stem eukaryotes as part of an ‘emergency response’ to calcium influx upon membrane rupture. We detail how this initial response was subsequently modified into an ancient mechanosensory–effector arc, present in the last eukaryotic common ancestor, which enabled contractile amoeboid movement that is widespread in extant eukaryotes. Elaborating on calcium-triggered membrane depolarization, we reason that the first action potentials evolved alongside the membrane of sensory-motile cilia, with the first voltage-sensitive sodium/calcium channels (Nav/Cav) enabling a fast and coordinated response of the entire cilium to mechanosensory stimuli. From the cilium, action potentials then spread across the entire cell, enabling global cellular responses such as concerted contraction in several independent eukaryote lineages. In animals, this process led to the invention of mechanosensory contractile cells. These gave rise to mechanosensory receptor cells, neurons and muscle cells by division of labour and can be regarded as the founder cell type of the nervous system. PMID:26598726

  16. The Impact of Continental Configuration on Global Response to Large Igneous Province Eruptions

    NASA Astrophysics Data System (ADS)

    Stellmann, J.; West, A. J.; Ridgwell, A.; Becker, T. W.

    2017-12-01

    The impact of Large Igneous Province eruptions as recorded in the geologic record varies widely; some eruptions cause global warming, large scale ocean acidification and anoxia and mass extinctions while others cause some or none of these phenomena. There are several potential factors which may determine the global response to a Large Igneous Province eruption; here we consider continental configuration. The arrangement of continents controls the extent of shallow seas, ocean circulation and planetary albedo; all factors which impact global climate and its response to sudden changes in greenhouse gas concentrations. To assess the potential impact of continental configuration, a suite of simulated eruptions was carried out using the cGENIE Earth system model in two end-member continental configurations: the end-Permian supercontinent and the modern. Eruptions simulated are comparable to an individual pulse of a Large Igneous Province eruption with total CO2 emissions of 1,000 or 10,000 GtC erupted over 1,000 or 10,000 years, spanning eruptions rates of .1-10 GtC/yr. Global response is characterized by measuring the magnitude and duration of changes to atmospheric concentration of CO2, saturation state of calcite and ocean oxygen levels. Preliminary model results show that end-Permian continental configuration and conditions (radiative balance, ocean chemistry) lead to smaller magnitude and shorter duration changes in atmospheric pCO2 and ocean saturation state of calcite following the simulated eruption than the modern configuration.

  17. Correlates of a single cortical action potential in the epidural EEG

    PubMed Central

    Teleńczuk, Bartosz; Baker, Stuart N; Kempter, Richard; Curio, Gabriel

    2015-01-01

    To identify the correlates of a single cortical action potential in surface EEG, we recorded simultaneously epidural EEG and single-unit activity in the primary somatosensory cortex of awake macaque monkeys. By averaging over EEG segments coincident with more than hundred thousand single spikes, we found short-lived (≈ 0.5 ms) triphasic EEG deflections dominated by high-frequency components > 800 Hz. The peak-to-peak amplitude of the grand-averaged spike correlate was 80 nV, which matched theoretical predictions, while single-neuron amplitudes ranged from 12 to 966 nV. Combining these estimates with post-stimulus-time histograms of single-unit responses to median-nerve stimulation allowed us to predict the shape of the evoked epidural EEG response and to estimate the number of contributing neurons. These findings establish spiking activity of cortical neurons as a primary building block of high-frequency epidural EEG, which thus can serve as a quantitative macroscopic marker of neuronal spikes. PMID:25554430

  18. Upregulation of K(2P)3.1 K+ Current Causes Action Potential Shortening in Patients With Chronic Atrial Fibrillation.

    PubMed

    Schmidt, Constanze; Wiedmann, Felix; Voigt, Niels; Zhou, Xiao-Bo; Heijman, Jordi; Lang, Siegfried; Albert, Virginia; Kallenberger, Stefan; Ruhparwar, Arjang; Szabó, Gábor; Kallenbach, Klaus; Karck, Matthias; Borggrefe, Martin; Biliczki, Peter; Ehrlich, Joachim R; Baczkó, István; Lugenbiel, Patrick; Schweizer, Patrick A; Donner, Birgit C; Katus, Hugo A; Dobrev, Dobromir; Thomas, Dierk

    2015-07-14

    Antiarrhythmic management of atrial fibrillation (AF) remains a major clinical challenge. Mechanism-based approaches to AF therapy are sought to increase effectiveness and to provide individualized patient care. K(2P)3.1 (TASK-1 [tandem of P domains in a weak inward-rectifying K+ channel-related acid-sensitive K+ channel-1]) 2-pore-domain K+ (K(2P)) channels have been implicated in action potential regulation in animal models. However, their role in the pathophysiology and treatment of paroxysmal and chronic patients with AF is unknown. Right and left atrial tissue was obtained from patients with paroxysmal or chronic AF and from control subjects in sinus rhythm. Ion channel expression was analyzed by quantitative real-time polymerase chain reaction and Western blot. Membrane currents and action potentials were recorded using voltage- and current-clamp techniques. K(2P)3.1 subunits exhibited predominantly atrial expression, and atrial K(2P)3.1 transcript levels were highest among functional K(2P) channels. K(2P)3.1 mRNA and protein levels were increased in chronic AF. Enhancement of corresponding currents in the right atrium resulted in shortened action potential duration at 90% of repolarization (APD90) compared with patients in sinus rhythm. In contrast, K(2P)3.1 expression was not significantly affected in subjects with paroxysmal AF. Pharmacological K(2P)3.1 inhibition prolonged APD90 in atrial myocytes from patients with chronic AF to values observed among control subjects in sinus rhythm. Enhancement of atrium-selective K(2P)3.1 currents contributes to APD shortening in patients with chronic AF, and K(2P)3.1 channel inhibition reverses AF-related APD shortening. These results highlight the potential of K(2P)3.1 as a novel drug target for mechanism-based AF therapy. © 2015 American Heart Association, Inc.

  19. Intermolecular configurations dominated by quadrupole-quadrupole electrostatic interactions: explicit correlation treatment of the five-dimensional potential energy surface and infrared spectra for the CO-N2 complex.

    PubMed

    Liu, Jing-Min; Zhai, Yu; Zhang, Xiao-Long; Li, Hui

    2018-01-17

    A thorough understanding of the intermolecular configurations of van der Waals complexes is a great challenge due to their weak interactions, floppiness and anharmonic nature. Although high-resolution microwave or infrared spectroscopy provides one of the most direct and precise pieces of experimental evidence, the origin and key role in determining such intermolecular configurations of a van der Waals system strongly depend on its highly accurate potential energy surface (PES) and a detailed analysis of its ro-vibrational wavefunctions. Here, a new five-dimensional potential energy surface for the van der Waals complex of CO-N 2 which explicitly incorporates the dependence on the stretch coordinate of the CO monomer is generated using the explicitly correlated couple cluster (CCSD(T)-F12) method in conjunction with a large basis set. Analytic four-dimensional PESs are obtained by the least-squares fitting of vibrationally averaged interaction energies for v = 0 and v = 1 to the Morse/Long-Range potential mode (V MLR ). These fits to 7966 points have root-mean-square deviations (RMSD) of 0.131 cm -1 and 0.129 cm -1 for v = 0 and v = 1, respectively, with only 315 parameters. Energy decomposition analysis is carried out, and it reveals that the dominant factor in controlling intermolecular configurations is quadrupole-quadrupole electrostatic interactions. Moreover, the rovibrational levels and wave functions are obtained for the first time. The predicted infrared transitions and intensities for the ortho-N 2 -CO complex as well as the calculated energy levels for para-N 2 -CO are in good agreement with the available experimental data with RMSD discrepancies smaller than 0.068 cm -1 . The calculated infrared band origin shift associated with the fundamental band frequency of CO is -0.721 cm -1 for ortho-N 2 -CO which is in excellent agreement with the experimental value of -0.739 cm -1 . The agreement with experimental values validates the high quality of the PESs

  20. Non-orthogonal internally contracted multi-configurational perturbation theory (NICPT): Dynamic electron correlation for large, compact active spaces

    NASA Astrophysics Data System (ADS)

    Kähler, Sven; Olsen, Jeppe

    2017-11-01

    A computational method is presented for systems that require high-level treatments of static and dynamic electron correlation but cannot be treated using conventional complete active space self-consistent field-based methods due to the required size of the active space. Our method introduces an efficient algorithm for perturbative dynamic correlation corrections for compact non-orthogonal MCSCF calculations. In the algorithm, biorthonormal expansions of orbitals and CI-wave functions are used to reduce the scaling of the performance determining step from quadratic to linear in the number of configurations. We describe a hierarchy of configuration spaces that can be chosen for the active space. Potential curves for the nitrogen molecule and the chromium dimer are compared for different configuration spaces. Already the most compact spaces yield qualitatively correct potentials that with increasing size of configuration spaces systematically approach complete active space results.

  1. Differential Regulation of Action Potential Shape and Burst-Frequency Firing by BK and Kv2 Channels in Substantia Nigra Dopaminergic Neurons

    PubMed Central

    Kimm, Tilia; Khaliq, Zayd M.

    2015-01-01

    Little is known about the voltage-dependent potassium currents underlying spike repolarization in midbrain dopaminergic neurons. Studying mouse substantia nigra pars compacta dopaminergic neurons both in brain slice and after acute dissociation, we found that BK calcium-activated potassium channels and Kv2 channels both make major contributions to the depolarization-activated potassium current. Inhibiting Kv2 or BK channels had very different effects on spike shape and evoked firing. Inhibiting Kv2 channels increased spike width and decreased the afterhyperpolarization, as expected for loss of an action potential-activated potassium conductance. BK inhibition also increased spike width but paradoxically increased the afterhyperpolarization. Kv2 channel inhibition steeply increased the slope of the frequency–current (f–I) relationship, whereas BK channel inhibition had little effect on the f–I slope or decreased it, sometimes resulting in slowed firing. Action potential clamp experiments showed that both BK and Kv2 current flow during spike repolarization but with very different kinetics, with Kv2 current activating later and deactivating more slowly. Further experiments revealed that inhibiting either BK or Kv2 alone leads to recruitment of additional current through the other channel type during the action potential as a consequence of changes in spike shape. Enhancement of slowly deactivating Kv2 current can account for the increased afterhyperpolarization produced by BK inhibition and likely underlies the very different effects on the f–I relationship. The cross-regulation of BK and Kv2 activation illustrates that the functional role of a channel cannot be defined in isolation but depends critically on the context of the other conductances in the cell. SIGNIFICANCE STATEMENT This work shows that BK calcium-activated potassium channels and Kv2 voltage-activated potassium channels both regulate action potentials in dopamine neurons of the substantia nigra

  2. Differential Regulation of Action Potential Shape and Burst-Frequency Firing by BK and Kv2 Channels in Substantia Nigra Dopaminergic Neurons.

    PubMed

    Kimm, Tilia; Khaliq, Zayd M; Bean, Bruce P

    2015-12-16

    Little is known about the voltage-dependent potassium currents underlying spike repolarization in midbrain dopaminergic neurons. Studying mouse substantia nigra pars compacta dopaminergic neurons both in brain slice and after acute dissociation, we found that BK calcium-activated potassium channels and Kv2 channels both make major contributions to the depolarization-activated potassium current. Inhibiting Kv2 or BK channels had very different effects on spike shape and evoked firing. Inhibiting Kv2 channels increased spike width and decreased the afterhyperpolarization, as expected for loss of an action potential-activated potassium conductance. BK inhibition also increased spike width but paradoxically increased the afterhyperpolarization. Kv2 channel inhibition steeply increased the slope of the frequency-current (f-I) relationship, whereas BK channel inhibition had little effect on the f-I slope or decreased it, sometimes resulting in slowed firing. Action potential clamp experiments showed that both BK and Kv2 current flow during spike repolarization but with very different kinetics, with Kv2 current activating later and deactivating more slowly. Further experiments revealed that inhibiting either BK or Kv2 alone leads to recruitment of additional current through the other channel type during the action potential as a consequence of changes in spike shape. Enhancement of slowly deactivating Kv2 current can account for the increased afterhyperpolarization produced by BK inhibition and likely underlies the very different effects on the f-I relationship. The cross-regulation of BK and Kv2 activation illustrates that the functional role of a channel cannot be defined in isolation but depends critically on the context of the other conductances in the cell. This work shows that BK calcium-activated potassium channels and Kv2 voltage-activated potassium channels both regulate action potentials in dopamine neurons of the substantia nigra pars compacta. Although both

  3. An Implementation of the Action Space Concept in Behavioral Analysis.

    ERIC Educational Resources Information Center

    Higgs, Gary K.

    The Contact Action Space (CAS) of an individual, or group of individuals, has a significant impact on the location of activities and the organization of the use of space. Beginning with the most basic components of a CAS, the individual behavior pattern element is developed, and operational variations affecting alignment and configuration are…

  4. Modes of therapeutic action.

    PubMed

    Jones, E E

    1997-12-01

    The dialectic in psychoanalysis between theories about the mutative effects of interpretation and psychological knowledge and those concerning the effects of interpersonal interaction constitutes an important tension for approaches to psychoanalytic technique. This essay briefly summarises the thinking around these alternative conceptualisations of therapeutic action, and introduces a new empirically derived model, that of 'repetitive interaction structure', which attempts to bridge therapeutic action by insight and by relationship. Interaction structure is a way of formulating those aspects of the analytic process that have come to be termed intersubjectivity, transference-countertransference enactments and role responsiveness. The concept operationalises important aspects of interpersonal interaction, and can help specify the two-person patterns that emerge in an analysis. Patient and analyst interact in repetitive ways; these patterns of interaction, which are slow to change, probably reflect the psychological structure of both patient and analyst, whether psychic structure is conceptualised in terms of object-representations or compromise formations and impulse-defence configurations. Therapeutic action is located in the experience, recognition and understanding by patient and analyst of these repetitive interactions. Interaction structures stress the importance of the intrapsychic as a basis for what becomes manifest in the interactive field. Clinical illustrations from a psychoanalysis are provided, and research on repetitive interaction structures is described.

  5. Parametric analysis of ATT configurations.

    NASA Technical Reports Server (NTRS)

    Lange, R. H.

    1972-01-01

    This paper describes the results of a Lockheed parametric analysis of the performance, environmental factors, and economics of an advanced commercial transport envisioned for operation in the post-1985 time period. The design parameters investigated include cruise speeds from Mach 0.85 to Mach 1.0, passenger capacities from 200 to 500, ranges of 2800 to 5500 nautical miles, and noise level criteria. NASA high performance configurations and alternate configurations are operated over domestic and international route structures. Indirect and direct costs and return on investment are determined for approximately 40 candidate aircraft configurations. The candidate configurations are input to an aircraft sizing and performance program which includes a subroutine for noise criteria. Comparisons are made between preferred configurations on the basis of maximum return on investment as a function of payload, range, and design cruise speed.

  6. Comment on "Penetration of Action Potentials During Collision in the Median and Lateral Giant Axons of Invertebrates"

    NASA Astrophysics Data System (ADS)

    Berg, Rune W.; Stauning, Marius Tving; Sørensen, Jakob Balslev; Jahnsen, Henrik

    2017-04-01

    The action potential (AP) is an electrical impulse elicited by depolarization of the neuronal membrane from the resting membrane potential (around -70 mV ). It propagates along the axon, allowing for rapid and distant communication. Recently, it was claimed that two APs traveling in opposite direction will pass unhindered through each other (penetrate) upon collision [Gonzalez-Perez et al.Phys. Rev. X 4, 031047 (2014), 10.1103/PhysRevX.4.031047]. We tested this claim under carefully controlled conditions and found that we cannot reproduce penetration. Instead, APs consistently annihilated upon collision. This is consistent with a vast body of literature.

  7. Viscous Design of TCA Configuration

    NASA Technical Reports Server (NTRS)

    Krist, Steven E.; Bauer, Steven X. S.; Campbell, Richard L.

    1999-01-01

    The goal in this effort is to redesign the baseline TCA configuration for improved performance at both supersonic and transonic cruise. Viscous analyses are conducted with OVERFLOW, a Navier-Stokes code for overset grids, using PEGSUS to compute the interpolations between overset grids. Viscous designs are conducted with OVERDISC, a script which couples OVERFLOW with the Constrained Direct Iterative Surface Curvature (CDISC) inverse design method. The successful execution of any computational fluid dynamics (CFD) based aerodynamic design method for complex configurations requires an efficient method for regenerating the computational grids to account for modifications to the configuration shape. The first section of this presentation deals with the automated regridding procedure used to generate overset grids for the fuselage/wing/diverter/nacelle configurations analysed in this effort. The second section outlines the procedures utilized to conduct OVERDISC inverse designs. The third section briefly covers the work conducted by Dick Campbell, in which a dual-point design at Mach 2.4 and 0.9 was attempted using OVERDISC; the initial configuration from which this design effort was started is an early version of the optimized shape for the TCA configuration developed by the Boeing Commercial Airplane Group (BCAG), which eventually evolved into the NCV design. The final section presents results from application of the Natural Flow Wing design philosophy to the TCA configuration.

  8. 76 FR 40811 - Maneb; Tolerance Actions

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-12

    ...; Tolerance Actions AGENCY: Environmental Protection Agency (EPA). ACTION: Final rule. SUMMARY: EPA is... established a docket for this action under docket identification (ID) number EPA-HQ-OPP-2010-0327. All... . SUPPLEMENTARY INFORMATION: I. General Information A. Does this action apply to me? You may be potentially...

  9. The Potential Therapeutic Agent Mepacrine Protects Caco-2 Cells against Clostridium perfringens Enterotoxin Action.

    PubMed

    Freedman, John C; Hendricks, Matthew R; McClane, Bruce A

    2017-01-01

    Clostridium perfringens enterotoxin (CPE) causes the diarrhea associated with a common bacterial food poisoning and many antibiotic-associated diarrhea cases. The severity of some CPE-mediated disease cases warrants the development of potential therapeutics. A previous study showed that the presence of mepacrine inhibited CPE-induced electrophysiology effects in artificial lipid bilayers lacking CPE receptors. However, that study did not assess whether mepacrine inactivates CPE or, instead, inhibits a step in CPE action. Furthermore, CPE action in host cells is complex, involving the toxin binding to receptors, receptor-bound CPE oligomerizing into a prepore on the membrane surface, and β-hairpins in the CPE prepore inserting into the membrane to form a pore that induces cell death. Therefore, the current study evaluated the ability of mepacrine to protect cells from CPE. This drug was found to reduce CPE-induced cytotoxicity in Caco-2 cells. This protection did not involve mepacrine inactivation of CPE, indicating that mepacrine affects one or more steps in CPE action. Western blotting then demonstrated that mepacrine decreases CPE pore levels in Caco-2 cells. This mepacrine-induced reduction in CPE pore levels did not involve CPE binding inhibition but rather an increase in CPE monomer dissociation due to mepacrine interactions with Caco-2 membranes. In addition, mepacrine was also shown to inhibit CPE pores when already present in Caco-2 cells. These in vitro studies, which identified two mepacrine-sensitive steps in CPE-induced cytotoxicity, add support to further testing of the therapeutic potential of mepacrine against CPE-mediated disease. IMPORTANCE Clostridium perfringens enterotoxin (CPE) causes the gastrointestinal (GI) symptoms of a common bacterial food poisoning and several nonfoodborne human GI diseases. A previous study showed that, via an undetermined mechanism, the presence of mepacrine blocks CPE-induced electrophysiologic activity in artificial

  10. TWRS Configuration management program plan

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Vann, J.M.

    The TWRS Configuration Management Program Plan (CMPP) integrates technical and administrative controls to establish and maintain consistency among requirements, product configuration, and product information for TWRS products during all life cycle phases. This CMPP will be used by TWRS management and configuration management personnel to establish and manage the technical and integrated baselines and controls and status changes to those baselines.

  11. Anaesthetics stop diverse plant organ movements, affect endocytic vesicle recycling and ROS homeostasis, and block action potentials in Venus flytraps.

    PubMed

    Yokawa, K; Kagenishi, T; Pavlovic, A; Gall, S; Weiland, M; Mancuso, S; Baluška, F

    2017-12-11

    Anaesthesia for medical purposes was introduced in the 19th century. However, the physiological mode of anaesthetic drug actions on the nervous system remains unclear. One of the remaining questions is how these different compounds, with no structural similarities and even chemically inert elements such as the noble gas xenon, act as anaesthetic agents inducing loss of consciousness. The main goal here was to determine if anaesthetics affect the same or similar processes in plants as in animals and humans. A single-lens reflex camera was used to follow organ movements in plants before, during and after recovery from exposure to diverse anaesthetics. Confocal microscopy was used to analyse endocytic vesicle trafficking. Electrical signals were recorded using a surface AgCl electrode. Mimosa leaves, pea tendrils, Venus flytraps and sundew traps all lost both their autonomous and touch-induced movements after exposure to anaesthetics. In Venus flytrap, this was shown to be due to the loss of action potentials under diethyl ether anaesthesia. The same concentration of diethyl ether immobilized pea tendrils. Anaesthetics also impeded seed germination and chlorophyll accumulation in cress seedlings. Endocytic vesicle recycling and reactive oxygen species (ROS) balance, as observed in intact Arabidopsis root apex cells, were also affected by all anaesthetics tested. Plants are sensitive to several anaesthetics that have no structural similarities. As in animals and humans, anaesthetics used at appropriate concentrations block action potentials and immobilize organs via effects on action potentials, endocytic vesicle recycling and ROS homeostasis. Plants emerge as ideal model objects to study general questions related to anaesthesia, as well as to serve as a suitable test system for human anaesthesia. © The Authors 2017. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  12. Enhancing Postgraduate Learning and Development: A Participatory Action Learning and Action Research Approach through Conferences

    ERIC Educational Resources Information Center

    Wood, Lesley; Louw, Ina; Zuber-Skerritt, Ortrun

    2017-01-01

    As supervisors who advocate the transformational potential of research both to generate theory and practical and emancipatory outcomes, we practice participatory action learning and action research (PALAR). This paper offers an illustrative case of how supervision practices based on action learning can foster emancipatory and lifelong learning…

  13. [Phenibut potentiation of the therapeutic action of antiparkinson agents].

    PubMed

    Gol'dblat, Iu V; Lapin, I P

    1986-01-01

    It was observed in experiments on mice that the central action of phenibut (beta-phenyl-gamma-aminobutyric acid) diminished after destruction of brain dopaminergic neurons by 6-hydroxydopamine and after pretreatment with the dopamine receptor blocker haloperidol which suggests the dopaminergic component in the action of phenibut. In 13 of 16 patients receiving long-term treatment with antiparkinsonic drugs, addition of phenibut (0.25 g thrice daily for 10 days) resulted in marked clinical improvement with a significant increase of motor activity, as well as diminution of both rigidity and tremor. Follow-up showed a significant lowering of muscle tone of rigid muscles, augmentation of their strength and amplitude of movements. In 8 patients receiving phenibut without antiparkinsonic drugs the results were negligible.

  14. Enhancing Graphene Capacitance by Nitrogen: Effects of Doping Configuration and Concentration

    DOE PAGES

    Zhan, Cheng; Cummings, Peter; Jiang, De-en

    2016-01-08

    Recent experiments have shown that nitrogen doping enhances capacitance in carbon electrode supercapacitors. However, a detailed study of the effect of N-doping on capacitance is still lacking. In this paper, we study the doping concentration and the configuration effect on the electric double-layer (EDL) capacitance, quantum capacitance, and total capacitance. It is found that pyridinic and graphitic nitrogens can increase the total capacitance by increasing quantum capacitance, but pyrrolic configuration limits the total capacitance due to its much lower quantum capacitance than the other two configurations. We also find that, unlike the graphitic and pyridinic nitrogens, the pyrrolic configuration's quantummore » capacitance does not depend on the nitrogen concentration, which may explain why some capacitance versus voltage measurements of N-doped graphene exhibit a V-shaped curve similar to that of undoped graphene. Our investigation provides a deeper understanding of the capacitance enhancement of the N-doping effect in carbon electrodes and suggests a potentially effective way to optimize the capacitance by controlling the type of N-doping.« less

  15. Continuous Security and Configuration Monitoring of HPC Clusters

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Garcia-Lomeli, H. D.; Bertsch, A. D.; Fox, D. M.

    Continuous security and configuration monitoring of information systems has been a time consuming and laborious task for system administrators at the High Performance Computing (HPC) center. Prior to this project, system administrators had to manually check the settings of thousands of nodes, which required a significant number of hours rendering the old process ineffective and inefficient. This paper explains the application of Splunk Enterprise, a software agent, and a reporting tool in the development of a user application interface to track and report on critical system updates and security compliance status of HPC Clusters. In conjunction with other configuration managementmore » systems, the reporting tool is to provide continuous situational awareness to system administrators of the compliance state of information systems. Our approach consisted of the development, testing, and deployment of an agent to collect any arbitrary information across a massively distributed computing center, and organize that information into a human-readable format. Using Splunk Enterprise, this raw data was then gathered into a central repository and indexed for search, analysis, and correlation. Following acquisition and accumulation, the reporting tool generated and presented actionable information by filtering the data according to command line parameters passed at run time. Preliminary data showed results for over six thousand nodes. Further research and expansion of this tool could lead to the development of a series of agents to gather and report critical system parameters. However, in order to make use of the flexibility and resourcefulness of the reporting tool the agent must conform to specifications set forth in this paper. This project has simplified the way system administrators gather, analyze, and report on the configuration and security state of HPC clusters, maintaining ongoing situational awareness. Rather than querying each cluster independently, compliance

  16. Human neural tuning estimated from compound action potentials in normal hearing human volunteers

    NASA Astrophysics Data System (ADS)

    Verschooten, Eric; Desloovere, Christian; Joris, Philip X.

    2015-12-01

    The sharpness of cochlear frequency tuning in humans is debated. Evoked otoacoustic emissions and psychophysical measurements suggest sharper tuning in humans than in laboratory animals [15], but this is disputed based on comparisons of behavioral and electrophysiological measurements across species [14]. Here we used evoked mass potentials to electrophysiologically quantify tuning (Q10) in humans. We combined a notched noise forward masking paradigm [9] with the recording of trans tympanic compound action potentials (CAP) from masked probe tones in awake human and anesthetized monkey (Macaca mulatta). We compare our results to data obtained with the same paradigm in cat and chinchilla [16], and find that CAP-Q10values in human are ˜1.6x higher than in cat and chinchilla and ˜1.3x higher than in monkey. To estimate frequency tuning of single auditory nerve fibers (ANFs) in humans, we derive conversion functions from ANFs in cat, chinchilla, and monkey and apply these to the human CAP measurements. The data suggest that sharp cochlear tuning is a feature of old-world primates.

  17. A novel BCI based on ERP components sensitive to configural processing of human faces.

    PubMed

    Zhang, Yu; Zhao, Qibin; Jin, Jing; Wang, Xingyu; Cichocki, Andrzej

    2012-04-01

    This study introduces a novel brain-computer interface (BCI) based on an oddball paradigm using stimuli of facial images with loss of configural face information (e.g., inversion of face). To the best of our knowledge, till now the configural processing of human faces has not been applied to BCI but widely studied in cognitive neuroscience research. Our experiments confirm that the face-sensitive event-related potential (ERP) components N170 and vertex positive potential (VPP) have reflected early structural encoding of faces and can be modulated by the configural processing of faces. With the proposed novel paradigm, we investigate the effects of ERP components N170, VPP and P300 on target detection for BCI. An eight-class BCI platform is developed to analyze ERPs and evaluate the target detection performance using linear discriminant analysis without complicated feature extraction processing. The online classification accuracy of 88.7% and information transfer rate of 38.7 bits min(-1) using stimuli of inverted faces with only single trial suggest that the proposed paradigm based on the configural processing of faces is very promising for visual stimuli-driven BCI applications.

  18. A novel BCI based on ERP components sensitive to configural processing of human faces

    NASA Astrophysics Data System (ADS)

    Zhang, Yu; Zhao, Qibin; Jing, Jin; Wang, Xingyu; Cichocki, Andrzej

    2012-04-01

    This study introduces a novel brain-computer interface (BCI) based on an oddball paradigm using stimuli of facial images with loss of configural face information (e.g., inversion of face). To the best of our knowledge, till now the configural processing of human faces has not been applied to BCI but widely studied in cognitive neuroscience research. Our experiments confirm that the face-sensitive event-related potential (ERP) components N170 and vertex positive potential (VPP) have reflected early structural encoding of faces and can be modulated by the configural processing of faces. With the proposed novel paradigm, we investigate the effects of ERP components N170, VPP and P300 on target detection for BCI. An eight-class BCI platform is developed to analyze ERPs and evaluate the target detection performance using linear discriminant analysis without complicated feature extraction processing. The online classification accuracy of 88.7% and information transfer rate of 38.7 bits min-1 using stimuli of inverted faces with only single trial suggest that the proposed paradigm based on the configural processing of faces is very promising for visual stimuli-driven BCI applications.

  19. Facilitating Youth to Take Sustainability Actions: The Potential of Peer Education

    ERIC Educational Resources Information Center

    de Vreede, Catherine; Warner, Alan; Pitter, Robert

    2014-01-01

    Peer education is an understudied yet valuable strategy for sustainability educators in shifting youth to take action for sustainability. This case study conceptualizes the change process in facilitating youth to take sustainability actions, and explores the benefits, dynamics, and challenges of peer education as a strategy in facilitating change.…

  20. Facilitation and refractoriness of the electrically evoked compound action potential.

    PubMed

    Hey, Matthias; Müller-Deile, Joachim; Hessel, Horst; Killian, Matthijs

    2017-11-01

    In this study we aim to resolve the contributions of facilitation and refractoriness at very short pulse intervals. Measurements of the refractory properties of the electrically evoked compound action potential (ECAP) of the auditory nerve in cochlear implant (CI) users at inter pulse intervals below 300 μs are influenced by facilitation and recovery effects. ECAPs were recorded using masker pulses with a wide range of current levels relative to the probe pulse levels, for three suprathreshold probe levels and pulse intervals from 13 to 200 μs. Evoked potentials were measured for 21 CI patients by using the masked response extraction artifact cancellation procedure. During analysis of the measurements the stimulation current was not used as absolute value, but in relation to the patient's individual ECAP threshold. This enabled a more general approach to describe facilitation as a probe level independent effect. Maximum facilitation was found for all tested inter pulse intervals at masker levels near patient's individual ECAP threshold, independent from probe level. For short inter pulse intervals an increased N 1 P 1 amplitude was measured for subthreshold masker levels down to 120 CL below patient's individual ECAP threshold in contrast to the recreated state. ECAPs recorded with inter pulse intervals up to 200 μs are influenced by facilitation and recovery. Facilitation effects are most pronounced for masker levels at or below ECAP threshold, while recovery effects increase with higher masker levels above ECAP threshold. The local maximum of the ECAP amplitude for masker levels around ECAP threshold can be explained by the mutual influence of maximum facilitation and minimal refractoriness. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  1. Biomechanical and performance implications of weapon design: comparison of bullpup and conventional configurations.

    PubMed

    Stone, Richard T; Moeller, Brandon F; Mayer, Robert R; Rosenquist, Bryce; Van Ryswyk, Darin; Eichorn, Drew

    2014-06-01

    Shooter accuracy and stability were monitored while firing two bullpup and two conventional configuration rifles of the same caliber in order to determine if one style of weapon results in superior performance. Considerable debate exists among police and military professionals regarding the differences between conventional configuration weapons, where the magazine and action are located ahead of the trigger, and bullpup configuration, where they are located behind the trigger (closer to the user). To date, no published research has attempted to evaluate this question from a physical ergonomics standpoint, and the knowledge that one style might improve stability or result in superior performance is of interest to countless military, law enforcement, and industry experts. A live-fire evaluation of both weapon styles was performed using a total of 48 participants. Shooting accuracy and fluctuations in biomechanical stability (center of pressure) were monitored while subjects used the weapons to perform standard drills. The bullpup weapon designs were found to provide a significant advantage in accuracy and shooter stability, while subjects showed considerable preference toward the conventional weapons. Although many mechanical and maintenance issues must be considered before committing to a bullpup or conventional weapon system, it is clear in terms of basic human stability that the bullpup is the more advantageous configuration. Results can be used by competitive shooter, military, law enforcement, and industry experts while outfitting personnel with a weapon system that leads to superior performance.

  2. Acute Effect of Pore-Forming Clostridium perfringens ε-Toxin on Compound Action Potentials of Optic Nerve of Mouse.

    PubMed

    Cases, Mercè; Llobet, Artur; Terni, Beatrice; Gómez de Aranda, Inmaculada; Blanch, Marta; Doohan, Briain; Revill, Alexander; Brown, Angus M; Blasi, Juan; Solsona, Carles

    2017-01-01

    ε-Toxin is a pore forming toxin produced by Clostridium perfringens types B and D. It is synthesized as a less active prototoxin form that becomes fully active upon proteolytic activation. The toxin produces highly lethal enterotoxaemia in ruminants, has the ability to cross the blood-brain barrier (BBB) and specifically binds to myelinated fibers. We discovered that the toxin induced a release of ATP from isolated mice optic nerves, which are composed of myelinated fibers that are extended from the central nervous system. We also investigated the effect of the toxin on compound action potentials (CAPs) in isolated mice optic nerves. When nerves were stimulated at 100 Hz during 200 ms, the decrease of the amplitude and the area of the CAPs was attenuated in the presence of ε-toxin. The computational modelling of myelinated fibers of mouse optic nerve revealed that the experimental results can be mimicked by an increase of the conductance of myelin and agrees with the pore forming activity of the toxin which binds to myelin and could drill it by making pores. The intimate ultrastructure of myelin was not modified during the periods of time investigated. In summary, the acute action of the toxin produces a subtle functional impact on the propagation of the nerve action potential in myelinated fibers of the central nervous system with an eventual desynchronization of the information. These results may agree with the hypothesis that the toxin could be an environmental trigger of multiple sclerosis (MS).

  3. A multiscale approach to modelling electrochemical processes occurring across the cell membrane with application to transmission of action potentials.

    PubMed

    Richardson, G

    2009-09-01

    By application of matched asymptotic expansions, a simplified partial differential equation (PDE) model for the dynamic electrochemical processes occurring in the vicinity of a membrane, as ions selectively permeate across it, is formally derived from the Poisson-Nernst-Planck equations of electrochemistry. It is demonstrated that this simplified model reduces itself, in the limit of a long thin axon, to the cable equation used by Hodgkin and Huxley to describe the propagation of action potentials in the unmyelinated squid giant axon. The asymptotic reduction from the simplified PDE model to the cable equation leads to insights that are not otherwise apparent; these include an explanation of why the squid giant axon attains a diameter in the region of 1 mm. The simplified PDE model has more general application than the Hodgkin-Huxley cable equation and can, e.g. be used to describe action potential propagation in myelinated axons and neuronal cell bodies.

  4. Kv2 Channel Regulation of Action Potential Repolarization and Firing Patterns in Superior Cervical Ganglion Neurons and Hippocampal CA1 Pyramidal Neurons

    PubMed Central

    Liu, Pin W.

    2014-01-01

    Kv2 family “delayed-rectifier” potassium channels are widely expressed in mammalian neurons. Kv2 channels activate relatively slowly and their contribution to action potential repolarization under physiological conditions has been unclear. We explored the function of Kv2 channels using a Kv2-selective blocker, Guangxitoxin-1E (GxTX-1E). Using acutely isolated neurons, mixed voltage-clamp and current-clamp experiments were done at 37°C to study the physiological kinetics of channel gating and action potentials. In both rat superior cervical ganglion (SCG) neurons and mouse hippocampal CA1 pyramidal neurons, 100 nm GxTX-1E produced near-saturating block of a component of current typically constituting ∼60–80% of the total delayed-rectifier current. GxTX-1E also reduced A-type potassium current (IA), but much more weakly. In SCG neurons, 100 nm GxTX-1E broadened spikes and voltage clamp experiments using action potential waveforms showed that Kv2 channels carry ∼55% of the total outward current during action potential repolarization despite activating relatively late in the spike. In CA1 neurons, 100 nm GxTX-1E broadened spikes evoked from −70 mV, but not −80 mV, likely reflecting a greater role of Kv2 when other potassium channels were partially inactivated at −70 mV. In both CA1 and SCG neurons, inhibition of Kv2 channels produced dramatic depolarization of interspike voltages during repetitive firing. In CA1 neurons and some SCG neurons, this was associated with increased initial firing frequency. In all neurons, inhibition of Kv2 channels depressed maintained firing because neurons entered depolarization block more readily. Therefore, Kv2 channels can either decrease or increase neuronal excitability depending on the time scale of excitation. PMID:24695716

  5. How Configural Is the Configural Superiority Effect? A Neuroimaging Investigation of Emergent Features in Visual Cortex

    PubMed Central

    Fox, Olivia M.; Harel, Assaf; Bennett, Kevin B.

    2017-01-01

    The perception of a visual stimulus is dependent not only upon local features, but also on the arrangement of those features. When stimulus features are perceptually well organized (e.g., symmetric or parallel), a global configuration with a high degree of salience emerges from the interactions between these features, often referred to as emergent features. Emergent features can be demonstrated in the Configural Superiority Effect (CSE): presenting a stimulus within an organized context relative to its presentation in a disarranged one results in better performance. Prior neuroimaging work on the perception of emergent features regards the CSE as an “all or none” phenomenon, focusing on the contrast between configural and non-configural stimuli. However, it is still not clear how emergent features are processed between these two endpoints. The current study examined the extent to which behavioral and neuroimaging markers of emergent features are responsive to the degree of configurality in visual displays. Subjects were tasked with reporting the anomalous quadrant in a visual search task while being scanned. Degree of configurality was manipulated by incrementally varying the rotational angle of low-level features within the stimulus arrays. Behaviorally, we observed faster response times with increasing levels of configurality. These behavioral changes were accompanied by increases in response magnitude across multiple visual areas in occipito-temporal cortex, primarily early visual cortex and object-selective cortex. Our findings suggest that the neural correlates of emergent features can be observed even in response to stimuli that are not fully configural, and demonstrate that configural information is already present at early stages of the visual hierarchy. PMID:28167924

  6. Comparison of different sets of array configurations for multichannel 2D ERT acquisition

    NASA Astrophysics Data System (ADS)

    Martorana, R.; Capizzi, P.; D'Alessandro, A.; Luzio, D.

    2017-02-01

    Traditional electrode arrays such Wenner-Schlumberger or dipole-dipole are still widely used thanks to their well-known properties but the array configurations are generally not optimized for multi-channel resistivity measures. Synthetic datasets relating to four different arrays, dipole-dipole (DD), pole-dipole (PD), Wenner-Schlumberger (WS) and a modified version of multiple gradient (MG), have been made for a systematic comparison between 2D resistivity models and their inverted images. Different sets of array configurations generated from simple combinations of geometric parameters (potential dipole lengths and dipole separation factors) were tested with synthetic and field data sets, even considering the influence of errors and the acquisition velocity. The purpose is to establish array configurations capable to provide reliable results but, at the same time, not involving excessive survey costs, even linked to the acquiring time and therefore to the number of current dipoles used. For DD, PD and WS arrays a progression of different datasets were considered increasing the number of current dipoles trying to get about the same amount of measures. A multi-coverage MG array configuration is proposed by increasing the lateral coverage and so the number of current dipoles. Noise simulating errors both on the electrode positions and on the electric potential was added. The array configurations have been tested on field data acquired in the landfill site of Bellolampo (Palermo, Italy), to detect and locate the leachate plumes and to identify the HDPE bottom of the landfill. The inversion results were compared using a quantitative analysis of data misfit, relative model resolution and model misfit. The results show that the trends of the first two parameters are linked on the array configuration and that a cumulative analysis of these parameters can help to choose the best array configuration in order to obtain a good resolution and reliability of a survey, according

  7. Road accidents involving bicycles: configurations and injuries.

    PubMed

    Orsi, Chiara; Montomoli, Cristina; Otte, Dietmar; Morandi, Anna

    2017-12-01

    This study analyzed the most common types of accident involving bicycles and compared the frequency of injuries. The data source was the database of German In-Depth Accident Study (GIDAS). Cases consist of bicycles and their riders involved in accidents between 2000 and 2010. In most collisions, the bicycle impacted with a car. The percentage of injured bicyclists was higher in collisions with a heavy vehicle and decreased when the bicycle impacted with lighter vehicles. A high percentage of injured bicyclists in single accidents was observed; the most severe injury was more frequently to head and extremities. Accidents involving a car and a bicycle with the right of way in a bicycle path represented about 20% of involved and injured bicyclists. The ten most frequent configurations represented about 60% of involved and injured bicyclists. These results contribute to understand the dangerous scenarios for bicyclists and to suggest preventive actions.

  8. Na+ current in presynaptic terminals of the crayfish opener cannot initiate action potentials.

    PubMed

    Lin, Jen-Wei

    2016-01-01

    Action potential (AP) propagation in presynaptic axons of the crayfish opener neuromuscular junction (NMJ) was investigated by simultaneously recording from a terminal varicosity and a proximal branch. Although orthodromically conducting APs could be recorded in terminals with amplitudes up to 70 mV, depolarizing steps in terminals to -20 mV or higher failed to fire APs. Patch-clamp recordings did detect Na(+) current (INa) in most terminals. The INa exhibited a high threshold and fast activation rate. Local perfusion of Na(+)-free saline showed that terminal INa contributed to AP waveform by slightly accelerating the rising phase and increasing the peak amplitude. These findings suggest that terminal INa functions to "touch up" but not to generate APs. Copyright © 2016 the American Physiological Society.

  9. Restructured Freedom configuration characteristics

    NASA Technical Reports Server (NTRS)

    Troutman, Patrick A.; Heck, Michael L.; Kumar, Renjith R.; Mazanek, Daniel D.

    1991-01-01

    In Jan. 1991, the LaRc SSFO performed an assessment of the configuration characteristics of the proposed pre-integrated Space Station Freedom (SSF) concept. Of particular concern was the relationship of solar array operation and orientation with respect to spacecraft controllability. For the man-tended configuration (MTC), it was determined that torque equilibrium attitude (TEA) seeking Control Moment Gyroscope (CMG) control laws could not always maintain attitude. The control problems occurred when the solar arrays were tracking the sun to produce full power while flying in an arrow or gravity gradient flight mode. The large solar array articulations that sometimes result from having the functions of the alpha and beta joints reversed on MTC induced large product of inertia changes that can invalidate the control system gains during an orbit. Several modified sun tracking techniques were evaluated with respect to producing a controllable configuration requiring no modifications to the CMG control algorithms. Another assessment involved the permanently manned configuration (PMC) which has a third asymmetric PV unit on one side of the transverse boom. Recommendations include constraining alpha rotations for MTC in the arrow and gravity gradient flight modes and perhaps developing new non-TEA seeking control laws. Recommendations for PMC include raising the operational altitude and moving to a symmetric configuration as soon as possible.

  10. Human ex-vivo action potential model for pro-arrhythmia risk assessment.

    PubMed

    Page, Guy; Ratchada, Phachareeya; Miron, Yannick; Steiner, Guido; Ghetti, Andre; Miller, Paul E; Reynolds, Jack A; Wang, Ken; Greiter-Wilke, Andrea; Polonchuk, Liudmila; Traebert, Martin; Gintant, Gary A; Abi-Gerges, Najah

    2016-01-01

    While current S7B/E14 guidelines have succeeded in protecting patients from QT-prolonging drugs, the absence of a predictive paradigm identifying pro-arrhythmic risks has limited the development of valuable drug programs. We investigated if a human ex-vivo action potential (AP)-based model could provide a more predictive approach for assessing pro-arrhythmic risk in man. Human ventricular trabeculae from ethically consented organ donors were used to evaluate the effects of dofetilide, d,l-sotalol, quinidine, paracetamol and verapamil on AP duration (APD) and recognized pro-arrhythmia predictors (short-term variability of APD at 90% repolarization (STV(APD90)), triangulation (ADP90-APD30) and incidence of early afterdepolarizations at 1 and 2Hz to quantitatively identify the pro-arrhythmic risk. Each drug was blinded and tested separately with 3 concentrations in triplicate trabeculae from 5 hearts, with one vehicle time control per heart. Electrophysiological stability of the model was not affected by sequential applications of vehicle (0.1% dimethyl sulfoxide). Paracetamol and verapamil did not significantly alter anyone of the AP parameters and were classified as devoid of pro-arrhythmic risk. Dofetilide, d,l-sotalol and quinidine exhibited an increase in the manifestation of pro-arrhythmia markers. The model provided quantitative and actionable activity flags and the relatively low total variability in tissue response allowed for the identification of pro-arrhythmic signals. Power analysis indicated that a total of 6 trabeculae derived from 2 hearts are sufficient to identify drug-induced pro-arrhythmia. Thus, the human ex-vivo AP-based model provides an integrative translational assay assisting in shaping clinical development plans that could be used in conjunction with the new CiPA-proposed approach. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Human ex-vivo action potential model for pro-arrhythmia risk assessment

    PubMed Central

    Page, Guy; Ratchada, Phachareeya; Miron, Yannick; Steiner, Guido; Ghetti, Andre; Miller, Paul E; Reynolds, Jack A; Wang, Ken; Greiter-Wilke, Andrea; Polonchuk, Liudmila; Traebert, Martin; Gintant, Gary A; Abi-Gerges, Najah

    2016-01-01

    While current S7B/E14 guidelines have succeeded in protecting patients from QT-prolonging drugs, the absence of a predictive paradigm identifying pro-arrhythmic risks has limited the development of valuable drug programs. We investigated if a human ex-vivo action potential (AP)-based model could provide a more predictive approach for assessing pro-arrhythmic risk in man. Human ventricular trabeculae from ethically consented organ donors were used to evaluate the effects of dofetilide, d,l-sotalol, quinidine, paracetamol and verapamil on AP duration (APD) and recognized pro-arrhythmia predictors (short-term variability of APD at 90% repolarization (STV(APD90)), triangulation (ADP90-APD30) and incidence of early afterdepolarizations at 1 and 2 Hz to quantitatively identify the pro-arrhythmic risk. Each drug was blinded and tested separately with 3 concentrations in triplicate trabeculae from 5 hearts, with one vehicle time control per heart. Electrophysiological stability of the model was not affected by sequential applications of vehicle (0.1% dimethyl sulfoxide). Paracetamol and verapamil did not significantly alter anyone of the AP parameters and were classified as devoid of pro-arrhythmic risk. Dofetilide, d,l-sotalol and quinidine exhibited an increase in the manifestation of pro-arrhythmia markers. The model provided quantitative and actionable activity flags and the relatively low total variability in tissue response allowed for the identification of pro-arrhythmic signals. Power analysis indicated that a total of 6 trabeculae derived from 2 hearts are sufficient to identify drug-induced pro-arrhythmia. Thus, the human ex-vivo AP-based model provides an integrative translational assay assisting in shaping clinical development plans that could be used in conjunction with the new CiPA-proposed approach. PMID:27235787

  12. PIV Logon Configuration Guidance

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lee, Glen Alan

    This document details the configurations and enhancements implemented to support the usage of federal Personal Identity Verification (PIV) Card for logon on unclassified networks. The guidance is a reference implementation of the configurations and enhancements deployed at the Los Alamos National Laboratory (LANL) by Network and Infrastructure Engineering – Core Services (NIE-CS).

  13. 77 FR 45535 - Aldicarb; Proposed Tolerance Actions

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-01

    ... Aldicarb; Proposed Tolerance Actions AGENCY: Environmental Protection Agency (EPA). ACTION: Proposed rule... Information A. Does this action apply to me? You may be potentially affected by this action if you are an... exhaustive, but rather provides a guide for readers regarding entities likely to be affected by this action...

  14. Cardiovascular pleiotropic actions of DPP-4 inhibitors: a step at the cutting edge in understanding their additional therapeutic potentials.

    PubMed

    Balakumar, Pitchai; Dhanaraj, Sokkalingam A

    2013-09-01

    Dipeptidyl peptidase 4 (DPP-4) is a serine protease enzyme expressed widely in many tissues, including the cardiovascular system. The incretin hormones such as glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are released from the small intestine into the vasculature during a meal, and these incretins have a potential to release insulin from pancreatic beta cells of islets of Langerhans, affording a glucose-lowering action. However, both incretins are hurriedly degraded by the DPP-4. Inhibitors of DPP-4, therefore, enhance the bioavailability of GLP-1 and GIP, and thus have been approved for better glycemic management in patients afflicted with type 2 diabetes mellitus (T2DM). Five different DPP-4 inhibitors, often called as 'gliptins', namely sitagliptin, vildagliptin, saxagliptin, linagliptin and alogliptin have been approved hitherto for clinical use. These drugs are used along with diet and exercise to lower blood sugar in diabetic subjects. T2DM is intricately related with an increased risk of cardiovascular disease. Growing body of evidence suggests that gliptins, in addition to their persuasive anti-diabetic action, have a beneficial pleiotropic action on the heart and vessels. In view of the fact of cardiovascular disease susceptibility of patients afflicted with T2DM, gliptins might offer additional therapeutic benefits in treating diabetic cardiovascular complications. Exploring further the cardiovascular pleiotropic potentials of gliptins might open a panorama in impeccably employing these agents for the dual management of T2DM and T2DM-associated perilous cardiovascular complications. This review will shed lights on the newly identified beneficial pleiotropic actions of gliptins on the cardiovascular system. Copyright © 2013 Elsevier Inc. All rights reserved.

  15. Deployable reflector configurations

    NASA Astrophysics Data System (ADS)

    Meinel, A. B.; Meinel, M. P.; Woolf, N. J.

    Both the theoretical reasons for considering a non-circular format for the Large Deployable Reflector, and a potentially realizable concept for such a device, are discussed. The optimum systems for diffraction limited telescopes with incoherent detection have either a single filled aperture, or two such apertures as an interferometer to synthesize a larger aperture. For a single aperture of limited area, a reflector in the form of a slot can be used to give increased angular resolution. It is shown how a 20 x 8 meter telescope can be configured to fit the Space Shuttle bay, and deployed with relatively simple operations. The relationship between the sunshield design and the inclination of the orbit is discussed. The possible use of the LDR as a basic module to permit the construction of supergiant space telescopes and interferometers both for IR/submm studies and for the entire ultraviolet through mm wave spectral region is discussed.

  16. Directed fusion of cardiac spheroids into larger heterocellular microtissues enables investigation of cardiac action potential propagation via cardiac fibroblasts

    PubMed Central

    Markes, Alexander R.; Okundaye, Amenawon O.; Qu, Zhilin; Mende, Ulrike; Choi, Bum-Rak

    2018-01-01

    Multicellular spheroids generated through cellular self-assembly provide cytoarchitectural complexities of native tissue including three-dimensionality, extensive cell-cell contacts, and appropriate cell-extracellular matrix interactions. They are increasingly suggested as building blocks for larger engineered tissues to achieve shapes, organization, heterogeneity, and other biomimetic complexities. Application of these tissue culture platforms is of particular importance in cardiac research as the myocardium is comprised of distinct but intermingled cell types. Here, we generated scaffold-free 3D cardiac microtissue spheroids comprised of cardiac myocytes (CMs) and/or cardiac fibroblasts (CFs) and used them as building blocks to form larger microtissues with different spatial distributions of CMs and CFs. Characterization of fusing homotypic and heterotypic spheroid pairs revealed an important influence of CFs on fusion kinetics, but most strikingly showed rapid fusion kinetics between heterotypic pairs consisting of one CF and one CM spheroid, indicating that CMs and CFs self-sort in vitro into the intermixed morphology found in the healthy myocardium. We then examined electrophysiological integration of fused homotypic and heterotypic microtissues by mapping action potential propagation. Heterocellular elongated microtissues which recapitulate the disproportionate CF spatial distribution seen in the infarcted myocardium showed that action potentials propagate through CF volumes albeit with significant delay. Complementary computational modeling revealed an important role of CF sodium currents and the spatial distribution of the CM-CF boundary in action potential conduction through CF volumes. Taken together, this study provides useful insights for the development of complex, heterocellular engineered 3D tissue constructs and their engraftment via tissue fusion and has implications for arrhythmogenesis in cardiac disease and repair. PMID:29715271

  17. Review article: the potential mechanisms of action of rifaximin in the management of inflammatory bowel diseases.

    PubMed

    Sartor, R B

    2016-01-01

    Gut microbiota dysbiosis contributes to the pathogenesis of inflammatory bowel diseases (IBD). Although the microbiota's role in IBD pathogenesis, specifically Crohn's disease (CD), provides a rationale for antibiotic treatment, antibiotic use in CD remains controversial. Rifaximin, traditionally identified as a nonsystemic bactericidal antibiotic, may be therapeutically beneficial for inducing CD remission. To examine the role of rifaximin in the management of IBD and its potential mechanisms of action. A literature search using the following strategy: ('inflammatory bowel disease' OR 'Crohn's' OR 'ulcerative'), 'rifaximin' AND ('barrier' OR 'translocation' OR 'adhesion' OR 'internalization' OR 'pregnane X'), AND 'pregnane X' AND ('Crohn's' OR 'ulcerative colitis' OR 'inflammatory bowel disease'). In vitro data suggest rifaximin mediates changes in epithelial cell physiology and reduces bacterial attachment and internalisation. In experimental colitis models, rifaximin antagonised the effects of tumour necrosis factor-α on intestinal epithelial cells by activating pregnane X receptor, which inhibits nuclear factor-κB-mediated proinflammatory mediators and induces detoxification genes (e.g. multidrug resistance 1 and cytochrome P450 3A4). Rifaximin also inhibits bacterial translocation into the mesenteric lymph nodes. Accumulating evidence suggests that mechanisms of action of rifaximin in IBD may not be limited to direct bactericidal activity; therefore, rifaximin could potentially be redefined as a gut environment modulator. © 2015 John Wiley & Sons Ltd.

  18. Comparative investigations of manual action representations: evidence that chimpanzees represent the costs of potential future actions involving tools.

    PubMed

    Frey, Scott H; Povinelli, Daniel J

    2012-01-12

    The ability to adjust one's ongoing actions in the anticipation of forthcoming task demands is considered as strong evidence for the existence of internal action representations. Studies of action selection in tool use reveal that the behaviours that we choose in the present moment differ depending on what we intend to do next. Further, they point to a specialized role for mechanisms within the human cerebellum and dominant left cerebral hemisphere in representing the likely sensory costs of intended future actions. Recently, the question of whether similar mechanisms exist in other primates has received growing, but still limited, attention. Here, we present data that bear on this issue from a species that is a natural user of tools, our nearest living relative, the chimpanzee. In experiment 1, a subset of chimpanzees showed a non-significant tendency for their grip preferences to be affected by anticipation of the demands associated with bringing a tool's baited end to their mouths. In experiment 2, chimpanzees' initial grip preferences were consistently affected by anticipation of the forthcoming movements in a task that involves using a tool to extract a food reward. The partial discrepancy between the results of these two studies is attributed to the ability to accurately represent differences between the motor costs associated with executing the two response alternatives available within each task. These findings suggest that chimpanzees are capable of accurately representing the costs of intended future actions, and using those predictions to select movements in the present even in the context of externally directed tool use.

  19. Comparative investigations of manual action representations: evidence that chimpanzees represent the costs of potential future actions involving tools

    PubMed Central

    Frey, Scott H.; Povinelli, Daniel J.

    2012-01-01

    The ability to adjust one's ongoing actions in the anticipation of forthcoming task demands is considered as strong evidence for the existence of internal action representations. Studies of action selection in tool use reveal that the behaviours that we choose in the present moment differ depending on what we intend to do next. Further, they point to a specialized role for mechanisms within the human cerebellum and dominant left cerebral hemisphere in representing the likely sensory costs of intended future actions. Recently, the question of whether similar mechanisms exist in other primates has received growing, but still limited, attention. Here, we present data that bear on this issue from a species that is a natural user of tools, our nearest living relative, the chimpanzee. In experiment 1, a subset of chimpanzees showed a non-significant tendency for their grip preferences to be affected by anticipation of the demands associated with bringing a tool's baited end to their mouths. In experiment 2, chimpanzees' initial grip preferences were consistently affected by anticipation of the forthcoming movements in a task that involves using a tool to extract a food reward. The partial discrepancy between the results of these two studies is attributed to the ability to accurately represent differences between the motor costs associated with executing the two response alternatives available within each task. These findings suggest that chimpanzees are capable of accurately representing the costs of intended future actions, and using those predictions to select movements in the present even in the context of externally directed tool use. PMID:22106426

  20. Analysis of the Capacity Potential of Current Day and Novel Configurations for New York's John F. Kennedy Airport

    NASA Technical Reports Server (NTRS)

    Glaab, Patricia; Tamburro, Ralph; Lee, Paul

    2016-01-01

    In 2015, a series of systems analysis studies were conducted on John F. Kennedy Airport in New York (NY) in a collaborative effort between NASA and the Port Authority of New York and New Jersey (PANYNJ). This work was performed to build a deeper understanding of NY airspace and operations to determine the improvements possible through operational changes with tools currently available, and where new technology is required for additional improvement. The analysis was conducted using tool-based mathematical analyses, video inspection and evaluation using recorded arrival/departure/surface traffic captured by the Aerobahn tool (used by Kennedy Airport for surface metering), and aural data archives available publically through the web to inform the video segments. A discussion of impacts of trajectory and operational choices on capacity is presented, including runway configuration and usage (parallel, converging, crossing, shared, independent, staggered), arrival and departure route characteristics (fix sharing, merges, splits), and how compression of traffic is staged. The authorization in March of 2015 for New York to use reduced spacing under the Federal Aviation Administration (FAA) Wake Turbulence Recategorization (RECAT) also offers significant capacity benefit for New York airports when fully transitioned to the new spacing requirements, and the impact of these changes for New York is discussed. Arrival and departure capacity results are presented for each of the current day Kennedy Airport configurations. While the tools allow many variations of user-selected conditions, the analysis for these studies used arrival-priority, no-winds, additional safety buffer of 5% to the required minimum spacing, and a mix of traffic typical for Kennedy. Two additional "novel" configurations were evaluated. These configurations are of interest to Port Authority and to their airline customers, and are believed to offer near-term capacity benefit with minimal operational and

  1. Sodium Channel Nav1.8 Underlies TTX-Resistant Axonal Action Potential Conduction in Somatosensory C-Fibers of Distal Cutaneous Nerves.

    PubMed

    Klein, Amanda H; Vyshnevska, Alina; Hartke, Timothy V; De Col, Roberto; Mankowski, Joseph L; Turnquist, Brian; Bosmans, Frank; Reeh, Peter W; Schmelz, Martin; Carr, Richard W; Ringkamp, Matthias

    2017-05-17

    Voltage-gated sodium (Na V ) channels are responsible for the initiation and conduction of action potentials within primary afferents. The nine Na V channel isoforms recognized in mammals are often functionally divided into tetrodotoxin (TTX)-sensitive (TTX-s) channels (Na V 1.1-Na V 1.4, Na V 1.6-Na V 1.7) that are blocked by nanomolar concentrations and TTX-resistant (TTX-r) channels (Na V 1.8 and Na V 1.9) inhibited by millimolar concentrations, with Na V 1.5 having an intermediate toxin sensitivity. For small-diameter primary afferent neurons, it is unclear to what extent different Na V channel isoforms are distributed along the peripheral and central branches of their bifurcated axons. To determine the relative contribution of TTX-s and TTX-r channels to action potential conduction in different axonal compartments, we investigated the effects of TTX on C-fiber-mediated compound action potentials (C-CAPs) of proximal and distal peripheral nerve segments and dorsal roots from mice and pigtail monkeys ( Macaca nemestrina ). In the dorsal roots and proximal peripheral nerves of mice and nonhuman primates, TTX reduced the C-CAP amplitude to 16% of the baseline. In contrast, >30% of the C-CAP was resistant to TTX in distal peripheral branches of monkeys and WT and Na V 1.9 -/- mice. In nerves from Na V 1.8 -/- mice, TTX-r C-CAPs could not be detected. These data indicate that Na V 1.8 is the primary isoform underlying TTX-r conduction in distal axons of somatosensory C-fibers. Furthermore, there is a differential spatial distribution of Na V 1.8 within C-fiber axons, being functionally more prominent in the most distal axons and terminal regions. The enrichment of Na V 1.8 in distal axons may provide a useful target in the treatment of pain of peripheral origin. SIGNIFICANCE STATEMENT It is unclear whether individual sodium channel isoforms exert differential roles in action potential conduction along the axonal membrane of nociceptive, unmyelinated peripheral nerve

  2. Action potential-based MEA platform for in vitro screening of drug-induced cardiotoxicity using human iPSCs and rat neonatal myocytes.

    PubMed

    Jans, Danny; Callewaert, Geert; Krylychkina, Olga; Hoffman, Luis; Gullo, Francesco; Prodanov, Dimiter; Braeken, Dries

    2017-09-01

    Drug-induced cardiotoxicity poses a negative impact on public health and drug development. Cardiac safety pharmacology issues urged for the preclinical assessment of drug-induced ventricular arrhythmia leading to the design of several in vitro electrophysiological screening assays. In general, patch clamp systems allow for intracellular recordings, while multi-electrode array (MEA) technology detect extracellular activity. Here, we demonstrate a complementary metal oxide semiconductor (CMOS)-based MEA system as a reliable platform for non-invasive, long-term intracellular recording of cardiac action potentials at high resolution. Quinidine (8 concentrations from 10 -7 to 2.10 -5 M) and verapamil (7 concentrations from 10 -11 to 10 -5 M) were tested for dose-dependent responses in a network of cardiomyocytes. Electrophysiological parameters, such as the action potential duration (APD), rates of depolarization and repolarization and beating frequency were assessed. In hiPSC, quinidine prolonged APD with EC 50 of 2.2·10 -6 M. Further analysis indicated a multifactorial action potential prolongation by quinidine: (1) decreasing fast repolarization with IC 50 of 1.1·10 -6 M; (2) reducing maximum upstroke velocity with IC 50 of 2.6·10 -6 M; and (3) suppressing spontaneous activity with EC 50 of 3.8·10 -6 M. In rat neonatal cardiomyocytes, verapamil blocked spontaneous activity with EC 50 of 5.3·10 -8 M and prolonged the APD with EC 50 of 2.5·10 -8 M. Verapamil reduced rates of fast depolarization and repolarization with IC 50 s of 1.8 and 2.2·10 -7 M, respectively. In conclusion, the proposed action potential-based MEA platform offers high quality and stable long-term recordings with high information content allowing to characterize multi-ion channel blocking drugs. We anticipate application of the system as a screening platform to efficiently and cost-effectively test drugs for cardiac safety. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Effect of contacts configuration and location on selective stimulation of cuff electrode.

    PubMed

    Taghipour-Farshi, Hamed; Frounchi, Javad; Ahmadiasl, Nasser; Shahabi, Parviz; Salekzamani, Yaghoub

    2015-01-01

    Cuff electrodes have been widely used chronically in different clinical applications. Advancements have been made in selective stimulation by using multi-contact cuff electrodes. Steering anodic current is a strategy to increase selectivity by reshaping and localizing electric fields. There are two configurations for contacts to be implemented in cuff, monopolar and tripolar. A cuff electrode with tripolar configuration can restrict the activation to a more localized region within a nerve trunk compared to a cuff with monopolar configuration and improve the selectivity. Anode contacts in tripolar configuration can be made in two structures, "ring" and "dot". In this study, the stimulation capabilities of these two structures were evaluated. The recruitment properties and the selectivity of stimulation were examined by measuring the electric potential produced by stimulation currents. The results of the present study indicated that using dot configuration, the current needed to stimulate fascicles in tripolar topologies would be reduced by 10%. It was also shown that stimulation threshold was increased by moving anode contacts inward the cuff. On the other hand, stimulation threshold was decreased by moving the anode contacts outward the cuff which would decrease selectivity, too. We conclude that dot configuration is a better choice for stimulation. Also, a cuff inward placement of 10% relative to the cuff length was near optimal.

  4. A potential nitrergic mechanism of action for indomethacin, but not of other COX inhibitors: relevance to indomethacin-sensitive headaches.

    PubMed

    Summ, Oliver; Andreou, Anna P; Akerman, Simon; Goadsby, Peter J

    2010-12-01

    Non-steroidal anti-inflammatory drugs (NSAIDs) that act as cyclo-oxygenase (COX) inhibitors are commonly used in the treatment of a range of headache disorders, although their mechanism of action is unclear. Indomethacin is of particular interest given its very special effect in some primary headaches. Here the in vivo technique of intravital microscopy in rats has been utilised as a model of trigeminovascular nociception to study the potential mechanism of action of indomethacin. Dural vascular changes were produced using electrical (neurogenic) dural vasodilation (NDV), calcitonin gene-related peptide (CGRP) induced dural vasodilation and nitric oxide (NO) induced dural vasodilation using NO donors. In each of these settings the effect of intravenously administered indomethacin (5 mg kg(-1)), naproxen (30 mg kg(-1)) and ibuprofen (30 mg kg(-1)) was tested. All of the tested drugs significantly inhibited NDV (between 30 and 52%). Whilst none of them was able to inhibit CGRP-induced dural vasodilation, only indomethacin reduced NO induced dural vasodilation (35 ± 7%, 10 min post administration). We conclude NSAIDs inhibit release of CGRP after NDV without an effect on CGRP directly. Further we describe a differentiating effect of indomethacin inhibiting nitric oxide induced dural vasodilation that is potentially relevant to understanding its unique action in disorders such as paroxysmal hemicrania and hemicrania continua.

  5. Sensitivity Analysis and Optimization of Aerodynamic Configurations with Blend Surfaces

    NASA Technical Reports Server (NTRS)

    Thomas, A. M.; Tiwari, S. N.

    1997-01-01

    A novel (geometrical) parametrization procedure using solutions to a suitably chosen fourth order partial differential equation is used to define a class of airplane configurations. Inclusive in this definition are surface grids, volume grids, and grid sensitivity. The general airplane configuration has wing, fuselage, vertical tail and horizontal tail. The design variables are incorporated into the boundary conditions, and the solution is expressed as a Fourier series. The fuselage has circular cross section, and the radius is an algebraic function of four design parameters and an independent computational variable. Volume grids are obtained through an application of the Control Point Form method. A graphic interface software is developed which dynamically changes the surface of the airplane configuration with the change in input design variable. The software is made user friendly and is targeted towards the initial conceptual development of any aerodynamic configurations. Grid sensitivity with respect to surface design parameters and aerodynamic sensitivity coefficients based on potential flow is obtained using an Automatic Differentiation precompiler software tool ADIFOR. Aerodynamic shape optimization of the complete aircraft with twenty four design variables is performed. Unstructured and structured volume grids and Euler solutions are obtained with standard software to demonstrate the feasibility of the new surface definition.

  6. In-memory interconnect protocol configuration registers

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Cheng, Kevin Y.; Roberts, David A.

    Systems, apparatuses, and methods for moving the interconnect protocol configuration registers into the main memory space of a node. The region of memory used for storing the interconnect protocol configuration registers may also be made cacheable to reduce the latency of accesses to the interconnect protocol configuration registers. Interconnect protocol configuration registers which are used during a startup routine may be prefetched into the host's cache to make the startup routine more efficient. The interconnect protocol configuration registers for various interconnect protocols may include one or more of device capability tables, memory-side statistics (e.g., to support two-level memory data mappingmore » decisions), advanced memory and interconnect features such as repair resources and routing tables, prefetching hints, error correcting code (ECC) bits, lists of device capabilities, set and store base address, capability, device ID, status, configuration, capabilities, and other settings.« less

  7. Utility of action checklists as a consensus building tool

    PubMed Central

    KIM, Yeon-Ha; YOSHIKAWA, Etsuko; YOSHIKAWA, Toru; KOGI, Kazutaka; JUNG, Moon-Hee

    2014-01-01

    The present study’s objective was to determine the mechanisms for enhancing the utility of action checklists applied in participatory approach programs for workplace improvements, to identify the benefits of building consensus and to compare their applicability in Asian countries to find the most appropriate configuration for action checklists. Data were collected from eight trainees and 43 trainers with experience in Participatory Action-Oriented Training. Statistical analysis was performed in SPSS using the package PASW, version 19.0. The difference in the mean score for the degree of the utility of action checklists between countries was analyzed using ANOVA methods. Factor analysis was performed to validate the action checklists’ utility. Pearson Correlation Coefficients were then calculated to determine the direction and strength of the relationship between these factors. Using responses obtained from trainees’ in-depth interviews, we identified 33 key statements that were then classified into 11 thematic clusters. Five factors were extracted, namely “ease of application”, “practical solutions”, “group interaction”, “multifaceted perspective” and “active involvement”. The action checklist was useful for facilitating a participatory process among trainees and trainers for improving working conditions. Action checklists showed similar patterns of utility in various Asian countries; particularly when adjusted to local conditions. PMID:25224334

  8. Comparison between four dissimilar solar panel configurations

    NASA Astrophysics Data System (ADS)

    Suleiman, K.; Ali, U. A.; Yusuf, Ibrahim; Koko, A. D.; Bala, S. I.

    2017-12-01

    Several studies on photovoltaic systems focused on how it operates and energy required in operating it. Little attention is paid on its configurations, modeling of mean time to system failure, availability, cost benefit and comparisons of parallel and series-parallel designs. In this research work, four system configurations were studied. Configuration I consists of two sub-components arranged in parallel with 24 V each, configuration II consists of four sub-components arranged logically in parallel with 12 V each, configuration III consists of four sub-components arranged in series-parallel with 8 V each, and configuration IV has six sub-components with 6 V each arranged in series-parallel. Comparative analysis was made using Chapman Kolmogorov's method. The derivation for explicit expression of mean time to system failure, steady state availability and cost benefit analysis were performed, based on the comparison. Ranking method was used to determine the optimal configuration of the systems. The results of analytical and numerical solutions of system availability and mean time to system failure were determined and it was found that configuration I is the optimal configuration.

  9. An automated system using spatial oversampling for optical mapping in murine atria. Development and validation with monophasic and transmembrane action potentials.

    PubMed

    Yu, Ting Yue; Syeda, Fahima; Holmes, Andrew P; Osborne, Benjamin; Dehghani, Hamid; Brain, Keith L; Kirchhof, Paulus; Fabritz, Larissa

    2014-08-01

    We developed and validated a new optical mapping system for quantification of electrical activation and repolarisation in murine atria. The system makes use of a novel 2nd generation complementary metal-oxide-semiconductor (CMOS) camera with deliberate oversampling to allow both assessment of electrical activation with high spatial and temporal resolution (128 × 2048 pixels) and reliable assessment of atrial murine repolarisation using post-processing of signals. Optical recordings were taken from isolated, superfused and electrically stimulated murine left atria. The system reliably describes activation sequences, identifies areas of functional block, and allows quantification of conduction velocities and vectors. Furthermore, the system records murine atrial action potentials with comparable duration to both monophasic and transmembrane action potentials in murine atria. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  10. Configuration Management Plan for K Basins

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Weir, W.R.; Laney, T.

    This plan describes a configuration management program for K Basins that establishes the systems, processes, and responsibilities necessary for implementation. The K Basins configuration management plan provides the methodology to establish, upgrade, reconstitute, and maintain the technical consistency among the requirements, physical configuration, and documentation. The technical consistency afforded by this plan ensures accurate technical information necessary to achieve the mission objectives that provide for the safe, economic, and environmentally sound management of K Basins and the stored material. The configuration management program architecture presented in this plan is based on the functional model established in the DOE Standard, DOE-STD-1073-93,more » {open_quotes}Guide for Operational Configuration Management Program{close_quotes}.« less

  11. Potential Mechanisms of Action of Dietary Phytochemicals for Cancer Prevention by Targeting Cellular Signaling Transduction Pathways.

    PubMed

    Chen, Hongyu; Liu, Rui Hai

    2018-04-04

    Cancer is a severe health problem that significantly undermines life span and quality. Dietary approach helps provide preventive, nontoxic, and economical strategies against cancer. Increased intake of fruits, vegetables, and whole grains are linked to reduced risk of cancer and other chronic diseases. The anticancer activities of plant-based foods are related to the actions of phytochemicals. One potential mechanism of action of anticancer phytochemicals is that they regulate cellular signal transduction pathways and hence affects cancer cell behaviors such as proliferation, apoptosis, and invasion. Recent publications have reported phytochemicals to have anticancer activities through targeting a wide variety of cell signaling pathways at different levels, such as transcriptional or post-transcriptional regulation, protein activation and intercellular messaging. In this review, we discuss major groups of phytochemicals and their regulation on cell signaling transduction against carcinogenesis via key participators, such as Nrf2, CYP450, MAPK, Akt, JAK/STAT, Wnt/β-catenin, p53, NF-κB, and cancer-related miRNAs.

  12. Density effects on electronic configurations in dense plasmas

    NASA Astrophysics Data System (ADS)

    Faussurier, Gérald; Blancard, Christophe

    2018-02-01

    We present a quantum mechanical model to describe the density effects on electronic configurations inside a plasma environment. Two different approaches are given by starting from a quantum average-atom model. Illustrations are shown for an aluminum plasma in local thermodynamic equilibrium at solid density and at a temperature of 100 eV and in the thermodynamic conditions of a recent experiment designed to characterize the effects of the ionization potential depression treatment. Our approach compares well with experiment and is consistent in that case with the approach of Stewart and Pyatt to describe the ionization potential depression rather than with the method of Ecker and Kröll.

  13. Configurations of Activity: From the Coupling of Individual Actions to the Emergence of Collective Activity. A Study of Mathematics Teaching Situation in Primary School

    ERIC Educational Resources Information Center

    Veyrunes, Philippe; Gal-Petitfaux, Nathalie; Durand, Marc

    2009-01-01

    This article presents and uses the notion of configuration of activity, which extends the Norbert Elias's original concept of social configuration based on the study and analysis of individual and collective activity. Although this concept embraces all types of social activities, in the present study the authors used it to describe and analyse…

  14. Use of sensory and motor action potentials to identify the position of trigeminal nerve divisions for radiofrequency thermocoagulation.

    PubMed

    Lin, Bo; Lu, Xuguang; Zhai, Xinli; Cai, Zhigang

    2014-12-01

    The objective of this study was to develop an electrophysiological method for intraoperative localization of the trigeminal nerve branches during radiofrequency thermocoagulation (RFTC). Twenty-three patients who were scheduled to undergo RFTC were included. The trigeminal nerve root was stimulated through the foramen ovale using the radiofrequency cannula. Antidromic responses were recorded from the target division through supraorbital, infraorbital, and mental foramina electrodes, and an additional electrode at the masseter muscle. Sensory and motor action responses, as well as verbal and masseter contraction responses, were recorded and correlated. The antidromic responses were easily recorded in the target division in all 23 patients, and they were invariably correlated with the patient's verbal responses. The potentials were recorded successively from V1 to V3. The amplitude in each division before and after RFTC showed little difference in response to electrical stimulation with the same current. The motor trigeminal nerve action potentials were recorded in 10 patients; 7 of these patients had postoperative masseter muscle weakness, while the remaining 3 had normal masseter muscle function. Potentials with low amplitudes were usually obtained from neighboring divisions, but no unexpected denervation of any branches was observed. All the patients experienced immediate pain relief after the procedure. This technique is sensitive and easy to apply. The sensory and motor potentials matched the verbal responses and the complications. Although it cannot completely substitute for the patient's verbal response, this approach is helpful in uncooperative patients, and it predicts and reduces the incidence of masseter muscle weakness. The use of these complementary techniques could increase the chances of treatment success.

  15. Action potential influences spatial perception: Evidence for genuine top-down effects on perception.

    PubMed

    Witt, Jessica K

    2017-08-01

    The action-specific account of spatial perception asserts that a perceiver's ability to perform an action, such as hitting a softball or walking up a hill, impacts the visual perception of the target object. Although much evidence is consistent with this claim, the evidence has been challenged as to whether perception is truly impacted, as opposed to the responses themselves. These challenges have recently been organized as six pitfalls that provide a framework with which to evaluate the empirical evidence. Four case studies of action-specific effects are offered as evidence that meets the framework's high bar, and thus that demonstrates genuine perceptual effects. That action influences spatial perception is evidence that perceptual and action-related processes are intricately and bidirectionally linked.

  16. Response of Seismometer with Symmetric Triaxial Sensor Configuration to Complex Ground Motion

    NASA Astrophysics Data System (ADS)

    Graizer, V.

    2007-12-01

    Most instruments used in seismological practice to record ground motion in all directions use three sensors oriented toward North, East and upward. In this standard configuration horizontal and vertical sensors differ in their construction because of gravity acceleration always applied to a vertical sensor. An alternative way of symmetric sensor configuration was first introduced by Galperin (1955) for petroleum exploration. In this arrangement three identical sensors are also positioned orthogonally to each other but are tilted at the same angle of 54.7 degrees to the vertical axis (triaxial system of coordinate balanced on its corner). Records obtained using symmetric configuration must be rotated into an earth referenced X, Y, Z coordinate system. A number of recent seismological instruments (e.g., broadband seismometers Streckeisen STS-2, Trillium of Nanometrics and Cronos of Kinemetrics) are using symmetric sensor configuration. In most of seismological studies it is assumed that rotational (rocking and torsion) components of earthquake ground motion are small enough to be neglected. However, recently examples were shown when rotational components are significant relative to translational components of motions. Response of pendulums installed in standard configuration (vertical and two horizontals) to complex input motion that includes rotations has been studied in a number of publications. We consider the response of pendulums in a symmetric sensor configuration to complex input motions including rotations, and the resultant triaxial system response. Possible implications of using symmetric sensor configuration in strong motion studies are discussed. Considering benefits of equal design of all three sensors in symmetric configuration, and as a result potentially lower cost of the three-component accelerograph, it may be useful for strong motion measurements not requiring high resolution post signal processing. The disadvantage of this configuration is that if

  17. Small Launch Vehicle Concept Development for Affordable Multi-Stage Inline Configurations

    NASA Technical Reports Server (NTRS)

    Beers, Benjamin R.; Waters, Eric D.; Philips, Alan D.; Threet, Grady E., Jr.

    2014-01-01

    The Advanced Concepts Office at NASA's George C. Marshall Space Flight Center conducted a study of two configurations of a three stage, inline, liquid propellant small launch vehicle concept developed on the premise of maximizing affordability by targeting a specific payload capability range based on current industry demand. The initial configuration, NESC-1, employed liquid oxygen as the oxidizer and rocket propellant grade kerosene as the fuel in all three stages. The second and more heavily studied configuration, NESC-4, employed liquid oxygen and rocket propellant grade kerosene on the first and second stages and liquid oxygen and liquid methane fuel on the third stage. On both vehicles, sensitivity studies were first conducted on specific impulse and stage propellant mass fraction in order to baseline gear ratios and drive the focus of concept development. Subsequent sensitivity and trade studies on the NESC-4 configuration investigated potential impacts to affordability due to changes in gross liftoff weight and/or vehicle complexity. Results are discussed at a high level to understand the severity of certain sensitivities and how those trade studies conducted can either affect cost, performance or both.

  18. Development of a Jet Noise Prediction Method for Installed Jet Configurations

    NASA Technical Reports Server (NTRS)

    Hunter, Craig A.; Thomas, Russell H.

    2003-01-01

    This paper describes development of the Jet3D noise prediction method and its application to heated jets with complex three-dimensional flow fields and installation effects. Noise predictions were made for four separate flow bypass ratio five nozzle configurations tested in the NASA Langley Jet Noise Laboratory. These configurations consist of a round core and fan nozzle with and without pylon, and an eight chevron core nozzle and round fan nozzle with and without pylon. Predicted SPL data were in good agreement with experimental noise measurements up to 121 inlet angle, beyond which Jet3D under predicted low frequency levels. This is due to inherent limitations in the formulation of Lighthill's Acoustic Analogy used in Jet3D, and will be corrected in ongoing development. Jet3D did an excellent job predicting full scale EPNL for nonchevron configurations, and captured the effect of the pylon, correctly predicting a reduction in EPNL. EPNL predictions for chevron configurations were not in good agreement with measured data, likely due to the lower mixing and longer potential cores in the CFD simulations of these cases.

  19. Short latency compound action potentials from mammalian gravity receptor organs

    NASA Technical Reports Server (NTRS)

    Jones, T. A.; Jones, S. M.

    1999-01-01

    Gravity receptor function was characterized in four mammalian species using far-field vestibular evoked potentials (VsEPs). VsEPs are compound action potentials of the vestibular nerve and central relays that are elicited by linear acceleration ramps applied to the cranium. Rats, mice, guinea pigs, and gerbils were studied. In all species, response onset occurred within 1.5 ms of the stimulus onset. Responses persisted during intense (116 dBSPL) wide-band (50 to 50 inverted question mark omitted inverted question mark000 Hz) forward masking, whereas auditory responses to intense clicks (112 dBpeSPL) were eliminated under the same conditions. VsEPs remained after cochlear extirpation but were eliminated following bilateral labyrinthectomy. Responses included a series of positive and negative peaks that occurred within 8 ms of stimulus onset (range of means at +6 dBre: 1.0 g/ms: P1=908 to 1062 micros, N1=1342 to 1475 micros, P2=1632 to 1952 micros, N2=2038 to 2387 micros). Mean response amplitudes at +6 dBre: 1.0 g/ms ranged from 0.14 to 0.99 microV. VsEP input/output functions revealed latency slopes that varied across peaks and species ranging from -19 to -51 micros/dB. Amplitude-intensity slopes also varied ranging from 0.04 to 0.08 microV/dB for rats and mice. Latency values were comparable to those of birds although amplitudes were substantially smaller in mammals. VsEP threshold values were considerably higher in mammals compared to birds and ranged from -8.1 to -10.5 dBre 1.0 g/ms across species. These results support the hypothesis that mammalian gravity receptors are less sensitive to dynamic stimuli than are those of birds.

  20. Conduction velocity of antigravity muscle action potentials.

    PubMed

    Christova, L; Kosarov, D; Christova, P

    1992-01-01

    The conduction velocity of the impulses along the muscle fibers is one of the parameters of the extraterritorial potentials of the motor units allowing for the evaluation of the functional state of the muscles. There are no data about the conduction velocities of antigravity muscleaction potentials. In this paper we offer a method for measuring conduction velocity of potentials of single MUs and the averaged potentials of the interference electromiogram (IEMG) lead-off by surface electrodes from mm. sternocleidomastoideus, trapezius, deltoideus (caput laterale) and vastus medialis. The measured mean values of the conduction velocity of antigravity muscles potentials can be used for testing the functional state of the muscles.