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Sample records for action potential model

  1. Cardiac dynamics: a simplified model for action potential propagation

    PubMed Central

    2012-01-01

    This paper analyzes a new semiphysiological ionic model, used recently to study reexitations and reentry in cardiac tissue [I.R. Cantalapiedra et al, PRE 82 011907 (2010)]. The aim of the model is to reproduce action potencial morphologies and restitution curves obtained, either from experimental data, or from more complex electrophysiological models. The model divides all ion currents into four groups according to their function, thus resulting into fast-slow and inward-outward currents. We show that this simplified model is flexible enough as to accurately capture the electrical properties of cardiac myocytes, having the advantage of being less computational demanding than detailed electrophysiological models. Under some conditions, it has been shown to be amenable to mathematical analysis. The model reproduces the action potential (AP) change with stimulation rate observed both experimentally and in realistic models of healthy human and guinea pig myocytes (TNNP and LRd models, respectively). When simulated in a cable it also gives the right dependence of the conduction velocity (CV) with stimulation rate. Besides reproducing correctly these restitution properties, it also gives a good fit for the morphology of the AP, including the notch typical of phase 1. Finally, we perform simulations in a realistic geometric model of the rabbit’s ventricles, finding a good qualitative agreement in AP propagation and the ECG. Thus, this simplified model represents an alternative to more complex models when studying instabilities in wave propagation. PMID:23194429

  2. Modelling Action Potential Generation and Propagation in Fibroblastic Cells

    NASA Astrophysics Data System (ADS)

    Torres, J. J.; Cornelisse, L. N.; Harks, E. G. A.; Theuvenet, A. P. R.; Ypey, D. L.

    2003-04-01

    Using a standard Hodgkin-Huxley (HH) formalism, we present a mathematical model for action potential (AP) generation and intercellular AP propagation in quiescent (serum-deprived) normal rat kidney (NRK) fibroblasts [1], based on the recent experimental identification of the ion channels involved [2]. The principal ion channels described are those of an inwardly rectifying K+ conductance (GKIR), an L-type calcium conductance (GCaL), an intracellular calcium activated Cl- conductance (GCl(Ca)), a residual leak conductance Gleak, and gap junctional channels between the cells (Ggj). The role of each one of these components in the particular shape of the AP wave-form has been analyzed and compared with experimental observations. In addition, we have studied the role of subcellular processes like intracellular calcium dynamics and calcium buffering in AP generation. AP propagation between cells was reconstructed in a hexagonal model of cells coupled by Ggj with physiological conductance values. The model revealed an excitability mechanism of quiescent NRK cells with a particular role of intracellular calcium dynamics. It allows further explorations of the mechanism of signal generation and transmission in NRK cell cultures and its dependence on growth conditions.

  3. 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.

  4. 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 %. PMID:27016364

  5. Simulation of ECG Repolarization Phase with Improved Model of Cell Action Potentials

    NASA Astrophysics Data System (ADS)

    Trobec, Roman; Depolli, Matjaž; Avbelj, Viktor

    An improved model of action potentials (AP) is proposed to increase the accuracy of simulated electrocardiograms (ECGs). ECG simulator is based on a spatial model of a left ventricle, composed of cubic cells. Three distinct APs, modeled with functions proposed by Wohlfard, have been assigned to the cells, forming epicardial, mid, and endocardial layers. Identification of exact parameter values for AP models has been done through optimization of the simulated ECGs. Results have shown that only through an introduction of a minor extension to the AP model, simulator is able to produce more realistic ECGs. The same extension also proves essential for achieving a better fit between the measured and modeled APs.

  6. Computational and Electronic Analog Implementation of the Hodgkin-Huxley Model of Action Potentials in Neurons

    NASA Astrophysics Data System (ADS)

    Smith, Peter; Link, Justin

    2012-02-01

    Alan Loyd Hodgkin and Andrew Huxley's mathematical model of action potential initiation and propagation in neurons is one of the greatest hallmarks of biophysics. Two techniques for implementing the Hodgkin-Huxley model were explored: computational and electronic analog. Computational modeling was done using NEURON 7.1. NEURON is a free, robust, and relatively user friendly simulation environment that enables quantitatively accurate computational modeling of neurons and neural networks. An analog electronic circuit was built using field-effect transistors (FETs) to simulate the non-linear, voltage-dependent (sodium and potassium) conductances that are responsible for membrane excitability. While the electronic analog qualitatively reproduces many of the key features of the action potential including overall shape, inactivation period, and propagation, it was difficult to quantitatively reproduce the Hodgkin-Huxley model. In addition, while the relative cost to build circuits equivalent to small membrane patches is minimal (˜50), implementation of larger cells or networks would prove uneconomical. Still, both techniques are viable avenues toward introducing interdisciplinary research into either a computational or electronics lab setting at the undergraduate level.

  7. 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

  8. Action potential generation in an anatomically constrained model of medial superior olive axons.

    PubMed

    Lehnert, Simon; Ford, Marc C; Alexandrova, Olga; Hellmundt, Franziska; Felmy, Felix; Grothe, Benedikt; Leibold, Christian

    2014-04-01

    Neurons in the medial superior olive (MSO) encode interaural time differences (ITDs) with sustained firing rates of >100 Hz. They are able to generate such high firing rates for several hundred milliseconds despite their extremely low-input resistances of only few megaohms and high synaptic conductances in vivo. The biophysical mechanisms by which these leaky neurons maintain their excitability are not understood. Since action potentials (APs) are usually assumed to be generated in the axon initial segment (AIS), we analyzed anatomical data of proximal MSO axons in Mongolian gerbils and found that the axon diameter is <1 μm and the internode length is ∼100 μm. Using a morphologically constrained computational model of the MSO axon, we show that these thin axons facilitate the excitability of the AIS. However, for ongoing high rates of synaptic inputs the model generates a substantial fraction of APs in its nodes of Ranvier. These distally initiated APs are mediated by a spatial gradient of sodium channel inactivation and a strong somatic current sink. The model also predicts that distal AP initiation increases the dynamic range of the rate code for ITDs. PMID:24719114

  9. Calcium Transients Closely Reflect Prolonged Action Potentials in iPSC Models of Inherited Cardiac Arrhythmia

    PubMed Central

    Spencer, C. Ian; Baba, Shiro; Nakamura, Kenta; Hua, Ethan A.; Sears, Marie A.F.; Fu, Chi-cheng; Zhang, Jianhua; Balijepalli, Sadguna; Tomoda, Kiichiro; Hayashi, Yohei; Lizarraga, Paweena; Wojciak, Julianne; Scheinman, Melvin M.; Aalto-Setälä, Katriina; Makielski, Jonathan C.; January, Craig T.; Healy, Kevin E.; Kamp, Timothy J.; Yamanaka, Shinya; Conklin, Bruce R.

    2014-01-01

    Summary Long-QT syndrome mutations can cause syncope and sudden death by prolonging the cardiac action potential (AP). Ion channels affected by mutations are various, and the influences of cellular calcium cycling on LQTS cardiac events are unknown. To better understand LQTS arrhythmias, we performed current-clamp and intracellular calcium ([Ca2+]i) measurements on cardiomyocytes differentiated from patient-derived induced pluripotent stem cells (iPS-CM). In myocytes carrying an LQT2 mutation (HERG-A422T), APs and [Ca2+]i transients were prolonged in parallel. APs were abbreviated by nifedipine exposure and further lengthened upon releasing intracellularly stored Ca2+. Validating this model, control iPS-CM treated with HERG-blocking drugs recapitulated the LQT2 phenotype. In LQT3 iPS-CM, expressing NaV1.5-N406K, APs and [Ca2+]i transients were markedly prolonged. AP prolongation was sensitive to tetrodotoxin and to inhibiting Na+-Ca2+ exchange. These results suggest that LQTS mutations act partly on cytosolic Ca2+ cycling, potentially providing a basis for functionally targeted interventions regardless of the specific mutation site. PMID:25254341

  10. Variety of the Wave Change in Compound Muscle Action Potential in an Animal Model

    PubMed Central

    Ito, Zenya; Ando, Kei; Muramoto, Akio; Kobayashi, Kazuyoshi; Hida, Tetsuro; Ito, Kenyu; Ishikawa, Yoshimoto; Tsushima, Mikito; Matsumoto, Akiyuki; Tanaka, Satoshi; Morozumi, Masayoshi; Matsuyama, Yukihiro; Ishiguro, Naoki

    2015-01-01

    Study Design Animal study. Purpose To review the present warning point criteria of the compound muscle action potential (CMAP) and investigate new criteria for spinal surgery safety using an animal model. Overview of Literature Little is known about correlation palesis and amplitude of spinal cord monitoring. Methods After laminectomy of the tenth thoracic spinal lamina, 2-140 g force was delivered to the spinal cord with a tension gage to create a bilateral contusion injury. The study morphology change of the CMAP wave and locomotor scale were evaluated for one month. Results Four different types of wave morphology changes were observed: no change, amplitude decrease only, morphology change only, and amplitude and morphology change. Amplitude and morphology changed simultaneously and significantly as the injury force increased (p<0.05) Locomotor scale in the amplitude and morphology group worsened more than the other groups. Conclusions Amplitude and morphology change of the CMAP wave exists and could be the key of the alarm point in CMAP. PMID:26713129

  11. 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.

  12. Action potential processing in a detailed Purkinje cell model reveals a critical role for axonal compartmentalization

    PubMed Central

    Masoli, Stefano; Solinas, Sergio; D'Angelo, Egidio

    2015-01-01

    The Purkinje cell (PC) is among the most complex neurons in the brain and plays a critical role for cerebellar functioning. PCs operate as fast pacemakers modulated by synaptic inputs but can switch from simple spikes to complex bursts and, in some conditions, show bistability. In contrast to original works emphasizing dendritic Ca-dependent mechanisms, recent experiments have supported a primary role for axonal Na-dependent processing, which could effectively regulate spike generation and transmission to deep cerebellar nuclei (DCN). In order to account for the numerous ionic mechanisms involved (at present including Nav1.6, Cav2.1, Cav3.1, Cav3.2, Cav3.3, Kv1.1, Kv1.5, Kv3.3, Kv3.4, Kv4.3, KCa1.1, KCa2.2, KCa3.1, Kir2.x, HCN1), we have elaborated a multicompartmental model incorporating available knowledge on localization and gating of PC ionic channels. The axon, including initial segment (AIS) and Ranvier nodes (RNs), proved critical to obtain appropriate pacemaking and firing frequency modulation. Simple spikes initiated in the AIS and protracted discharges were stabilized in the soma through Na-dependent mechanisms, while somato-dendritic Ca channels contributed to sustain pacemaking and to generate complex bursting at high discharge regimes. Bistability occurred only following Na and Ca channel down-regulation. In addition, specific properties in RNs K currents were required to limit spike transmission frequency along the axon. The model showed how organized electroresponsive functions could emerge from the molecular complexity of PCs and showed that the axon is fundamental to complement ionic channel compartmentalization enabling action potential processing and transmission of specific spike patterns to DCN. PMID:25759640

  13. Simulation of the undiseased human cardiac ventricular action potential: model formulation and experimental validation.

    PubMed

    O'Hara, Thomas; Virág, László; Varró, András; Rudy, Yoram

    2011-05-01

    Cellular electrophysiology experiments, important for understanding cardiac arrhythmia mechanisms, are usually performed with channels expressed in non myocytes, or with non-human myocytes. Differences between cell types and species affect results. Thus, an accurate model for the undiseased human ventricular action potential (AP) which reproduces a broad range of physiological behaviors is needed. Such a model requires extensive experimental data, but essential elements have been unavailable. Here, we develop a human ventricular AP model using new undiseased human ventricular data: Ca(2+) versus voltage dependent inactivation of L-type Ca(2+) current (I(CaL)); kinetics for the transient outward, rapid delayed rectifier (I(Kr)), Na(+)/Ca(2+) exchange (I(NaCa)), and inward rectifier currents; AP recordings at all physiological cycle lengths; and rate dependence and restitution of AP duration (APD) with and without a variety of specific channel blockers. Simulated APs reproduced the experimental AP morphology, APD rate dependence, and restitution. Using undiseased human mRNA and protein data, models for different transmural cell types were developed. Experiments for rate dependence of Ca(2+) (including peak and decay) and intracellular sodium ([Na(+)](i)) in undiseased human myocytes were quantitatively reproduced by the model. Early afterdepolarizations were induced by I(Kr) block during slow pacing, and AP and Ca(2+) alternans appeared at rates >200 bpm, as observed in the nonfailing human ventricle. Ca(2+)/calmodulin-dependent protein kinase II (CaMK) modulated rate dependence of Ca(2+) cycling. I(NaCa) linked Ca(2+) alternation to AP alternans. CaMK suppression or SERCA upregulation eliminated alternans. Steady state APD rate dependence was caused primarily by changes in [Na(+)](i), via its modulation of the electrogenic Na(+)/K(+) ATPase current. At fast pacing rates, late Na(+) current and I(CaL) were also contributors. APD shortening during restitution was

  14. Uncertainty and variability in models of the cardiac action potential: Can we build trustworthy models?

    PubMed

    Johnstone, Ross H; Chang, Eugene T Y; Bardenet, Rémi; de Boer, Teun P; Gavaghan, David J; Pathmanathan, Pras; Clayton, Richard H; Mirams, Gary R

    2016-07-01

    Cardiac electrophysiology models have been developed for over 50years, and now include detailed descriptions of individual ion currents and sub-cellular calcium handling. It is commonly accepted that there are many uncertainties in these systems, with quantities such as ion channel kinetics or expression levels being difficult to measure or variable between samples. Until recently, the original approach of describing model parameters using single values has been retained, and consequently the majority of mathematical models in use today provide point predictions, with no associated uncertainty. In recent years, statistical techniques have been developed and applied in many scientific areas to capture uncertainties in the quantities that determine model behaviour, and to provide a distribution of predictions which accounts for this uncertainty. In this paper we discuss this concept, which is termed uncertainty quantification, and consider how it might be applied to cardiac electrophysiology models. We present two case studies in which probability distributions, instead of individual numbers, are inferred from data to describe quantities such as maximal current densities. Then we show how these probabilistic representations of model parameters enable probabilities to be placed on predicted behaviours. We demonstrate how changes in these probability distributions across data sets offer insight into which currents cause beat-to-beat variability in canine APs. We conclude with a discussion of the challenges that this approach entails, and how it provides opportunities to improve our understanding of electrophysiology. PMID:26611884

  15. Complex Dynamic Thresholds and Generation of the Action Potentials in the Neural-Activity Model

    NASA Astrophysics Data System (ADS)

    Kirillov, S. Yu.; Nekorkin, V. I.

    2016-05-01

    This work is devoted to studying the processes of activation of the neurons whose excitation thresholds are not constant and vary in time (the so-called dynamic thresholds). The neuron dynamics is described by the FitzHugh-Nagumo model with nonlinear behavior of the recovery variable. The neuron response to the external pulsed activating action in the presence of a slowly varying synaptic current is studied within the framework of this model. The structure of the dynamic threshold is studied and its properties depending on the external-action parameters are established. It is found that the formation of the "folds" in the separatrix threshold manifold in the model phase space is a typical feature of the complex dynamic threshold. High neuron sensitivity to the action of the comparatively weak slow control signals is established. This explains the capability of the neurons to perform flexible tuning of their selective properties for detecting various external signals in sufficiently short times (of the order of duration of several spikes).

  16. Complex Dynamic Thresholds and Generation of the Action Potentials in the Neural-Activity Model

    NASA Astrophysics Data System (ADS)

    Kirillov, S. Yu.; Nekorkin, V. I.

    2016-06-01

    This work is devoted to studying the processes of activation of the neurons whose excitation thresholds are not constant and vary in time (the so-called dynamic thresholds). The neuron dynamics is described by the FitzHugh-Nagumo model with nonlinear behavior of the recovery variable. The neuron response to the external pulsed activating action in the presence of a slowly varying synaptic current is studied within the framework of this model. The structure of the dynamic threshold is studied and its properties depending on the external-action parameters are established. It is found that the formation of the "folds" in the separatrix threshold manifold in the model phase space is a typical feature of the complex dynamic threshold. High neuron sensitivity to the action of the comparatively weak slow control signals is established. This explains the capability of the neurons to perform flexible tuning of their selective properties for detecting various external signals in sufficiently short times (of the order of duration of several spikes).

  17. [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. PMID:27079105

  18. A model of the magnetic fields created by single motor unit compound action potentials in skeletal muscle.

    PubMed

    Parker, K K; Wikswo, J P

    1997-10-01

    We have developed a computationally simple model for calculating the magnetic-field strength at a point due to a single motor unit compound action potential (SMUCAP). The motor unit is defined only in terms of its anatomical features, and the SMUCAP is approximated using the tripole model. The distributed current density J is calculated within the volume defined by the motor unit. The law of Biot and Savart can then be cast in a form necessitating that J be integrated only over the region containing current sources or conductivity boundaries. The magnetic-field strength is defined as the summation of the contributions to the field made by every muscle fiber in the motor unit. Applying this model to SMUCAP measurements obtained using a high-resolution SUper Conducting Quantum Interference Device (SQUID) magnetometer may yield information regarding the distribution of action currents (AC's) and the anatomical properties of single motor units within a muscle bundle. PMID:9311164

  19. Analytical solutions of the Frankenhaeuser-Huxley equations I: minimal model for backpropagation of action potentials in sparsely excitable dendrites.

    PubMed

    Poznanski, Roman R

    2004-09-01

    Hodgkin and Huxley's ionic theory of the nerve impulse embodies principles, applicable also to the impulses in vertebrate nerve fibers, as demonstrated by Bernhard Frankenhaeuser and Andrew Huxley 40 years ago. Frankenhaeuser and Huxley reformulated the classical Hodgkin-Huxley equations, in terms of electrodiffusion theory, and computed action potentials specifically for saltatory conduction in myelinated axons. In this paper, we obtain analytical solutions to the most difficult nonlinear partial differential equations in classical neurophysiology. We solve analytically the Frankenhaeuser-Huxley equations pertaining to a model of sparsely excitable, nonlinear dendrites with clusters of transiently activating, TTX-sensitive Na(+) channels, discretely distributed as point sources of inward current along a continuous (non-segmented) leaky cable structure. Each cluster or hot-spot, corresponding to a mesoscopic level description of Na(+) ion channels, includes known cumulative inactivation kinetics observed at the microscopic level. In such a third-order system, the 'recovery' variable is an electrogenic sodium-pump imbedded in the passive membrane, and the system is stabilized by the presence of a large leak conductance mediated by a composite number of ligand-gated channels permeable to monovalent cations Na(+) and K(+). In order to reproduce antidromic propagation and attenuation of action potentials, a nonlinear integral equation must be solved (in the presence of suprathreshold input, and a constant-field equation of electrodiffusion at each hot-spot with membrane gates controlling the flow of current). A perturbative expansion of the non-dimensional membrane potential (Phi) is used to obtain time-dependent analytical solutions, involving a voltage-dependent Na(+) activation (micro) and a state-dependent inactivation (eta) gating variables. It is shown that action potentials attenuate in amplitude in accordance with experimental findings, and that the spatial

  20. Computational modeling of inhibition of voltage-gated Ca channels: identification of different effects on uterine and cardiac action potentials

    PubMed Central

    Tong, Wing-Chiu; Ghouri, Iffath; Taggart, Michael J.

    2014-01-01

    The uterus and heart share the important physiological feature whereby contractile activation of the muscle tissue is regulated by the generation of periodic, spontaneous electrical action potentials (APs). Preterm birth arising from premature uterine contractions is a major complication of pregnancy and there remains a need to pursue avenues of research that facilitate the use of drugs, tocolytics, to limit these inappropriate contractions without deleterious actions on cardiac electrical excitation. A novel approach is to make use of mathematical models of uterine and cardiac APs, which incorporate many ionic currents contributing to the AP forms, and test the cell-specific responses to interventions. We have used three such models—of uterine smooth muscle cells (USMC), cardiac sinoatrial node cells (SAN), and ventricular cells—to investigate the relative effects of reducing two important voltage-gated Ca currents—the L-type (ICaL) and T-type (ICaT) Ca currents. Reduction of ICaL (10%) alone, or ICaT (40%) alone, blunted USMC APs with little effect on ventricular APs and only mild effects on SAN activity. Larger reductions in either current further attenuated the USMC APs but with also greater effects on SAN APs. Encouragingly, a combination of ICaL and ICaT reduction did blunt USMC APs as intended with little detriment to APs of either cardiac cell type. Subsequent overlapping maps of ICaL and ICaT inhibition profiles from each model revealed a range of combined reductions of ICaL and ICaT over which an appreciable diminution of USMC APs could be achieved with no deleterious action on cardiac SAN or ventricular APs. This novel approach illustrates the potential for computational biology to inform us of possible uterine and cardiac cell-specific mechanisms. Incorporating such computational approaches in future studies directed at designing new, or repurposing existing, tocolytics will be beneficial for establishing a desired uterine specificity of action

  1. Correlation of action potentials in adjacent neurons

    NASA Astrophysics Data System (ADS)

    Shneider, M. N.; Pekker, M.

    2015-12-01

    A possible mechanism for the synchronization of action potential propagation along a bundle of neurons (ephaptic coupling) is considered. It is shown that this mechanism is similar to the salutatory conduction of the action potential between the nodes of Ranvier in myelinated axons. The proposed model allows us to estimate the scale of the correlation, i.e., the distance between neurons in the nervous tissue, wherein their synchronization becomes possible. The possibility for experimental verification of the proposed model of synchronization is discussed.

  2. Liénard-type models for the simulation of the action potential of cardiac nodal cells

    NASA Astrophysics Data System (ADS)

    Podziemski, P.; Żebrowski, J. J.

    2013-10-01

    Existing models of cardiac cells which include multi-variable cardiac transmembrane current are too complex to simulate the long time dynamical properties of the heart rhythm. The large number of parameters that need to be defined and set for such models make them not only cumbersome to use but also require a large computing power. Consequently, the application of such models for the bedside analysis of heart rate of a specific patient may be difficult. Other ways of modelling need to be investigated. We consider the general problem of developing a model of cardiac pacemaker tissue that allows to combine the investigation of phenomena at a time scale of thousands of heart beats with the ability to reproduce realistic tissue-level characteristics of cell dynamics. We propose a modified van der Pol-Duffing equation-a Liénard-type oscillator-as a phenomenological model for cardiac nodal tissue, with certain important physiological similarities to ion-channel models of cardiac pacemaker cells. The model presented here is specifically designed to qualitatively reproduce mesoscopic characteristics of cell dynamics, including action potential duration (APD) restitution properties, phase response characteristics, and phase space structure. We show that these characteristics agree qualitatively with the extensive ionic models and experimental results in the literature [Anumonwo et al., 1991, [33], Cao et al., 1999, [49], Coster and Celler, 2003, [31], Qu, 2004, [45], Tsalikakis et al., 2007, [32], Inada et al., 2009, [14], Qu et al., 2010, [50

  3. Hodgkin–Huxley revisited: reparametrization and identifiability analysis of the classic action potential model with approximate Bayesian methods

    PubMed Central

    Daly, Aidan C.; Holmes, Chris

    2015-01-01

    As cardiac cell models become increasingly complex, a correspondingly complex ‘genealogy’ of inherited parameter values has also emerged. The result has been the loss of a direct link between model parameters and experimental data, limiting both reproducibility and the ability to re-fit to new data. We examine the ability of approximate Bayesian computation (ABC) to infer parameter distributions in the seminal action potential model of Hodgkin and Huxley, for which an immediate and documented connection to experimental results exists. The ability of ABC to produce tight posteriors around the reported values for the gating rates of sodium and potassium ion channels validates the precision of this early work, while the highly variable posteriors around certain voltage dependency parameters suggests that voltage clamp experiments alone are insufficient to constrain the full model. Despite this, Hodgkin and Huxley's estimates are shown to be competitive with those produced by ABC, and the variable behaviour of posterior parametrized models under complex voltage protocols suggests that with additional data the model could be fully constrained. This work will provide the starting point for a full identifiability analysis of commonly used cardiac models, as well as a template for informative, data-driven parametrization of newly proposed models. PMID:27019736

  4. Hodgkin-Huxley revisited: reparametrization and identifiability analysis of the classic action potential model with approximate Bayesian methods.

    PubMed

    Daly, Aidan C; Gavaghan, David J; Holmes, Chris; Cooper, Jonathan

    2015-12-01

    As cardiac cell models become increasingly complex, a correspondingly complex 'genealogy' of inherited parameter values has also emerged. The result has been the loss of a direct link between model parameters and experimental data, limiting both reproducibility and the ability to re-fit to new data. We examine the ability of approximate Bayesian computation (ABC) to infer parameter distributions in the seminal action potential model of Hodgkin and Huxley, for which an immediate and documented connection to experimental results exists. The ability of ABC to produce tight posteriors around the reported values for the gating rates of sodium and potassium ion channels validates the precision of this early work, while the highly variable posteriors around certain voltage dependency parameters suggests that voltage clamp experiments alone are insufficient to constrain the full model. Despite this, Hodgkin and Huxley's estimates are shown to be competitive with those produced by ABC, and the variable behaviour of posterior parametrized models under complex voltage protocols suggests that with additional data the model could be fully constrained. This work will provide the starting point for a full identifiability analysis of commonly used cardiac models, as well as a template for informative, data-driven parametrization of newly proposed models. PMID:27019736

  5. An action potential-driven model of soleus muscle activation dynamics for locomotor-like movements

    NASA Astrophysics Data System (ADS)

    Kim, Hojeong; Sandercock, Thomas G.; Heckman, C. J.

    2015-08-01

    Objective. The goal of this study was to develop a physiologically plausible, computationally robust model for muscle activation dynamics (A(t)) under physiologically relevant excitation and movement. Approach. The interaction of excitation and movement on A(t) was investigated comparing the force production between a cat soleus muscle and its Hill-type model. For capturing A(t) under excitation and movement variation, a modular modeling framework was proposed comprising of three compartments: (1) spikes-to-[Ca2+]; (2) [Ca2+]-to-A; and (3) A-to-force transformation. The individual signal transformations were modeled based on physiological factors so that the parameter values could be separately determined for individual modules directly based on experimental data. Main results. The strong dependency of A(t) on excitation frequency and muscle length was found during both isometric and dynamically-moving contractions. The identified dependencies of A(t) under the static and dynamic conditions could be incorporated in the modular modeling framework by modulating the model parameters as a function of movement input. The new modeling approach was also applicable to cat soleus muscles producing waveforms independent of those used to set the model parameters. Significance. This study provides a modeling framework for spike-driven muscle responses during movement, that is suitable not only for insights into molecular mechanisms underlying muscle behaviors but also for large scale simulations.

  6. An action potential-driven model of soleus muscle activation dynamics for locomotor-like movements

    PubMed Central

    Kim, Hojeong; Sandercock, Thomas G.; Heckman, C. J.

    2016-01-01

    Objective The goal of this study was to develop a physiologically plausible, computationally robust model for the muscle activation dynamics (A(t)) under physiologically relevant excitation and movement. Approach The interaction of excitation and movement on A(t) was investigated comparing the force production between a cat soleus muscle and its Hill-type model. For capturing A(t) under excitation and movement variation, a modular modeling framework was proposed comprising of 3 compartments: (1) spikes-to-[Ca2+]; (2) [Ca2+]-to-A; and (3) A-to-force transformation. The individual signal transformations were modeled based on physiological factors so that the parameter values could be separately determined for individual modules directly based on experimental data. Main results The strong dependency of A(t) on excitation frequency and muscle length was found during both isometric and dynamically-moving contractions. The identified dependencies of A(t) under the static and dynamic conditions could be incorporated in the modular modeling framework by modulating the model parameters as a function of movement input. The new modeling approach was also applicable to cat soleus muscles producing waveforms independent of those used to set the model parameters. Significance This study provides a modeling framework for spike-driven muscle responses during movement, that is suitable not only for insights into molecular mechanisms underlying muscle behaviors but also for large scale simulations. PMID:26087477

  7. Mechanical surface waves accompany action potential propagation.

    PubMed

    El Hady, Ahmed; Machta, Benjamin B

    2015-01-01

    Many diverse studies have shown that a mechanical displacement of the axonal membrane accompanies the electrical pulse defining the action potential (AP). We present a model for these mechanical displacements as arising from the driving of surface wave modes in which potential energy is stored in elastic properties of the neuronal membrane and cytoskeleton while kinetic energy is carried by the axoplasmic fluid. In our model, these surface waves are driven by the travelling wave of electrical depolarization characterizing the AP, altering compressive electrostatic forces across the membrane. This driving leads to co-propagating mechanical displacements, which we term Action Waves (AWs). Our model allows us to estimate the shape of the AW that accompanies any travelling wave of voltage, making predictions that are in agreement with results from several experimental systems. Our model can serve as a framework for understanding the physical origins and possible functional roles of these AWs. PMID:25819404

  8. Mechanical surface waves accompany action potential propagation

    NASA Astrophysics Data System (ADS)

    El Hady, Ahmed; Machta, Benjamin B.

    2015-03-01

    Many diverse studies have shown that a mechanical displacement of the axonal membrane accompanies the electrical pulse defining the action potential (AP). We present a model for these mechanical displacements as arising from the driving of surface wave modes in which potential energy is stored in elastic properties of the neuronal membrane and cytoskeleton while kinetic energy is carried by the axoplasmic fluid. In our model, these surface waves are driven by the travelling wave of electrical depolarization characterizing the AP, altering compressive electrostatic forces across the membrane. This driving leads to co-propagating mechanical displacements, which we term Action Waves (AWs). Our model allows us to estimate the shape of the AW that accompanies any travelling wave of voltage, making predictions that are in agreement with results from several experimental systems. Our model can serve as a framework for understanding the physical origins and possible functional roles of these AWs.

  9. Modeling the effects of elevated temperatures on action potential propagation in unmyelinated axons

    NASA Astrophysics Data System (ADS)

    Ganguly, Mohit; Jenkins, Michael W.; Chiel, Hillel J.; Jansen, E. Duco

    2016-03-01

    Infrared lasers (λ=1.87 μm) are capable of inducing a thermally mediated nerve block in Aplysia and rat nerves. While this block is spatially precise and reversible in sensory and motor neurons, the mechanism of block is not clearly understood. Model predictions show that, at elevated temperatures, the rates of opening and closing of the voltage gated ion channels are disrupted and normal functioning of the gates is hindered. A model combining NEURON with Python is presented here that can simulate the behavior of unmyelinated nerve axons in the presence of spatially and temporally varying temperature distributions. Axon behavior and underlying mechanism leading to conduction block is investigated. The ability to understand the photothermal interaction of laser light and temperature dependence of membrane ion channels in-silico will help speed explorations of parameter space and guide future experiments testing the feasibility of selectively blocking pain conduction fibers (Photonic Analgesia of Nerves (PAIN)) in humans.

  10. Screening Action Potentials: The Power of Light

    PubMed Central

    Kaestner, Lars; Lipp, Peter

    2011-01-01

    Action potentials reflect the concerted activity of all electrogenic constituents in the plasma membrane during the excitation of a cell. Therefore, the action potential is an integrated read out and a promising parameter to detect electrophysiological failures or modifications thereof in diagnosis as well as in drug screens. Cellular action potentials can be recorded by optical approaches. To fulfill the pre-requirements to scale up for, e.g., pharmacological screens the following preparatory work has to be provided: (i) model cells under investigation need to represent target cells in the best possible manner; (ii) optical sensors that can be either small molecule dyes or genetically encoded potential probes need to provide a reliable read out with minimal interaction with the naive behavior of the cells and (iii) devices need to be capable to stimulate the cells, read out the signals with the appropriate speed as well as provide the capacity for a sufficient throughput. Here we discuss several scenarios for all three categories in the field of cardiac physiology and pharmacology and provide a perspective to use the power of light in screening cardiac action potentials. PMID:21847381

  11. An updated computational model of rabbit sinoatrial action potential to investigate the mechanisms of heart rate modulation

    PubMed Central

    Severi, Stefano; Fantini, Matteo; Charawi, Lara A; DiFrancesco, Dario

    2012-01-01

    The cellular basis of cardiac pacemaking is still debated. Reliable computational models of the sinoatrial node (SAN) action potential (AP) may help gain a deeper understanding of the phenomenon. Recently, novel models incorporating detailed Ca2+-handling dynamics have been proposed, but they fail to reproduce a number of experimental data, and more specifically effects of ‘funny’ (If) current modifications. We therefore developed a SAN AP model, based on available experimental data, in an attempt to reproduce physiological and pharmacological heart rate modulation. Cell compartmentalization and intracellular Ca2+-handling mechanisms were formulated as in the Maltsev–Lakatta model, focusing on Ca2+-cycling processes. Membrane current equations were revised on the basis of published experimental data. Modifications of the formulation of currents/pumps/exchangers to simulate If blockers, autonomic modulators and Ca2+-dependent mechanisms (ivabradine, caesium, acetylcholine, isoprenaline, BAPTA) were derived from experimental data. The model generates AP waveforms typical of rabbit SAN cells, whose parameters fall within the experimental ranges: 352 ms cycle length, 80 mV AP amplitude, −58 mV maximum diastolic potential (MDP), 108 ms APD50, and 7.1 V s−1 maximum upstroke velocity. Rate modulation by If-blocking drugs agrees with experimental findings: 20% and 22% caesium-induced (5 mm) and ivabradine-induced (3 μm) rate reductions, respectively, due to changes in diastolic depolarization (DD) slope, with no changes in either MDP or take-off potential (TOP). The model consistently reproduces the effects of autonomic modulation: 20% rate decrease with 10 nm acetylcholine and 28% increase with 1 μm isoprenaline, again entirely due to increase in the DD slope, with no changes in either MDP or TOP. Model testing of BAPTA effects showed slowing of rate, −26%, without cessation of beating. Our up-to-date model describes satisfactorily experimental data

  12. Role of CaMKII in RyR Leak, EC Coupling and Action Potential Duration: A Computational Model

    PubMed Central

    Hashambhoy, Yasmin L.; Greenstein, Joseph L.; Winslow, Raimond L.

    2010-01-01

    During heart failure, the ability of the sarcoplasmic reticulum (SR) to store Ca2+ is severely impaired resulting in abnormal Ca2+ cycling and excitation-contraction (EC) coupling. Recently, it has been proposed that “leaky” ryanodine receptors (RyRs) contribute to diminished Ca2+ levels in the SR. Various groups have experimentally investigated the effects of RyR phosphorylation mediated by Ca2+/calmodulin-dependent kinase II (CaMKII) on RyR behavior. Some of these results are difficult to interpret since RyR gating is modulated by many external proteins and ions, including Ca2+. Here, we present a mathematical model representing CaMKII-RyR interaction in the canine ventricular myocyte. This is an extension of our previous model which characterized CaMKII phosphorylation of L-type Ca2+ channels (LCCs) in the cardiac dyad. In this model, it is assumed that upon phosphorylation, RyR Ca2+-sensitivity is increased. Individual RyR phosphorylation is modeled as a function of dyadic CaMKII activity, which is modulated by local Ca2+ levels. The model is constrained by experimental measurements of Ca2+ spark frequency and steady state RyR phosphorylation. It replicates steady state RyR (leak) fluxes in the range measured in experiments without the addition of a separate passive leak pathway. Simulation results suggest that under physiological conditions, CaMKII phosphorylation of LCCs ultimately has a greater effect on RyR flux as compared with RyR phosphorylation. We also show that phosphorylation of LCCs decreases EC coupling gain significantly and increases action potential duration. These results suggest that LCC phosphorylation sites may be a more effective target than RyR sites in modulating diastolic RyR flux. PMID:20655925

  13. Therapeutic potential and mechanism of thymol action against ethanol-induced gastric mucosal injury in rat model.

    PubMed

    Chauhan, Anil Kumar; Kang, Sun Chul

    2015-11-01

    In this study, we investigated the potential of thymol and its mode of action to protect against the gastric mucosal injury induced by ethanol consumption in an in vivo model. Moreover, we determined the role of thymol in regulation of matrix metalloproteinase-9 (MMP-9), an enzyme belonging to the metalloproteinase group, which is responsible for the remodeling of injured tissues. Sprague-Dawley rats pretreated with thymol (10 mg/kg body weight) or normal saline were subjected to intragastric administration of 95% ethanol (5 mL/kg body weight). Morphological examination included ulcer index as a measurement of hemorrhages, and hematoxylin and eosin (H&E) staining was performed to analyze severity of gastric mucosal damage. Gelatinase zymography of tissue extract and in situ zymography were performed to demonstrate MMP-9 activity. Results of macroscopic examination suggested that thymol significantly protected gastric mucosa from damage induced by alcohol, which was severe in the case of alcohol-only treatment. H&E data demonstrated necrosis of the corpus region in alcohol-treated rats, which was abrogated in rats pretreated with thymol. Further, thymol protected against the constriction of small arteries and neutrophil infiltration in lymphatic vessels. Expression of antioxidant enzymes increased in the thymol-pretreated group, and downregulation of MMP-9 protein expression was observed by gelatin zymography as well as in situ zymography. The results of this study suggest that thymol protects against gastric mucosa injury induced by ethanol consumption by upregulating the secretion of antioxidant enzymes and downregulating the expression of the MMP-9 protein. PMID:26493110

  14. Potential hazards to embryo implantation: A human endometrial in vitro model to identify unwanted antigestagenic actions of chemicals

    SciTech Connect

    Fischer, L.; Deppert, W.R.; Pfeifer, D.; Stanzel, S.; Weimer, M.; Hanjalic-Beck, A.; Stein, A.; Straßer, M.; Zahradnik, H.P.; Schaefer, W.R.

    2012-05-01

    Embryo implantation is a crucial step in human reproduction and depends on the timely development of a receptive endometrium. The human endometrium is unique among adult tissues due to its dynamic alterations during each menstrual cycle. It hosts the implantation process which is governed by progesterone, whereas 17β-estradiol regulates the preceding proliferation of the endometrium. The receptors for both steroids are targets for drugs and endocrine disrupting chemicals. Chemicals with unwanted antigestagenic actions are potentially hazardous to embryo implantation since many pharmaceutical antiprogestins adversely affect endometrial receptivity. This risk can be addressed by human tissue-specific in vitro assays. As working basis we compiled data on chemicals interacting with the PR. In our experimental work, we developed a flexible in vitro model based on human endometrial Ishikawa cells. Effects of antiprogestin compounds on pre-selected target genes were characterized by sigmoidal concentration–response curves obtained by RT-qPCR. The estrogen sulfotransferase (SULT1E1) was identified as the most responsive target gene by microarray analysis. The agonistic effect of progesterone on SULT1E1 mRNA was concentration-dependently antagonized by RU486 (mifepristone) and ZK137316 and, with lower potency, by 4-nonylphenol, bisphenol A and apigenin. The negative control methyl acetoacetate showed no effect. The effects of progesterone and RU486 were confirmed on the protein level by Western blotting. We demonstrated proof of principle that our Ishikawa model is suitable to study quantitatively effects of antiprogestin-like chemicals on endometrial target genes in comparison to pharmaceutical reference compounds. This test is useful for hazard identification and may contribute to reduce animal studies. -- Highlights: ► We compare progesterone receptor-mediated endometrial effects of chemicals and drugs. ► 4-Nonylphenol, bisphenol A and apigenin exert weak

  15. Ribavirin Potentiates Interferon Action by Augmenting Interferon-Stimulated Gene Induction in Hepatitis C Virus Cell Culture Models

    PubMed Central

    Thomas, Emmanuel; Feld, Jordan J.; Li, Qisheng; Hu, Zongyi; Fried, Michael W.; Liang, T. Jake

    2012-01-01

    The combination of pegylated interferon (PEG-IFN) and ribavirin is the standard treatment for chronic hepatitis C. Our recent clinical study suggests that ribavirin augments the induction of interferon-stimulated genes (ISGs) in patients treated for hepatitis C virus (HCV) infection. In order to further characterize the mechanisms of action of ribavirin, we examined the effect of ribavirin treatment on ISG induction in cell culture. In addition, the effect of ribavirin on infectious HCV cell culture systems was studied. Similar to interferon (IFN)-α, ribavirin potently inhibits JFH-1 infection of Huh7.5.1 cells in a dose-dependent manner, which spans the physiological concentration of ribavirin in vivo. Microarray analysis and subsequent quantitative polymerase chain reaction assays demonstrated that ribavirin treatment resulted in the induction of a distinct set of ISGs. These ISGs, including IFN regulatory factors 7 and 9, are known to play an important role in anti-HCV responses. When ribavirin is used in conjunction with IFN-α, induction of specific ISGs is synergistic when compared with either drug applied separately. Direct up-regulation of these antiviral genes by ribavirin is mediated by a novel mechanism different from those associated with IFN signaling and intracellular double-stranded RNA sensing pathways such as RIG-I and MDA5. RNA interference studies excluded the activation of the Toll-like receptor and nuclear factor κB pathways in the action of ribavirin. Conclusion Our study suggests that ribavirin, acting by way of a novel innate mechanism, potentiates the anti-HCV effect of IFN. Understanding the mechanism of action of ribavirin would be valuable in identifying novel antivirals PMID:21254160

  16. Mechanical Surface Waves Accompany Action Potential Propagation

    NASA Astrophysics Data System (ADS)

    Machta, Benjamin; El Hady, Ahmed

    2015-03-01

    The action potential (AP) is the basic mechanism by which information is transmitted along neuronal axons. Although the excitable nature of axons is understood to be primarily electrical, many experimental studies have shown that a mechanical displacement of the axonal membrane co-propagates with the electrical signal. While the experimental evidence for co-propagating mechanical waves is diverse and compelling, there is no consensus for their physical underpinnings. We present a model in which these mechanical displacements arise from the driving of mechanical surface waves, in which potential energy is stored in elastic deformations of the neuronal membrane and cytoskeleton while kinetic energy is stored in the movement of the axoplasmic fluid. In our model these surface waves are driven by the traveling wave of electrical depolarization that characterizes the AP, altering the electrostatic forces across the membrane as it passes. Our model allows us to predict the shape of the displacement that should accompany any traveling wave of voltage, including the well-characterized AP. We expect our model to serve as a framework for understanding the physical origins and possible functional roles of these AWs in neurobiology. See Arxiv/1407.7600

  17. Impaired Action Potential Initiation in GABAergic Interneurons Causes Hyperexcitable Networks in an Epileptic Mouse Model Carrying a Human NaV1.1 Mutation

    PubMed Central

    Hedrich, Ulrike B.S.; Liautard, Camille; Kirschenbaum, Daniel; Pofahl, Martin; Lavigne, Jennifer; Liu, Yuanyuan; Theiss, Stephan; Slotta, Johannes; Escayg, Andrew; Dihné, Marcel; Beck, Heinz

    2014-01-01

    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 Ca2+ 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. PMID:25378155

  18. [Algorithm study on the three-dimensional cardiac tissue based on the model of ventricular action potential].

    PubMed

    Zhang, Hong; Ming, Lequn; Jin, Yinbin; Li, Mingjun; Zhang, Zhenxi; Lin, Yang

    2010-02-01

    Cardiac reentry is one of the important factors to induce arrhythmias. It could lead to ventricular tachycardia (VT) or even fibrillation (VF), resulting in sudden cardiac death. With the wide use of computer in the quantitative study of electrophysiology, the three-dimensional virtual heart for simulations needs to be developed imminently in computer. In this paper, numerical algorithm of the model was studied. The three-dimensional model was constructed by integrating Luo-Rudy 1991 ventricular cell model and diffusion equation. The operator splitting method was employed to solve the model. The alternate direction iterative (ADI) format and seven-point centered difference method were used for the partial differential equation. And the discrete format with second-order accuracy was taken for the boundary conditions. The results showed that the ADI format and seven-point centered difference method both could successfully figure out the membrane potential and electrical activities with good numerical stability. However, computing consumption could be greatly reduced with the ADI format, implying that the ADI method with large time step was more powerful in numerical simulations. PMID:20337013

  19. 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…

  20. Transferrin: structure, function and potential therapeutic actions.

    PubMed

    Gomme, Peter T; McCann, Karl B; Bertolini, Joseph

    2005-02-15

    There are many proteins that can multi-task. Transferrin, widely known as an iron-binding protein, is one such example of a multi-tasking protein. In this review, the multiple biological actions of transferrin, including its growth and cytoprotective activities, are discussed with the view of highlighting the potential therapeutic applications of this protein. PMID:15708745

  1. 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

  2. A combined method to estimate parameters of the thalamocortical model from a heavily noise-corrupted time series of action potential

    NASA Astrophysics Data System (ADS)

    Wang, Ruofan; Wang, Jiang; Deng, Bin; Liu, Chen; Wei, Xile; Tsang, K. M.; Chan, W. L.

    2014-03-01

    A combined method composing of the unscented Kalman filter (UKF) and the synchronization-based method is proposed for estimating electrophysiological variables and parameters of a thalamocortical (TC) neuron model, which is commonly used for studying Parkinson's disease for its relay role of connecting the basal ganglia and the cortex. In this work, we take into account the condition when only the time series of action potential with heavy noise are available. Numerical results demonstrate that not only this method can estimate model parameters from the extracted time series of action potential successfully but also the effect of its estimation is much better than the only use of the UKF or synchronization-based method, with a higher accuracy and a better robustness against noise, especially under the severe noise conditions. Considering the rather important role of TC neuron in the normal and pathological brain functions, the exploration of the method to estimate the critical parameters could have important implications for the study of its nonlinear dynamics and further treatment of Parkinson's disease.

  3. A combined method to estimate parameters of the thalamocortical model from a heavily noise-corrupted time series of action potential

    SciTech Connect

    Wang, Ruofan; Wang, Jiang; Deng, Bin Liu, Chen; Wei, Xile; Tsang, K. M.; Chan, W. L.

    2014-03-15

    A combined method composing of the unscented Kalman filter (UKF) and the synchronization-based method is proposed for estimating electrophysiological variables and parameters of a thalamocortical (TC) neuron model, which is commonly used for studying Parkinson's disease for its relay role of connecting the basal ganglia and the cortex. In this work, we take into account the condition when only the time series of action potential with heavy noise are available. Numerical results demonstrate that not only this method can estimate model parameters from the extracted time series of action potential successfully but also the effect of its estimation is much better than the only use of the UKF or synchronization-based method, with a higher accuracy and a better robustness against noise, especially under the severe noise conditions. Considering the rather important role of TC neuron in the normal and pathological brain functions, the exploration of the method to estimate the critical parameters could have important implications for the study of its nonlinear dynamics and further treatment of Parkinson's disease.

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

    PubMed

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

    1982-12-01

    Electrical membrane potentials, oscillations, and action potentials are observed in proteinoid microspheres impaled with (3 M KC1) 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. PMID:7162535

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

    NASA Astrophysics Data System (ADS)

    Przybylski, Aleksander T.; Stratten, Wilford P.; Syren, Robert M.; Fox, Sidney W.

    1982-12-01

    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.

  6. 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.

  7. Ca channel gating during cardiac action potentials.

    PubMed

    Mazzanti, M; DeFelice, L J

    1990-10-01

    How do Ca channels conduct Ca ions during the cardiac action potential? We attempt to answer this question by applying a two-microelectrode technique, previously used for Na and K currents, in which we record the patch current and the action potential at the same time (Mazzanti, M., and L. J. DeFelice. 1987. Biophys. J. 12:95-100, and 1988. Biophys. J. 54:1139-1148; Wellis, D., L. J. DeFelice, and M. Mazzanti. 1990. Biophys. J. 57:41-48). In this paper, we also compare the action currents obtained by the technique with the step-protocol currents obtained during standard voltage-clamp experiments. Individual Ca channels were measured in 10 mM Ca/1 Ba and 10 mM Ba. To describe part of our results, we use the nomenclature introduced by Hess, P., J. B. Lansman, and R. W. Tsien (1984. Nature (Lond.). 311:538-544). With Ba as the charge carrier, Ca channel kinetics convert rapidly from long to short open times as the patch voltage changes from 20 to -20 mV. This voltage-dependent conversion occurs during action potentials and in step-protocol experiments. With Ca as the charge carrier, the currents are brief at all voltages, and it is difficult to define either the number of channels in the patch or the conductance of the individual channels. Occasionally, however, Ca-conducting channels spontaneously convert to long-open-time kinetics (in Hess et al., 1984, notation, mode 2). When this happens, which is about once in every 100beats, there usually appears to be only one channel in the patch. In this rare configuration, the channel is open long enough to measure its conductance in 10 Ca/ 1 Ba. The value is 8-10 pS, which is about half the conductance in Ba. Because the long openings occur so infrequently with Ca as the charge carrier, they contribute negligibly to the average Ca current at any particular time during an action potential. However, the total number of Ca ions entering during these long openings may be significant when compared to the number entering by the

  8. Dual optical recordings for action potentials and calcium handling in induced pluripotent stem cell models of cardiac arrhythmias using genetically encoded fluorescent indicators.

    PubMed

    Song, LouJin; Awari, Daniel W; Han, Elizabeth Y; Uche-Anya, Eugenia; Park, Seon-Hye E; Yabe, Yoko A; Chung, Wendy K; Yazawa, Masayuki

    2015-05-01

    Reprogramming of human somatic cells to pluripotency has been used to investigate disease mechanisms and to identify potential therapeutics. However, the methods used for reprogramming, in vitro differentiation, and phenotyping are still complicated, expensive, and time-consuming. To address the limitations, we first optimized a protocol for reprogramming of human fibroblasts and keratinocytes into pluripotency using single lipofection and the episomal vectors in a 24-well plate format. This method allowed us to generate multiple lines of integration-free and feeder-free induced pluripotent stem cells (iPSCs) from seven patients with cardiac diseases and three controls. Second, we differentiated human iPSCs derived from patients with Timothy syndrome into cardiomyocytes using a monolayer differentiation method. We found that Timothy syndrome cardiomyocytes showed slower, irregular contractions and abnormal calcium handling compared with the controls. The results are consistent with previous reports using a retroviral method for reprogramming and an embryoid body-based method for cardiac differentiation. Third, we developed an efficient approach for recording the action potentials and calcium transients simultaneously in control and patient cardiomyocytes using genetically encoded fluorescent indicators, ArcLight and R-GECO1. The dual optical recordings enabled us to observe prolonged action potentials and abnormal calcium handling in Timothy syndrome cardiomyocytes. We confirmed that roscovitine rescued the phenotypes in Timothy syndrome cardiomyocytes and that these findings were consistent with previous studies using conventional electrophysiological recordings and calcium imaging with dyes. The approaches using our optimized methods and dual optical recordings will improve iPSC applicability for disease modeling to investigate mechanisms underlying cardiac arrhythmias and to test potential therapeutics. PMID:25769651

  9. The Contribution of Ionic Currents to Rate-Dependent Action Potential Duration and Pattern of Reentry in a Mathematical Model of Human Atrial Fibrillation

    PubMed Central

    Lee, Young-Seon; Hwang, Minki; Song, Jun-Seop; Li, Changyong; Joung, Boyoung; Sobie, Eric A.; Pak, Hui-Nam

    2016-01-01

    Persistent atrial fibrillation (PeAF) in humans is characterized by shortening of action potential duration (APD) and attenuation of APD rate-adaptation. However, the quantitative influences of particular ionic current alterations on rate-dependent APD changes, and effects on patterns of reentry in atrial tissue, have not been systematically investigated. Using mathematical models of human atrial cells and tissue and performing parameter sensitivity analysis, we evaluated the quantitative contributions to action potential (AP) shortening and APD rate-adaptation of ionic current remodeling seen with PeAF. Ionic remodeling in PeAF was simulated by reducing L-type Ca2+ channel current (ICaL), increasing inward rectifier K+ current (IK1) and modulating five other ionic currents. Parameter sensitivity analysis, which quantified how each ionic current influenced APD in control and PeAF conditions, identified interesting results, including a negative effect of Na+/Ca2+ exchange on APD only in the PeAF condition. At high pacing rate (2 Hz), electrical remodeling in IK1 alone accounts for the APD reduction of PeAF, but at slow pacing rate (0.5 Hz) both electrical remodeling in ICaL alone (-70%) and IK1 alone (+100%) contribute equally to the APD reduction. Furthermore, AP rate-adaptation was affected by IKur in control and by INaCa in the PeAF condition. In a 2D tissue model, a large reduction (-70%) of ICaL becomes a dominant factor leading to a stable spiral wave in PeAF. Our study provides a quantitative and unifying understanding of the roles of ionic current remodeling in determining rate-dependent APD changes at the cellular level and spatial reentry patterns in tissue. PMID:26964092

  10. Exploring action potential initiation in neurons exposed to DC electric fields through dynamical analysis of conductance-based model

    NASA Astrophysics Data System (ADS)

    Yi, Guo-Sheng; Wang, Jiang; Han, Chun-Xiao; Deng, Bin; Wei, Xi-Le; Jin, Qi-Tao

    2014-05-01

    Noninvasive direct current (DC) electric stimulation of central nervous system is today a promising therapeutic option to alleviate the symptoms of a number of neurological disorders. Despite widespread use of this noninvasive brain modulation technique, a generalizable explanation of its biophysical basis has not been described which seriously restricts its application and development. This paper investigated the dynamical behaviors of Hodgkin's three classes of neurons exposed to DC electric field based on a conductance-based neuron model. With phase plane and bifurcation analysis, the different responses of each class of neuron to the same stimulation are shown to derive from distinct spike initiating dynamics. Under the effects of negative DC electric field, class 1 neuron generates repetitive spike through a saddle-node on invariant circle (SNIC) bifurcation, while it ceases this repetitive behavior through a Hopf bifurcation; Class 2 neuron generates repetitive spike through a Hopf bifurcation, meanwhile it ceases this repetitive behavior also by a Hopf bifurcation; Class 3 neuron can generate single spike through a quasi-separatrix-crossing (QSC) at first, then it generates repetitive spike through a Hopf bifurcation, while it ceases this repetitive behavior through a SNIC bifurcation. Furthermore, three classes of neurons' spiking frequency f-electric field E (f-E) curves all have parabolic shape. Our results highlight the effects of external DC electric field on neuronal activity from the biophysical modeling point of view. It can contribute to the application and development of noninvasive DC brain modulation technique.

  11. Changes of blood flow, oxygen tension, action potential and vascular permeability induced by arterial ischemia or venous congestion on the spinal cord in canine model.

    PubMed

    Kobayashi, Shigeru; Yoshizawa, Hidezo; Shimada, Seiichiro; Guerrero, Alexander Rodríguez; Miyachi, Masaya

    2013-01-01

    It is generally considered that the genesis of myelopathy associated with the degenerative conditions of the spine may result from both mechanical compression and circulatory disturbance. Many references about spinal cord tissue ischemic damage can be found in the literature, but not detailed studies about spinal cord microvasculature damage related to congestion or blood permeability. This study investigates the effect of ischemia and congestion on the spinal cord using an in vivo model. The aorta was clamped as an ischemia model of the spinal cord and the inferior vena cava was clamped as a congestion model at the 6th costal level for 30 min using forceps transpleurally. Measurements of blood flow, partial oxygen pressure, and conduction velocity in the spinal cord were repeated over a period of 1 h after release of clamping. Finally, we examined the status of blood-spinal cord barrier under fluorescence and transmission electron microscope. Immediately after clamping of the inferior vena cava, the central venous pressure increased by about four times. Blood flow, oxygen tension and action potential were more severely affected by the aorta clamping; but this ischemic model did not show any changes of blood permeability in the spinal cord. The intramedullar edema was more easily produced by venous congestion than by arterial ischemia. In conclusions, venous congestion may be a preceding and essential factor of circulatory disturbance in the compressed spinal cord inducing myelopathy. PMID:22912247

  12. Action potential broadening in a presynaptic channelopathy.

    PubMed

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

    2016-01-01

    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 Ca(2+) influx and GABA release, and decreased spontaneous Purkinje cell firing. We find no evidence for developmental compensation for inherited Kv1.1 dysfunction. PMID:27381274

  13. Action potential broadening in a presynaptic channelopathy

    PubMed Central

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

    2016-01-01

    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. PMID:27381274

  14. 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.

  15. 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.…

  16. [Individualised medicine - potentials and need for action].

    PubMed

    Hüsing, Bärbel

    2010-01-01

    Individualised medicine aims to classify seemingly homogenous patient groups into smaller clinically relevant subgroups (stratification) in order to be able to treat them differently, thus contributing to the improvement of health care services, to the prevention of inappropriate treatments and to the reduction of adverse effects. This article summarises a report to the Office of Technology Assessment at the German Bundestag and points out the need for action for transferring individualised medicine from research to clinical application: significant incentives are required in order to prove the clinical validity of newly identified biomarkers of complex diseases. Sustainable business models for the joint development of new applications by research institutions, biotechnology companies, pharmaceuticals and medical devices companies are required. Instruments for transferring knowledge from bench to bedside (translational research) and the existing regulatory framework should be further developed in order to strike an appropriate balance between incentives for accelerating the transfer of innovative technology to the health care sector while, at the same time, ensuring patient safety, high quality and clinical utility. PMID:21147435

  17. Microcomputer program for automated action potential waveform analysis.

    PubMed

    Soto, E; Salceda, E; Cruz, R; Ortega, A; Vega, R

    2000-06-01

    A program for action potential waveform analysis based on a PC compatible computer is described. Single or averaged action potentials are analyzed by obtaining its first derivative and using criteria which allow automatic measurement of several action potential components, including: depolarization rate, repolarization rate, amplitude, duration, resting membrane potential and afterhyperpolarization amplitude and slope. Data can be imported from pClamp (Axon Instruments) and exported to other software such as Excel, Sigmaplot and MatLab for example. PMID:10764940

  18. Action potentials of curved nerves in finite limbs.

    PubMed

    Xiao, S; McGill, K C; Hentz, V R

    1995-06-01

    Previous simulations of volume-conducted nerve-fiber action-potentials have modeled the limb as semi-infinite or circularly cylindrical, and the fibers as straight lines parallel to the limb surface. The geometry of actual nerves and limbs, however, can be considerably more complicated. This paper presents a general method for computing the potentials of fibers with arbitrary paths in arbitrary finite limbs. It involves computing the propagating point-source response (PPSR), which is the potential arising from a single point source (dipole or tripole) travelling along the fiber. The PPSR can be applied to fibers of different conduction velocities by simple dilation or compression. The method is illustrated for oblique and spiralling nerve fibers. Potentials from oblique fibers are shown to be different for orthodromic and antidromic propagation. Such results show that the straight-line models are not always adequate for nerves with anatomical amounts of curvature. PMID:7790016

  19. Uncertainty Propagation in Nerve Impulses Through the Action Potential Mechanism.

    PubMed

    Torres Valderrama, Aldemar; Witteveen, Jeroen; Navarro, Maria; Blom, Joke

    2015-12-01

    We investigate the propagation of probabilistic uncertainty through the action potential mechanism in nerve cells. Using the Hodgkin-Huxley (H-H) model and Stochastic Collocation on Sparse Grids, we obtain an accurate probabilistic interpretation of the deterministic dynamics of the transmembrane potential and gating variables. Using Sobol indices, out of the 11 uncertain parameters in the H-H model, we unravel two main uncertainty sources, which account for more than 90 % of the fluctuations in neuronal responses, and have a direct biophysical interpretation. We discuss how this interesting feature of the H-H model allows one to reduce greatly the probabilistic degrees of freedom in uncertainty quantification analyses, saving CPU time in numerical simulations and opening possibilities for probabilistic generalisation of other deterministic models of great importance in physiology and mathematical neuroscience. PMID:26458902

  20. 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,…

  1. 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. PMID:25727465

  2. Dipole characterization of single neurons from their extracellular action potentials

    PubMed Central

    Victor, Jonathan D.

    2011-01-01

    The spatial variation of the extracellular action potentials (EAP) of a single neuron contains information about the size and location of the dominant current source of its action potential generator, which is typically in the vicinity of the soma. Using this dependence in reverse in a three-component realistic probe + brain + source model, we solved the inverse problem of characterizing the equivalent current source of an isolated neuron from the EAP data sampled by an extracellular probe at multiple independent recording locations. We used a dipole for the model source because there is extensive evidence it accurately captures the spatial roll-off of the EAP amplitude, and because, as we show, dipole localization, beyond a minimum cell-probe distance, is a more accurate alternative to approaches based on monopole source models. Dipole characterization is separable into a linear dipole moment optimization where the dipole location is fixed, and a second, nonlinear, global optimization of the source location. We solved the linear optimization on a discrete grid via the lead fields of the probe, which can be calculated for any realistic probe + brain model by the finite element method. The global source location was optimized by means of Tikhonov regularization that jointly minimizes model error and dipole size. The particular strategy chosen reflects the fact that the dipole model is used in the near field, in contrast to the typical prior applications of dipole models to EKG and EEG source analysis. We applied dipole localization to data collected with stepped tetrodes whose detailed geometry was measured via scanning electron microscopy. The optimal dipole could account for 96% of the power in the spatial variation of the EAP amplitude. Among various model error contributions to the residual, we address especially the error in probe geometry, and the extent to which it biases estimates of dipole parameters. This dipole characterization method can be applied to

  3. A web portal for in-silico action potential predictions

    PubMed Central

    Williams, Geoff; Mirams, Gary R.

    2015-01-01

    Introduction Multiple cardiac ion channels are prone to block by pharmaceutical compounds, and this can have large implications for cardiac safety. The effect of a compound on individual ion currents can now be measured in automated patch clamp screening assays. In-silico action potential models are proposed as one way of predicting the integrated compound effects on whole-cell electrophysiology, to provide an improved indication of pro-arrhythmic risk. Methods We have developed open source software to run cardiac electrophysiology simulations to predict the overall effect of compounds that block IKr, ICaL, INa, IKs, IK1 and Ito to varying degrees, using a choice of mathematical electrophysiology models. To enable safety pharmacology teams to run and evaluate these simulations easily, we have also developed an open source web portal interface to this simulator. Results The web portal can be found at https://chaste.cs.ox.ac.uk/ActionPotential. Users can enter details of compound affinities for ion channels in the form of IC50 or pIC50 values, run simulations, store the results for later retrieval, view summary graphs of the results, and export data to a spreadsheet format. Discussion This web portal provides a simple interface to reference versions of mathematical models, and well-tested state-of-the-art equation solvers. It provides safety teams easy access to the emerging technology of cardiac electrophysiology simulations for use in the drug-discovery process. PMID:25963830

  4. Metabolic syndrome potentiates the cardiac action potential-prolonging action of drugs: a possible 'anti-proarrhythmic' role for amlodipine.

    PubMed

    Caillier, Bertrand; Pilote, Sylvie; Patoine, Dany; Levac, Xavier; Couture, Christian; Daleau, Pascal; Simard, Chantale; Drolet, Benoit

    2012-03-01

    Type II diabetes was shown to prolong the QT interval on the ECG and to promote cardiac arrhythmias. This is not so clear for metabolic syndrome, a precursor state of type II diabetes. The objectives of the present study were to generate a guinea pig model of metabolic syndrome by long-term exposure to diabetogenic diets, and to evaluate the monophasic action potential duration (MAPD)-modulating effects of drugs in these animals. Male Hartley guinea pigs were fed with either the control, the High Fat High Sucrose (HFHS) or the High Fat High Fructose (HFHF) diet for 150 days. Evolution of weight, blood cholesterol, triglycerides, urea and glucose tolerance were regularly monitored. Histopathological evolution was also evaluated in target organs such as pancreas, heart, liver and kidneys. Ex vivo experiments using the Langendorff retroperfusion technique, isolated hearts from guinea pigs either fed with the control, the HFHS or the HFHF diet were exposed to dofetilide 20 nM (D), chromanol 293B 10 μM (C) and amlodipine 100 nM (A) in different drug combinations and monophasic action potential duration was measured at 90% repolarization (MAPD₉₀). Our data show that it is possible to generate a guinea pig model of metabolic syndrome by chronic exposure to diabetogenic diets. Minor histopathological abnormalities were observed, mainly in the pancreas and the liver. Metabolic syndrome potentiates the MAPD-prolonging actions of I(Kr)-blocking (dofetilide) and I(Ks)-blocking (chromanol 293B) drugs, an effect that is reversible upon administration of the calcium channel blocker amlodipine. PMID:22154802

  5. 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

  6. The effects of temperature on human compound action potentials.

    PubMed Central

    Bolton, C F; Sawa, G M; Carter, K

    1981-01-01

    The upper limbs of 10 healthy subjects were cooled and then warmed over physiological temperature ranges. The compound action potentials of median digital nerves, median sensory nerve at the wrist, radial sensory nerve at the wrist, and median thenar muscle, all showed progressive reduction in latency, amplitude, duration and area during rising temperature. Our studies suggest that the sensory compound action potential changes occur predominantly because of the summated effects of reduction in the duration of the action potentials of single myelinated fibres, although disproportionate increase in the conduction velocity of larger myelinated fibres also plays a role. Images PMID:7264687

  7. The bioelectrical source in computing single muscle fiber action potentials.

    PubMed Central

    van Veen, B K; Wolters, H; Wallinga, W; Rutten, W L; Boom, H B

    1993-01-01

    Generally, single muscle fiber action potentials (SFAPs) are modeled as a convolution of the bioelectrical source (being the transmembrane current) with a weighting or transfer function, representing the electrical volume conduction. In practice, the intracellular action potential (IAP) rather than the transmembrane current is often used as the source, because the IAP is relatively easy to obtain under experimental conditions. Using a core conductor assumption, the transmembrane current equals the second derivative of the IAP. In previous articles, discrepancies were found between experimental and simulated SFAPs. Adaptations in the volume conductor slightly altered the simulation results. Another origin of discrepancy might be an erroneous description of the source. Therefore, in the present article, different sources were studied. First, an analytical description of the IAP was used. Furthermore, an experimental IAP, a special experimental SFAP, and a measured transmembrane current scaled to our experimental situation were applied. The results for the experimental IAP were comparable to those with the analytical IAP. The best agreement between experimental and simulated data was found for a measured transmembrane current as source, but differences are still apparent. PMID:8324186

  8. Human action recognition using integrated model

    NASA Astrophysics Data System (ADS)

    Yi, Yang; Lin, Yikun

    2013-07-01

    A novel action recognition framework based on integrated model is proposed in the paper. First, the covariance descriptor is utilized to extract features from video sequences, and then each class specific codebook is constructed and appended to the global codebook. A static model applying the template matching technique and a dynamic model employing the trigram model are learned to capture complementary information in an action. And lastly, an integrated model is used to estimate the confidence of the static and dynamic models and produces a reliable result. Comparative experiments show that our presented method achieves superior results over other state-of-the-art approaches. Keywords: human action recognition, covariance descriptor, integrated model

  9. 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

  10. 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

  11. 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. PMID:26539072

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

    PubMed Central

    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. PMID:26539072

  13. Far-field potentials recorded from action potentials and from a tripole in a hemicylindrical volume.

    PubMed

    Jewett, D L; Deupree, D L

    1989-05-01

    There is growing evidence in support of the hypothesis that far-field potentials are recorded when action potentials encounter discontinuities in the surrounding volume. The present study found further support for this hypothesis using two methods of experimentation. The first method recorded potentials when the action potential from an isolated bullfrog sciatic nerve in a hemicylindrical volume (i) encountered a change in the shape of the surrounding volume, (ii) crossed a boundary between 2 volumes of differing resistivities, (iii) reached a bend in the nerve, or (iv) reached the functional end of the nerve. In the second method, potentials were recorded when an electrical tripole, constructed in a way to produce the electrical equivalent of an action potential, encountered the same discontinuities as well as when it was configured to simulate a curved nerve. These results are consistent with the hypothesis that dipole components of an action potential predominant in far-field recordings. PMID:2469568

  14. A neural network model of causative actions.

    PubMed

    Lee-Hand, Jeremy; Knott, Alistair

    2015-01-01

    A common idea in models of action representation is that actions are represented in terms of their perceptual effects (see e.g., Prinz, 1997; Hommel et al., 2001; Sahin et al., 2007; Umiltà et al., 2008; Hommel, 2013). In this paper we extend existing models of effect-based action representations to account for a novel distinction. Some actions bring about effects that are independent events in their own right: for instance, if John smashes a cup, he brings about the event of the cup smashing. Other actions do not bring about such effects. For instance, if John grabs a cup, this action does not cause the cup to "do" anything: a grab action has well-defined perceptual effects, but these are not registered by the perceptual system that detects independent events involving external objects in the world. In our model, effect-based actions are implemented in several distinct neural circuits, which are organized into a hierarchy based on the complexity of their associated perceptual effects. The circuit at the top of this hierarchy is responsible for actions that bring about independently perceivable events. This circuit receives input from the perceptual module that recognizes arbitrary events taking place in the world, and learns movements that reliably cause such events. We assess our model against existing experimental observations about effect-based motor representations, and make some novel experimental predictions. We also consider the possibility that the "causative actions" circuit in our model can be identified with a motor pathway reported in other work, specializing in "functional" actions on manipulable tools (Bub et al., 2008; Binkofski and Buxbaum, 2013). PMID:26175685

  15. 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

  16. 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. PMID:24465197

  17. 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.

  18. Propagation of Action Potentials: An Active Participation Exercise.

    ERIC Educational Resources Information Center

    Felsten, Gary

    1998-01-01

    Describes an active participation exercise that demonstrates the propagation of action potentials (the ability to transmit information through the neural network, dependent upon chemical interactions in the brain). Students assume the structure and function of the network by lining up around the room and communicating through hand signals and…

  19. 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…

  20. Awareness, Solidarity, and Action: An Educational Model

    ERIC Educational Resources Information Center

    Reichenbach, Michael R.

    2016-01-01

    How Extension fosters social change and innovation can be improved through the use of theory-based educational models. Educational models can serve as foundations for the conceptual designs of educational interventions. I describe, using examples from my own work, one such model: the awareness, solidarity, and action model. This three-part model…

  1. A neural network model of causative actions

    PubMed Central

    Lee-Hand, Jeremy; Knott, Alistair

    2015-01-01

    A common idea in models of action representation is that actions are represented in terms of their perceptual effects (see e.g., Prinz, 1997; Hommel et al., 2001; Sahin et al., 2007; Umiltà et al., 2008; Hommel, 2013). In this paper we extend existing models of effect-based action representations to account for a novel distinction. Some actions bring about effects that are independent events in their own right: for instance, if John smashes a cup, he brings about the event of the cup smashing. Other actions do not bring about such effects. For instance, if John grabs a cup, this action does not cause the cup to “do” anything: a grab action has well-defined perceptual effects, but these are not registered by the perceptual system that detects independent events involving external objects in the world. In our model, effect-based actions are implemented in several distinct neural circuits, which are organized into a hierarchy based on the complexity of their associated perceptual effects. The circuit at the top of this hierarchy is responsible for actions that bring about independently perceivable events. This circuit receives input from the perceptual module that recognizes arbitrary events taking place in the world, and learns movements that reliably cause such events. We assess our model against existing experimental observations about effect-based motor representations, and make some novel experimental predictions. We also consider the possibility that the “causative actions” circuit in our model can be identified with a motor pathway reported in other work, specializing in “functional” actions on manipulable tools (Bub et al., 2008; Binkofski and Buxbaum, 2013). PMID:26175685

  2. 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. PMID:5505231

  3. 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. PMID:21728204

  4. [Ion channels and action potentials in olfactory receptor cells].

    PubMed

    Kawai, Fusao; Miyachi, Ei-ichi

    2007-11-01

    The first step in olfactory sensation involves the binding of odorant molecules to specific receptor proteins on the ciliary surface of olfactory receptor cells (ORCs). Odorant receptors coupled to G-proteins activate adenylyl cyclase leading to the generation of cAMP, which directly gates a cyclic nucleotide-gated cationic channel in the ciliary membrane. This initial excitation causes a slow and graded depolarizing voltage change, which is encoded into a train of action potentials. Action potentials of ORCs are generated by voltage-gated Na- currents and T-type Ca2- currents in the somatic membrane. Isolated ORCs that have lost their cilia during the dissociation procedure are known to exhibit spike frequency accommodation by injecting the steady current. This raises the possibility that somatic ionic channels in ORCs may serve for odor adaptation at the level of spike encoding, although odor adaptation is mainly accomplished by the ciliary transduction machinery. This review discusses current knowledge concerning the mechanisms of spike generation in ORCs. It also reviews how neurotransmitters and hormones modulate ionic currents and action potentials in ORCs. PMID:18154041

  5. 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

  6. Action principles for extended magnetohydrodynamic models

    SciTech Connect

    Keramidas Charidakos, I.; Lingam, M.; Morrison, P. J.; White, R. L.; Wurm, A.

    2014-09-15

    The general, non-dissipative, two-fluid model in plasma physics is Hamiltonian, but this property is sometimes lost or obscured in the process of deriving simplified (or reduced) two-fluid or one-fluid models from the two-fluid equations of motion. To ensure that the reduced models are Hamiltonian, we start with the general two-fluid action functional, and make all the approximations, changes of variables, and expansions directly within the action context. The resulting equations are then mapped to the Eulerian fluid variables using a novel nonlocal Lagrange-Euler map. Using this method, we recover Lüst's general two-fluid model, extended magnetohydrodynamic (MHD), Hall MHD, and electron MHD from a unified framework. The variational formulation allows us to use Noether's theorem to derive conserved quantities for each symmetry of the action.

  7. 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

  8. Modeling the Male Reproductive Endocrine Axis: Potential Role for a Delay Mechanism in the Inhibitory Action of Gonadal Steroids on GnRH Pulse Frequency.

    PubMed

    Ferasyi, Teuku R; Barrett, P Hugh R; Blache, Dominique; Martin, Graeme B

    2016-05-01

    We developed a compartmental model so we could test mechanistic concepts in the control of the male reproductive endocrine axis. Using SAAM II computer software and a bank of experimental data from male sheep, we began by modeling GnRH-LH feed-forward and LH-T feedback. A key assumption was that the primary control signal comes from a hypothetical neural network (the PULSAR) that emits a digital (pulsatile) signal of variable frequency that drives GnRH secretion in square wave-like pulses. This model produced endocrine profiles that matched experimental observations for the testis-intact animal and for changes in GnRH pulse frequency after castration and T replacement. In the second stage of the model development, we introduced a delay in the negative feedback caused by the aromatization of T to estradiol at the brain level, a concept supported by empirical observations. The simulations showed how changes in the process of aromatization could affect the response of the pulsatile signal to inhibition by steroid feedback. The sensitivity of the PULSAR to estradiol was a critical factor, but the most striking observation was the effect of time delays. With longer delays, there was a reduction in the rate of aromatization and therefore a decrease in local estradiol concentrations, and the outcome was multiple-pulse events in the secretion of GnRH/LH, reflecting experimental observations. In conclusion, our model successfully emulates the GnRH-LH-T-GnRH loop, accommodates a pivotal role for central aromatization in negative feedback, and suggests that time delays in negative feedback are an important aspect of the control of GnRH pulse frequency. PMID:26910309

  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. PMID:24760928

  10. 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. PMID:23422156

  11. Reflective Internet Searching: An Action Research Model.

    ERIC Educational Resources Information Center

    Edwards, Sylvia Lauretta; Bruce, Christine

    2002-01-01

    Presents an action research model of planning, acting, recording, and reflecting as an approach to Internet searching. Explains how the constantly changing Internet environment requires continuous reassessment of search tools and strategies and development of new techniques. (Contains 14 references.) (SK)

  12. Modelling the control of interceptive actions.

    PubMed Central

    Beek, P J; Dessing, J C; Peper, C E; Bullock, D

    2003-01-01

    In recent years, several phenomenological dynamical models have been formulated that describe how perceptual variables are incorporated in the control of motor variables. We call these short-route models as they do not address how perception-action patterns might be constrained by the dynamical properties of the sensory, neural and musculoskeletal subsystems of the human action system. As an alternative, we advocate a long-route modelling approach in which the dynamics of these subsystems are explicitly addressed and integrated to reproduce interceptive actions. The approach is exemplified through a discussion of a recently developed model for interceptive actions consisting of a neural network architecture for the online generation of motor outflow commands, based on time-to-contact information and information about the relative positions and velocities of hand and ball. This network is shown to be consistent with both behavioural and neurophysiological data. Finally, some problems are discussed with regard to the question of how the motor outflow commands (i.e. the intended movement) might be modulated in view of the musculoskeletal dynamics. PMID:14561342

  13. Public Health Action Model for Cancer Survivorship

    PubMed Central

    Moore, Angela R.; Buchanan, Natasha D.; Fairley, Temeika L.; Smith, Judith Lee

    2016-01-01

    Long-term objectives associated with cancer survivors have been suggested by Healthy People 2020, including increasing the proportion of survivors living beyond 5 years after diagnosis and improving survivors’ mental and physical health-related quality of life. Prior to reaching these objectives, several intermediate steps must be taken to improve the physical, social, emotional, and financial well-being of cancer survivors. Public health has a role in developing strategic, actionable, and measurable approaches to facilitate change at multiple levels to improve the lives of survivors and their families. The social ecological model has been used by the public health community as the foundation of multilevel intervention design and implementation, encouraging researchers and practitioners to explore methods that promote internal and external changes at the individual, interpersonal, organizational, community, and policy levels. The survivorship community, including public health professionals, providers, policymakers, survivors, advocates, and caregivers, must work collaboratively to identify, develop, and implement interventions that benefit cancer survivors. The National Action Plan for Cancer Survivorship highlights public health domains and associated strategies that can be the impetus for collaboration between and among the levels in the social ecological model and are integral to improving survivor outcomes. This paper describes the Public Health Action Model for Cancer Survivorship, an integrative framework that combines the National Action Plan for Cancer Survivorship with the social ecological model to demonstrate how interaction among the various levels may promote better outcomes for survivors. PMID:26590641

  14. 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.

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

    SciTech Connect

    Zhang, Qing; Huang, Yong-Chang

    2011-11-01

    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 are consistent with quantum mechanics and classical physics. We deduce the Phantom, K-essence, Quintessence and Generalized Klein-Gordon Equation from the DBI model.

  16. 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.

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

    PubMed

    Chertoff, Mark; Lichtenhan, Jeffery; Willis, Marie

    2010-05-01

    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

  18. Model-based hierarchical reinforcement learning and human action control

    PubMed Central

    Botvinick, Matthew; Weinstein, Ari

    2014-01-01

    Recent work has reawakened interest in goal-directed or ‘model-based’ choice, where decisions are based on prospective evaluation of potential action outcomes. Concurrently, there has been growing attention to the role of hierarchy in decision-making and action control. We focus here on the intersection between these two areas of interest, considering the topic of hierarchical model-based control. To characterize this form of action control, we draw on the computational framework of hierarchical reinforcement learning, using this to interpret recent empirical findings. The resulting picture reveals how hierarchical model-based mechanisms might play a special and pivotal role in human decision-making, dramatically extending the scope and complexity of human behaviour. PMID:25267822

  19. Ontogeny of vestibular compound action potentials in the domestic chicken

    NASA Technical Reports Server (NTRS)

    Jones, S. M.; Jones, T. A.

    2000-01-01

    Compound action potentials of the vestibular nerve were measured from the surface of the scalp in 148 chickens (Gallus domesticus). Ages ranged from incubation day 18 (E18) to 22 days posthatch (P22). Responses were elicited using linear acceleration cranial pulses. Response thresholds decreased at an average rate of -0.45 dB/day. The decrease was best fit by an exponential model with half-maturity time constant of 5.1 days and asymptote of approximately -25.9 dB re:1.0 g/ms. Mean threshold approached within 3 dB of the asymptote by ages P6-P9. Similarly, response latencies decreased exponentially to within 3% of mature values at ages beyond P9. The half-maturity time constant for peripheral response peak latencies P1, N1, and P2 was comparable to thresholds and ranged from approximately 4.6 to 6.2 days, whereas central peaks (N2, P3, and N3) ranged from 2.9 to 3.4 days. Latency-intensity slopes for P1, N1, and P2 tended to decrease with age, reaching mature values within approximately 100 hours of hatching. Amplitudes increased as a function of age with average growth rates for response peaks ranging from 0.04 to 0.09 microV/day. There was no obvious asymptote to the growth of amplitudes over the ages studied. Amplitude-intensity slopes also increased modestly with age. The results show that gravity receptors are responsive to transient cranial stimuli as early as E19 in the chicken embryo. The functional response of gravity receptors continues to develop for many days after all major morphological structures are in place. Distinct maturational processes can be identified in central and peripheral neural relays. Functional improvements during maturation may result from refinements in the receptor epithelia, improvements in central and peripheral synaptic transmission, increased neural myelination, as well as changes in the mechanical coupling between the cranium and receptor organ.

  20. 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…

  1. Spectral action models of gravity on packed swiss cheese cosmology

    NASA Astrophysics Data System (ADS)

    Ball, Adam; Marcolli, Matilde

    2016-06-01

    We present a model of (modified) gravity on spacetimes with fractal structure based on packing of spheres, which are (Euclidean) variants of the packed swiss cheese cosmology models. As the action functional for gravity we consider the spectral action of noncommutative geometry, and we compute its expansion on a space obtained as an Apollonian packing of three-dimensional spheres inside a four-dimensional ball. Using information from the zeta function of the Dirac operator of the spectral triple, we compute the leading terms in the asymptotic expansion of the spectral action. They consist of a zeta regularization of the divergent sum of the leading terms of the spectral actions of the individual spheres in the packing. This accounts for the contribution of points 1 and 3 in the dimension spectrum (as in the case of a 3-sphere). There is an additional term coming from the residue at the additional point in the real dimension spectrum that corresponds to the packing constant, as well as a series of fluctuations coming from log-periodic oscillations, created by the points of the dimension spectrum that are off the real line. These terms detect the fractality of the residue set of the sphere packing. We show that the presence of fractality influences the shape of the slow-roll potential for inflation, obtained from the spectral action. We also discuss the effect of truncating the fractal structure at a certain scale related to the energy scale in the spectral action.

  2. The role of action effects in 12-month-olds' action control: a comparison of televised model and live model.

    PubMed

    Klein, Annette M; Hauf, Petra; Aschersleben, Gisa

    2006-12-01

    The present study investigated differences in infant imitation after watching a televised model and a live model and addressed the issue of whether action effects influence infants' action control in both cases. In a 2x2 design, 12-month-old infants observed a live or a televised model performing a three-step action sequence, in which either the 2nd or the 3rd action step was combined with an acoustical action effect. We assumed that infants would use the observed action-effect relations for their own action control in the test phase afterwards. Even though results exhibited differences in the absolute amount of imitation between the two demonstration groups, both groups showed similar result patterns regarding the action effect manipulation: infants imitated the action step that was followed by a salient action effect more often and mostly as the first target action, emphasizing the important role of action effects in infants' action control. PMID:17138306

  3. Dietary Exposure Potential Model

    EPA Science Inventory

    Existing food consumption and contaminant residue databases, typically products of nutrition and regulatory monitoring, contain useful information to characterize dietary intake of environmental chemicals. A PC-based model with resident database system, termed the Die...

  4. 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

  5. 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. PMID:27525414

  6. Preclinical models of antipsychotic drug action

    PubMed Central

    Moreno, José L.; González-Maeso, Javier

    2016-01-01

    One of the main obstacles faced by translational neuroscience is the development of animal models of psychiatric disorders. Behavioural pharmacology studies indicate that psychedelic drugs, such as lysergic acid diethylamide (LSD) and dissociative drugs, such as phencyclidine (PCP), induce in healthy human volunteers psychotic and cognitive symptoms that resemble some of those observed in schizophrenia patients. Serotonin 5-HT2A and metabotropic glutamate 2 receptors have been involved in the mechanism of action of psychedelic and dissociative drugs. Here we review recent advances using LSD-like and PCP-like drugs in rodent models that implicate these receptors in the neurobiology of schizophrenia and its treatment. PMID:23745738

  7. A Quantitative Description of the Relationship between the Area of Rabbit Ventricular Action Potentials and the Pattern of Stimulation

    PubMed Central

    Gibbs, C. L.; Johnson, E. A.; Tille, J.

    1963-01-01

    Intracellular microelectrodes were used to record action potentials from fibres of the isolated rabbit right ventricle and the areas of the action potentials were measured. The action potential area was found to depend in a reproducible way on the preceding pattern of stimulation. A mathematical model reproducing all the observed changes in the action potential area was developed. In the model the action potential area is taken as a linear function of the product of two time and stimulation dependent variables, M and N. The behaviour of each variable between action potentials is described by the solution of a second order differential equation. During each action potential the variables are assumed to change discontinuously, the magnitudes of the discontinuous changes being given by a set of subsidiary equations. It was found that the behaviour of all the fibres tested was described by the same set of equations, each single fibre being characterized by a set of ten independent constants. ImagesFigure 5 PMID:14070359

  8. Acute NMDA receptor antagonism disrupts synchronization of action potential firing in rat prefrontal cortex.

    PubMed

    Molina, Leonardo A; Skelin, Ivan; Gruber, Aaron J

    2014-01-01

    Antagonists of N-methyl-D-aspartate receptors (NMDAR) have psychotomimetic effects in humans and are used to model schizophrenia in animals. We used high-density electrophysiological recordings to assess the effects of acute systemic injection of an NMDAR antagonist (MK-801) on ensemble neural processing in the medial prefrontal cortex of freely moving rats. Although MK-801 increased neuron firing rates and the amplitude of gamma-frequency oscillations in field potentials, the synchronization of action potential firing decreased and spike trains became more Poisson-like. This disorganization of action potential firing following MK-801 administration is consistent with changes in simulated cortical networks as the functional connections among pyramidal neurons become less clustered. Such loss of functional heterogeneity of the cortical microcircuit may disrupt information processing dependent on spike timing or the activation of discrete cortical neural ensembles, and thereby contribute to hallucinations and other features of psychosis induced by NMDAR antagonists. PMID:24465743

  9. 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.

  10. Aldehydes: occurrence, carcinogenic potential, mechanism of action and risk assessment.

    PubMed

    Feron, V J; Til, H P; de Vrijer, F; Woutersen, R A; Cassee, F R; van Bladeren, P J

    1991-01-01

    Aldehydes constitute a group of relatively reactive organic compounds. They occur as natural (flavoring) constituents in a wide variety of foods and food components, often in relatively small, but occasionally in very large concentrations, and are also widely used as food additives. Evidence of carcinogenic potential in experimental animals is convincing for formaldehyde and acetaldehyde, limited for crotonaldehyde, furfural and glycidaldehyde, doubtful for malondialdehyde, very weak for acrolein and absent for vanillin. Formaldehyde carcinogenesis is a high-dose phenomenon in which the cytotoxicity plays a crucial role. Cytotoxicity may also be of major importance in acetaldehyde carcinogenesis but further studies are needed to prove or disprove this assumption. For a large number of aldehydes (relevant) data on neither carcinogenicity nor genotoxicity are available. From epidemiological studies there is no convincing evidence of aldehyde exposure being related to cancer in humans. Overall assessment of the cancer risk of aldehydes in the diet leads to the conclusion that formaldehyde, acrolein, citral and vanillin are no dietary risk factors, and that the opposite may be true for acetaldehyde, crotonaldehyde and furfural. Malondialdehyde, glycidaldehyde, benzaldehyde, cinnamaldehyde and anisaldehyde cannot be evaluated on the basis of the available data. A series of aldehydes should be subjected to at least mutagenicity, cytogenicity and cytotoxicity tests. Priority setting for testing should be based on expected mechanism of action and degree of human exposure. PMID:2017217

  11. Pharmacological actions of statins: potential utility in COPD.

    PubMed

    Young, R P; Hopkins, R; Eaton, T E

    2009-12-01

    Chronic obstructive pulmonary disease (COPD) is characterised by minimally reversible airflow limitation and features of systemic inflammation. Current therapies for COPD have been shown to reduce symptoms and infective exacerbations and to improve quality of life. However, these drugs have little effect on the natural history of the disease (progressive decline in lung function and exercise tolerance) and do not improve mortality. The anti-inflammatory effects of statins on both pulmonary and systemic inflammation through inhibition of guanosine triphosphatase and nuclear factor-κB mediated activation of inflammatory and matrix remodelling pathways could have substantial benefits in patients with COPD due to the following. 1) Inhibition of cytokine production (tumour necrosis factor-α, interleukin (IL)-6 and IL-8) and neutrophil infiltration into the lung; 2) inhibition of the fibrotic activity in the lung leading to small airways fibrosis and irreversible airflow limitation; 3) antioxidant and anti-inflammatory (IL-6 mediated) effects on skeletal muscle; 4) reduced inflammatory response to pulmonary infection; and 5) inhibition of the development (or reversal) of epithelial-mesenchymal transition, a precursor event to lung cancer. This review examines the pleiotropic pharmacological action of statins which inhibit key inflammatory and remodelling pathways in COPD and concludes that statins have considerable potential as adjunct therapy in COPD. PMID:20956147

  12. Developing an Action Learning Design Model

    ERIC Educational Resources Information Center

    Bong, Hyeon-Cheol; Cho, Yonjoo; Kim, Hyung-Sook

    2014-01-01

    As the number of organizations implementing action learning increases, both successful and failed cases also increase in action learning practice in South Korea. Existing studies on action learning have listed key success factors of action learning at the program level or at the team level but have not paid sufficient attention to the program…

  13. The impact of synaptic conductance on action potential waveform: evoking realistic action potentials with a simulated synaptic conductance.

    PubMed

    Johnston, Jamie; Postlethwaite, Michael; Forsythe, Ian D

    2009-10-15

    Most current clamp studies trigger action potentials (APs) by step current injection through the recording electrode and assume that the resulting APs are essentially identical to those triggered by orthodromic synaptic inputs. However this assumption is not always valid, particularly when the synaptic conductance is of large magnitude and of close proximity to the axon initial segment. We addressed this question of similarity using the Calyx of Held/MNTB synapse; we compared APs evoked by long duration step current injections, short step current injections and orthodromic synaptic stimuli. Neither injected current protocol evoked APs that matched the evoked orthodromic AP waveform, showing differences in AP height, half-width and after-hyperpolarization. We postulated that this 'error' could arise from changes in the instantaneous conductance during the combined synaptic and AP waveforms, since the driving forces for the respective ionic currents are integrating and continually evolving over this time-course. We demonstrate that a simple Ohm's law manipulation of the EPSC waveform, which accounts for the evolving driving force on the synaptic conductance during the AP, produces waveforms that closely mimic those generated by physiological synaptic stimulation. This stimulation paradigm allows supra-threshold physiological stimulation (single stimuli or trains) without the variability caused by quantal fluctuation in transmitter release, and can be implemented without a specialised dynamic clamp system. Combined with pharmacological tools this method provides a reliable means to assess the physiological roles of postsynaptic ion channels without confounding affects from the presynaptic input. PMID:19560491

  14. Rate-dependent force, intracellular calcium, and action potential voltage alternans are modulated by sarcomere length and heart failure induced-remodeling of thin filament regulation in human heart failure: A myocyte modeling study.

    PubMed

    Zile, Melanie A; Trayanova, Natalia A

    2016-01-01

    Microvolt T-wave alternans (MTWA) testing identifies heart failure patients at risk for lethal ventricular arrhythmias at near-resting heart rates (<110 beats per minute). Since pressure alternans occurs simultaneously with MTWA and has a higher signal to noise ratio, it may be a better predictor of arrhythmia, although the mechanism remains unknown. Therefore, we investigated the relationship between force alternans (FORCE-ALT), the cellular manifestation of pressure alternans, and action potential voltage alternans (APV-ALT), the cellular driver of MTWA. Our goal was to uncover the mechanisms linking APV-ALT and FORCE-ALT in failing human myocytes and to investigate how the link between those alternans was affected by pacing rate and by physiological conditions such as sarcomere length and heart failure induced-remodeling of mechanical parameters. To achieve this, a mechanically-based, strongly coupled human electromechanical myocyte model was constructed. Reducing the sarcoplasmic reticulum calcium uptake current (Iup) to 27% was incorporated to simulate abnormal calcium handling in human heart failure. Mechanical remodeling was incorporated to simulate altered thin filament activation and crossbridge (XB) cycling rates. A dynamical pacing protocol was used to investigate the development of intracellular calcium concentration ([Ca]i), voltage, and active force alternans at different pacing rates. FORCE-ALT only occurred in simulations incorporating reduced Iup, demonstrating that alternans in the intracellular calcium concentration (CA-ALT) induced FORCE-ALT. The magnitude of FORCE-ALT was found to be largest at clinically relevant pacing rates (<110 bpm), where APV-ALT was smallest. We found that the magnitudes of FORCE-ALT, CA-ALT and APV-ALT were altered by heart failure induced-remodeling of mechanical parameters and sarcomere length due to the presence of myofilament feedback. These findings provide important insight into the relationship between heart

  15. Development of an in vitro Hepatocyte Model to Investigate Chemical Mode of Action

    EPA Science Inventory

    There is a clear need to identify and characterize the potential of liver in vitro models that can be used to replace animals for mode of action analysis. Our goal is to use in vitro models for mode of action prediction which recapitulate critical cellular processes underlying in...

  16. Heart rate variability effect on the myocyte action potential duration restitution: insights from switched systems theory.

    PubMed

    Dvir, Hila; Zlochiver, Sharon

    2011-01-01

    The physiological heart rate presents a stochastic behavior known as heart rate variability (HRV). In this framework the influence of HRV on the action potential duration (APD) of the atrial myocyte is analyzed in a computer model. We have found that introducing HRV into the myocyte action potential model decreases the APD of the extra beat S2 in an S1-S2 protocol compared to constant heart rate. A possible theoretical explanation for this is also presented and is derived from switched systems theory. It is suggested to consider the myocyte action potential phase 4 and phase 2 as two operation modes of a switching system and analyze the stability of switching between them. Since random switching is known to have a stabilization effect on a switching system, this might explain why HRV has a stabilization effect on the myocyte APD restitution. Implications of this finding include reduced system stability for conditions with low HRV. A possible application for this phenomenon regards artificial pacemakers, where a preset added HRV is predicted to reduce susceptibility to arrhythmias. PMID:22254402

  17. Remedial action selection using groundwater modeling

    SciTech Connect

    Haddad, B.I.; Parish, G.B.; Hauge, L.

    1996-12-31

    An environmental investigation uncovered petroleum contamination at a gasoline station in southern Wisconsin. The site was located in part of the ancestral Rock River valley in Rock County, Wisconsin where the valley is filled with sands and gravels. Groundwater pump tests were conducted for determination of aquifer properties needed to plan a remediation system; the results were indicative of a very high hydraulic conductivity. The site hydrogeology was modeled using the U.S. Geological Survey`s groundwater model, Modflow. The calibrated model was used to determine the number, pumping rate, and configuration of recovery wells to remediate the site. The most effective configuration was three wells pumping at 303 liters per minute (1/m) (80 gallons per minute (gpm)), producing a total pumping rate of 908 l/m (240 gpm). Treating 908 l/min (240 gpm) or 1,308,240 liters per day (345,600 gallons per day) constituted a significant volume to be treated and discharged. It was estimated that pumping for the two year remediation would cost $375,000 while the air sparging would cost $200,000. The recommended remedial system consisted of eight air sparging wells and four vapor recovery laterals. The Wisconsin Department of Natural Resources (WDNR) approved the remedial action plan in March, 1993. After 11 months of effective operation the concentrations of removed VOCs had decreased by 94 percent and groundwater sampling indicated no detectable concentrations of gasoline contaminants. Groundwater modeling was an effective technique to determine the economic feasibility of a groundwater remedial alternative.

  18. A reconstruction of charge movement during the action potential in frog skeletal muscle.

    PubMed Central

    Huang, C. L.; Peachey, L. D.

    1992-01-01

    The transfer of intramembrane charge during an action potential at 4 degrees C was reconstructed for a model representing the electrical properties of frog skeletal muscle by a cylindrical surface membrane and 16 concentric annuli ("shells") of transverse tubular membrane of equal radial thickness. The lumina of the transverse tubules were separated from extracellular fluid by a fixed series resistance. The quantity, geometrical distribution and steady-state and kinetic properties of charge movement components were described by equations incorporating earlier experimental results. Introducing such nonlinear charge into the distributed model for muscle membrane diminished the maximum amplitude of the action potential within the transverse tubules by 2 mV but increased the maximum size of the after-depolarization by 3-5 mV and also its duration. However, these changes were small in comparison to the 135-mV deflection represented by the action potential. They therefore did not justify altering the values of the electrical parameters adopted by Adrian R.H., and L.D. Peachey (1973. J. Physiol. [Lond.]. 235:103-131.) and used in the present calculations. Cable properties significantly affected the time course and extent of charge movement in each shell during action potential propagation into the tubular system. Q beta charge moved relatively rapidly in all annuli, and did so without significant latency (approximately 0.3 ms) after the surface action potential upstroke. Its peak displacement varied between 53 and 58% (the range representing the difference fiber edge/fiber axis) of the total Q beta charge. This was attained at 5.4-7.3 ms after the stimulus, depending on depth within the tubules. In contrast, q gamma moved after a 1.7-2.9 ms latency and achieved a peak displacement of up to 22-34% of available charge. Both charge movement species could be driven by repetitive (47.7 Hz) action potentials without buildup of charge transfer. Such stimulus frequencies would

  19. Inflationary potentials in DBI models

    SciTech Connect

    Bessada, Dennis; Kinney, William H.; Tzirakis, Konstantinos E-mail: whkinney@buffalo.edu

    2009-09-01

    We study DBI inflation based upon a general model characterized by a power-law flow parameter ε(φ) ∝ φ{sup α} and speed of sound c{sub s}(φ) ∝ φ{sup β}, where α and β are constants. We show that in the slow-roll limit this general model gives rise to distinct inflationary classes according to the relation between α and β and to the time evolution of the inflaton field, each one corresponding to a specific potential; in particular, we find that the well-known canonical polynomial (large- and small-field), hybrid and exponential potentials also arise in this non-canonical model. We find that these non-canonical classes have the same physical features as their canonical analogs, except for the fact that the inflaton field evolves with varying speed of sound; also, we show that a broad class of canonical and D-brane inflation models are particular cases of this general non-canonical model. Next, we compare the predictions of large-field polynomial models with the current observational data, showing that models with low speed of sound have red-tilted scalar spectrum with low tensor-to-scalar ratio, in good agreement with the observed values. These models also show a correlation between large non-gaussianity with low tensor amplitudes, which is a distinct signature of DBI inflation with large-field polynomial potentials.

  20. Gifted Potential and Poverty: A Call for Extraordinary Action

    ERIC Educational Resources Information Center

    Kitano, Margie K.

    2003-01-01

    Dr. Robinson's proposed action plan will serve the needs of highly achieving gifted students. However, defining giftedness as high academic performance based on traditional assessment procedures could reverse the field's fledgling success in supporting culturally diverse gifted children and youth. Changing the focus of equity in gifted education…

  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. Scalar Potential Model of light

    NASA Astrophysics Data System (ADS)

    Hodge, John

    2008-04-01

    Some observations of light are inconsistent with a wave--like model. Other observations of light are inconsistent with a particle--like model. A model of light is proposed wherein Newton's and Democritus's speculations are combined with the cosmological scalar potential model (SPM). The SPM was tested by confrontation with observations of galaxy HI rotation curves (RCs), asymmetric RCs, redshift, discrete redshift, galaxy central mass, and central velocity dispersion; and with observations of the Pioneer Anomaly. The resulting model of light will be tested by numerical simulation of a photon behaving in a wave-like manner such as diffusion, interference, reflection, spectrography, and the Afshar experiment. Although the SPM light model requires more work, early results are beginning to emerge that suggest possible tests because a few predictions are inconsistent with both the current particle and wave models of light and that suggest a re-interpretation of the equations of quantum mechanics.

  3. Quantitative assessment of the distributions of membrane conductances involved in action potential backpropagation along basal dendrites.

    PubMed

    Acker, Corey D; Antic, Srdjan D

    2009-03-01

    Basal dendrites of prefrontal cortical neurons receive strong synaptic drive from recurrent excitatory synaptic inputs. Synaptic integration within basal dendrites is therefore likely to play an important role in cortical information processing. Both synaptic integration and synaptic plasticity depend crucially on dendritic membrane excitability and the backpropagation of action potentials. We carried out multisite voltage-sensitive dye imaging of membrane potential transients from thin basal branches of prefrontal cortical pyramidal neurons before and after application of channel blockers. We found that backpropagating action potentials (bAPs) are predominantly controlled by voltage-gated sodium and A-type potassium channels. In contrast, pharmacologically blocking the delayed rectifier potassium, voltage-gated calcium, or I(h) conductance had little effect on dendritic AP propagation. Optically recorded bAP waveforms were quantified and multicompartmental modeling was used to link the observed behavior with the underlying biophysical properties. The best-fit model included a nonuniform sodium channel distribution with decreasing conductance with distance from the soma, together with a nonuniform (increasing) A-type potassium conductance. AP amplitudes decline with distance in this model, but to a lesser extent than previously thought. We used this model to explore the mechanisms underlying two sets of published data involving high-frequency trains of APs and the local generation of sodium spikelets. We also explored the conditions under which I(A) down-regulation would produce branch strength potentiation in the proposed model. Finally, we discuss the hypothesis that a fraction of basal branches may have different membrane properties compared with sister branches in the same dendritic tree. PMID:19118105

  4. 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

  5. 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. PMID:25128573

  6. Experimental and theoretical description of higher order periods in cardiac tissue action potential duration

    NASA Astrophysics Data System (ADS)

    Herndon, Conner; Fenton, Flavio; Uzelac, Ilija

    Much theoretical, experimental, and clinical research has been devoted to investigating the initiation of cardiac arrhythmias by alternans, the first period doubling bifurcation in the duration of cardiac action potentials. Although period doubling above alternans has been shown to exist in many mammalian hearts, little is understood about their emergence or behavior. There currently exists no physiologically correct theory or model that adequately describes and predicts their emergence in stimulated tissue. In this talk we present experimental data of period 2, 4, and 8 dynamics and a mathematical model that describes these bifurcations. This model extends current cell models through the addition of memory and includes spatiotemporal nonlinearities arising from cellular coupling by tissue heterogeneity.

  7. On conviction's collective consequences: integrating moral conviction with the social identity model of collective action.

    PubMed

    van Zomeren, Martijn; Postmes, Tom; Spears, Russell

    2012-03-01

    This article examines whether and how moral convictions predict collective action to achieve social change. Because moral convictions - defined as strong and absolute stances on moral issues - tolerate no exceptions, any violation motivates individuals to actively change that situation. We propose that moral convictions have a special relationship with politicized identities and collective action because of the potentially strong normative fit between moral convictions and the action-oriented content of politicized identities. This effectively integrates moral conviction with the Social Identity Model of Collective Action (Van Zomeren, Postmes, & Spears, 2008), which predicts that, on the basis of a relevant social identity, group-based anger and efficacy predict collective action. Results from two studies indeed showed that moral convictions predicted collective action intentions (Study 1-2) and collective action (Study 2) through politicized identification, group-based anger, and group efficacy. We discuss theoretical and practical implications of our integrative model. PMID:22435846

  8. Alpha Ni optical model potentials

    NASA Astrophysics Data System (ADS)

    Billah, M. M.; Abdullah, M. N. A.; Das, S. K.; Uddin, M. A.; Basak, A. K.; Reichstein, I.; Sen Gupta, H. M.; Malik, F. B.

    2005-11-01

    The present work reports the analyses of the experimental differential cross-sections of α elastic scattering on 58,60,62,64Ni, over a wide range of incident energies, in terms of four types of optical potentials, namely shallow (molecular), deep non-monotonic, squared Woods-Saxon and semi-microscopic folding. All the four potentials produce a reasonable description of the experimental data. The potential parameters, calculated from the energy density functional theory using a realistic two-nucleon interaction, resemble closely the molecular potential parameters, which produce the best description of the experimental data for the four isotopes. The volume integrals and the energy variation of the parameters indicate the effect of the shell-model structure on the potentials. The folding potentials, without any need for renormalization, are found to describe reasonably well the elastic scattering cross-section data for the four isotopes within the energy range considered. In conformity with the previous observation on Ca isotopes, the number of nucleons, 4A=49, existing in α-like clusters in the target nucleus, is the same for the four isotopes, considered herein.

  9. MODELING WORLD BIOENERGY CROP POTENTIAL

    NASA Astrophysics Data System (ADS)

    Hagiwara, Kensuke; Hanasaki, Naota; Kanae, Shinjiro

    Bioenergy is regarded as clean energy due to its characteristics and expected to be a new support of world energy de¬mand, but there are few integrated assessments of the potential of bioenergy considering sustainable land use. We esti¬mated the global bioenergy potential with an integrated global water resources model, the H08. It can simulate the crop yields on global-scale at a spatial resolution of 0.50.5. Seven major crops in the world were considered; namely, maize, sugar beet, sugar cane, soybean, rapeseed, rice, and wheat, of which the first 5 are commonly used to produce biofuel now. Three different land-cover types were chosen as potential area for cultivation of biofuel-producing crop: fallow land, grassland, and portion of forests (excluding areas sensitive for biodiversity such as frontier forest). We attempted to estimate the maximum global bioenergy potential and it was estimated to be 1120EJ. Bioenergy potential depends on land-use limitations for the protection of bio-diversity and security of food. In another condition which assumed more land-use limitations, bioenergy potential was estimated to be 70-233EJ.

  10. Epidermal laser stimulation of action potentials in the frog sciatic nerve

    NASA Astrophysics Data System (ADS)

    Jindra, Nichole M.; Goddard, Douglas; Imholte, Michelle; Thomas, Robert J.

    2010-01-01

    Measurements of laser-stimulated action potentials in the sciatic nerve of leopard frogs (Rana pipiens) are made using two infrared lasers. The dorsal sides of the frog's hind limbs are exposed to short-pulsed 1540- and 1064-nm wavelengths at three separate spot sizes: 2, 3, and 4 mm. Energy density thresholds are determined for eliciting an action potential at each experimental condition. Results from these exposures show similar evoked potential thresholds for both wavelengths. The 2-mm-diam spot sizes yield action potentials at radiant exposure levels almost double that seen with larger beam sizes.

  11. Measurement Models for Reasoned Action Theory

    PubMed Central

    Hennessy, Michael; Bleakley, Amy; Fishbein, Martin

    2012-01-01

    Quantitative researchers distinguish between causal and effect indicators. What are the analytic problems when both types of measures are present in a quantitative reasoned action analysis? To answer this question, we use data from a longitudinal study to estimate the association between two constructs central to reasoned action theory: behavioral beliefs and attitudes toward the behavior. The belief items are causal indicators that define a latent variable index while the attitude items are effect indicators that reflect the operation of a latent variable scale. We identify the issues when effect and causal indicators are present in a single analysis and conclude that both types of indicators can be incorporated in the analysis of data based on the reasoned action approach. PMID:23243315

  12. Applications of Control Theory to the Dynamics and Propagation of Cardiac Action Potentials

    PubMed Central

    Muñoz, Laura M.; Stockton, Jonathan F.; Otani, Niels F.

    2011-01-01

    Sudden cardiac arrest is a widespread cause of death in the industrialized world. Most cases of sudden cardiac arrest are due to ventricular fibrillation (VF), a lethal cardiac arrhythmia. Electrophysiological abnormalities such as alternans (a beat-to-beat alternation in action potential duration) and conduction block have been suspected to contribute to the onset of VF. This study focuses on the use of control-systems techniques to analyze and design methods for suppressing these precursor factors. Control-systems tools, specifically controllability analysis and Lyapunov stability methods, were applied to a two-variable Karma model of the action-potential (AP) dynamics of a single cell, to analyze the effectiveness of strategies for suppressing AP abnormalities. State-feedback-integral (SFI) control was then applied to a Purkinje fiber simulated with the Karma model, where only one stimulating electrode was used to affect the system. SFI control converted both discordant alternans and 2:1 conduction block back toward more normal patterns, over a wider range of fiber lengths and pacing intervals compared with a Pyragas-type chaos controller. The advantages conferred by using feedback from multiple locations in the fiber, and using integral (i.e., memory) terms in the controller, are discussed. PMID:20407833

  13. Reconstruction of action potential of repolarization in patients with congenital long-QT syndrome

    NASA Astrophysics Data System (ADS)

    Kandori, Akihiko; Shimizu, Wataru; Yokokawa, Miki; Kamakura, Shiro; Miyatake, Kunio; Murakami, Masahiro; Miyashita, Tsuyoshi; Ogata, Kuniomi; Tsukada, Keiji

    2004-05-01

    A method for reconstructing an action potential during the repolarization period was developed. This method uses a current distribution—plotted as a current-arrow map (CAM)—calculated using magnetocardiogram (MCG) signals. The current arrows are summarized during the QRS complex period and subtracted during the ST-T wave period in order to reconstruct the action-potential waveform. To ensure the similarity between a real action potential and the reconstructed action potential using CAM, a monophasic action potential (MAP) and an MCG of the same patient with type-I long-QT syndrome were measured. Although the MAP had one notch that was associated with early afterdepolarization (EAD), the reconstructed action potential had two large and small notches. The small notch timing agreed with the occurrence of the EAD in the MAP. On the other hand, the initiation time of an abnormal current distribution coincides with the appearance timing of the first large notch, and its end time coincides with that of the second small notch. These results suggest that a simple reconstruction method using a CAM based on MCG data can provide a similar action-potential waveform to a MAP waveform without having to introduce a catheter.

  14. Simulation of the 3-state Potts model with chemical potential

    SciTech Connect

    Mercado, Ydalia Delgado; Gattringer, Christof; Evertz, Hans Gerd

    2011-05-23

    The 3-state Potts model with chemical potential is mapped to a flux representation where the complex action problem is resolved. We perform a Monte Carlo simulation based on a worm algorithm to study the phase diagram of the model. Our results shed light on the role which center symmetry and its breaking play for the QCD phase diagram.

  15. Mathematical simulations of ligand-gated and cell-type specific effects on the action potential of human atrium

    PubMed Central

    Maleckar, Mary M.; Greenstein, Joseph L.; Trayanova, Natalia A.; Giles, Wayne R.

    2010-01-01

    In the mammalian heart, myocytes and fibroblasts can communicate via gap junction, or connexin-mediated current flow. Some of the effects of this electrotonic coupling on the action potential waveform of the human ventricular myocyte have been analyzed in detail. The present study employs a recently developed mathematical model of the human atrial myocyte to investigate the consequences of this heterogeneous cell–cell interaction on the action potential of the human atrium. Two independent physiological processes which alter the physiology of the human atrium have been studied. i) The effects of the autonomic transmitter acetylcholine on the atrial action potential have been investigated by inclusion of a time-independent, acetylcholine-activated K+ current in this mathematical model of the atrial myocyte. ii) A non-selective cation current which is activated by natriuretic peptides has been incorporated into a previously published mathematical model of the cardiac fibroblast. These results identify subtle effects of acetylcholine, which arise from the nonlinear interactions between ionic currents in the human atrial myocyte. They also illustrate marked alterations in the action potential waveform arising from fibroblast–myocyte source–sink principles when the natriuretic peptide-mediated cation conductance is activated. Additional calculations also illustrate the effects of simultaneous activation of both of these cell-type specific conductances within the atrial myocardium. This study provides a basis for beginning to assess the utility of mathematical modeling in understanding detailed cell–cell interactions within the complex paracrine environment of the human atrial myocardium. PMID:19186188

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

    NASA Astrophysics Data System (ADS)

    Eickenscheidt, Max; Zeck, Günther

    2014-06-01

    Objective. 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. Approach. 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. Main results. 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. Significance. 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.

  17. Noncontact subnanometer measurement of transient surface displacement during action potential propagation

    NASA Astrophysics Data System (ADS)

    Akkin, Taner; Dave, Digant P.; Rylander, H. Grady, III; Milner, Thomas E.

    2005-04-01

    We have demonstrated non-contact, sub-nanometer optical measurement of neural surface displacement associated with action potential propagation without applying exogenous chemicals or reflection coatings. Signals recorded from crayfish leg nerve using a phase-sensitive optical low coherence reflectometer show that transient neural surface displacement due to action potential propagation is approximately 1 nm in amplitude and 1 ms in duration. Measured optical signals are coincident with electrical action potential arrival to the optical measurement site. Recent experiments indicate signals with similar amplitude and duration are observed in response to repetitive fast stimulation (200 stimuli/s).

  18. Developmental changes in the inward current of the action potential of Rohon-Beard neurones

    PubMed Central

    Baccaglini, Paola I.; Spitzer, Nicholas C.

    1977-01-01

    1. Rohon-Beard cells in the spinal cord of Xenopus tadpoles have been studied in animals from early neural tube to free-swimming larval stages. The onset and further development of electrical excitability of these neurones has been investigated in different ionic environments, to determine the ionic species carrying the inward current of the action potential. 2. The cells appear inexcitable at early stages (Nieuwkoop & Faber stages 18-20) and do not give action potentials to depolarizing current pulses. 3. The action potential is first recorded at stage 20. (A) The inward current is carried by Ca2+ at stages 20-25, since it is blocked by mm quantitites of La3+, Co2+ or Mn2+ and is unaffected by removal of Na+ or the addition of tetrodotoxin (TTX). (B) The action potential is an elevated plateau of long duration (mean 190 msec at stages 20-22). The duration decreases exponentially with repetitive stimulation. (C) The specific Ca2+ conductance (gCa) at the onset of the plateau of the action potential is 2·6 × 10-4 mho/cm2. Calculations show that a single action potential raises [Ca2+]1 by more than 100-fold. 4. At later times (stages 25-40), the inward current of the action potential is carried by both Na+ and Ca2+: the action potential has two components, an initial spike which is blocked by removal of Na+ or addition of TTX, followed by a plateau which is blocked by La3+, Co2+ or Mn2+. 5. Finally (stages 40-51), the inward current is primarily carried by Na+, since the action potential is blocked only by removal of Na+ or addition of TTX, and the overshoot agrees with the prediction of the Nernst equation for a Na-selective membrane. When the outward current channel is blocked and cells exposed to Na-free solutions, 67% of cells at the latest stages studied were incapable of producing action potentials in which the inward current is carried by divalent cations. 6. The duration of the action potential decreases from a maximum of about 1000 msec to about 1 msec

  19. Effect of Cardiac Tissue Anisotropy on Three-Dimensional Electrical Action Potential Propagation

    NASA Astrophysics Data System (ADS)

    He, Zhi Zhu; Liu, Jing

    A three-dimensional (3D) electrical action potential propagation model is developed to characterize the integrated effect of cardiac tissue structure using a homogenous function with a spatial inhomogeneity. This method may be more effective for bridging the gap between computational models and experimental data for cardiac tissue anisotropy. A generalized 3D eikonal relation considering anisotropy and a self-similar evolution solution of such a relation are derived to identify the effect of anisotropy and predict the anisotropy-induced electrical wave propagation instabilities. Furthermore, the phase field equation is introduced to obtain the complex three-dimensional numerical solution of the new correlation. The present results are expected to be valuable for better understanding the physiological behavior of cardiac tissues.

  20. Excitable Membranes and Action Potentials in Paramecia: An Analysis of the Electrophysiology of Ciliates.

    PubMed

    Schlaepfer, Charles H; Wessel, Ralf

    2015-01-01

    The ciliate Paramecium caudatum possesses an excitable cell membrane whose action potentials (APs) modulate the trajectory of the cell swimming through its freshwater environment. While many stimuli affect the membrane potential and trajectory, students can use current injection and extracellular ionic concentration changes to explore how APs cause reversal of the cell's motion. Students examine these stimuli through intracellular recordings, also gaining insight into the practices of electrophysiology. Paramecium's large size of around 150 µm, simple care, and relative ease to penetrate make them ideal model organisms for undergraduate students' laboratory study. The direct link between behavior and excitable membranes has thought provoking evolutionary implications for the study of paramecia. Recording from the cell, students note a small resting potential around -30 mV, differing from animal resting potentials. By manipulating ion concentrations, APs of the relatively long length of 20-30 ms up to several minutes with depolarizations maxing over 0 mV are observed. Through comparative analysis of membrane potentials and the APs induced by either calcium or barium, students can deduce the causative ions for the APs as well as the mechanisms of paramecium APs. Current injection allows students to calculate quantitative electric characteristics of the membrane. Analysis will follow the literature's conclusion in a V-Gated Ca(++) influx and depolarization resulting in feedback from intracellular Ca(++) that inactivates V-Gated Ca(++) channels and activates Ca-Dependent K(+) channels through a secondary messenger cascade that results in the K(+) efflux and repolarization. PMID:26557800

  1. 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

  2. Action potential detection by non-linear microscopy

    NASA Astrophysics Data System (ADS)

    Sacconi, Leonardo; Lotti, Jacopo; O'Connor, Rodney P.; Mapelli, Jonathan; Gandolfi, Daniela; D'Angelo, Egidio; Pavone, Francesco S.

    2009-02-01

    In this work, we combined the advantages of second-harmonic generation (SHG) with a random access (RA) excitation scheme to realize a new microscope (RA-SHG) capable of optically recording fast membrane potential events occurring in a wide-field configuration. The RA-SHG microscope in combination with a bulk staining method with FM4-64 was used to simultaneously record electrical activity from clusters of Purkinje cells (PCs) in acute cerebellar slices. Spontaneous electrical activity was also monitored simultaneously in pairs of neurons, where APs were recorded in a single trial without averaging. These results show the strength of this technique to describe the temporal dynamics of neuronal assemblies.

  3. Quantification of Transmembrane Currents during Action Potential Propagation in the Heart

    PubMed Central

    Gray, Richard A.; Mashburn, David N.; Sidorov, Veniamin Y.; Wikswo, John P.

    2013-01-01

    The measurement, quantitative analysis, theory, and mathematical modeling of transmembrane potential and currents have been an integral part of the field of electrophysiology since its inception. Biophysical modeling of action potential propagation begins with detailed ionic current models for a patch of membrane within a distributed cable model. Voltage-clamp techniques have revolutionized clinical electrophysiology via the characterization of the transmembrane current gating variables; however, this kinetic information alone is insufficient to accurately represent propagation. Other factors, including channel density, membrane area, surface/volume ratio, axial conductivities, etc., are also crucial determinants of transmembrane currents in multicellular tissue but are extremely difficult to measure. Here, we provide, to our knowledge, a novel analytical approach to compute transmembrane currents directly from experimental data, which involves high-temporal (200 kHz) recordings of intra- and extracellular potential with glass microelectrodes from the epicardial surface of isolated rabbit hearts during propagation. We show for the first time, to our knowledge, that during stable planar propagation the biphasic total transmembrane current (Im) dipole density during depolarization was ∼0.25 ms in duration and asymmetric in amplitude (peak outward current was ∼95 μA/cm2 and peak inward current was ∼140 μA/cm2), and the peak inward ionic current (Iion) during depolarization was ∼260 μA/cm2 with duration of ∼1.0 ms. Simulations of stable propagation using the ionic current versus transmembrane potential relationship fit from the experimental data reproduced these values better than traditional ionic models. During ventricular fibrillation, peak Im was decreased by 50% and peak Iion was decreased by 70%. Our results provide, to our knowledge, novel quantitative information that complements voltage- and patch-clamp data. PMID:23332079

  4. 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...

  5. 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...

  6. Uniform Action Potential Repolarization within the Sarcolemma of In Situ Ventricular Cardiomyocytes

    PubMed Central

    Bu, Guixue; Adams, Heather; Berbari, Edward J.; Rubart, Michael

    2009-01-01

    Previous studies have speculated, based on indirect evidence, that the action potential at the transverse (t)-tubules is longer than at the surface membrane in mammalian ventricular cardiomyocytes. To date, no technique has enabled recording of electrical activity selectively at the t-tubules to directly examine this hypothesis. We used confocal line-scan imaging in conjunction with the fast response voltage-sensitive dyes ANNINE-6 and ANNINE-6plus to resolve action potential-related changes in fractional dye fluorescence (ΔF/F) at the t-tubule and surface membranes of in situ mouse ventricular cardiomyocytes. Peak ΔF/F during action potential phase 0 depolarization averaged −21% for both dyes. The shape and time course of optical action potentials measured with the water-soluble ANNINE-6plus were indistinguishable from those of action potentials recorded with intracellular microelectrodes in the absence of the dye. In contrast, optical action potentials measured with the water-insoluble ANNINE-6 were significantly prolonged compared to the electrical recordings obtained from dye-free hearts, suggesting electrophysiological effects of ANNINE-6 and/or its solvents. With either dye, the kinetics of action potential-dependent changes in ΔF/F during repolarization were found to be similar at the t-tubular and surface membranes. This study provides what to our knowledge are the first direct measurements of t-tubule electrical activity in ventricular cardiomyocytes, which support the concept that action potential duration is uniform throughout the sarcolemma of individual cells. PMID:19289075

  7. Pharmacological actions and potential uses of Momordica charantia: a review.

    PubMed

    Grover, J K; Yadav, S P

    2004-07-01

    Since ancient times, plants and herbal preparations have been used as medicine. Research carried out in last few decades has certified several such claims of use of several plants of traditional medicine. Popularity of Momordica charantia (MC) in various systems of traditional medicine for several ailments (antidiabetic, abortifacient, anthelmintic, contraceptive, dysmenorrhea, eczema, emmenagogue, antimalarial, galactagogue, gout, jaundice, abdominal pain, kidney (stone), laxative, leprosy, leucorrhea, piles, pneumonia, psoriasis, purgative, rheumatism, fever and scabies) focused the investigator's attention on this plant. Over 100 studies using modern techniques have authenticated its use in diabetes and its complications (nephropathy, cataract, insulin resistance), as antibacterial as well as antiviral agent (including HIV infection), as anthelmintic and abortifacient. Traditionally it has also been used in treating peptic ulcers, interestingly in a recent experimental studies have exhibited its potential against Helicobacter pylori. Most importantly, the studies have shown its efficacy in various cancers (lymphoid leukemia, lymphoma, choriocarcinoma, melanoma, breast cancer, skin tumor, prostatic cancer, squamous carcinoma of tongue and larynx, human bladder carcinomas and Hodgkin's disease). There are few reports available on clinical use of MC in diabetes and cancer patients that have shown promising results. PMID:15182917

  8. Action potentials of embryonic dorsal root ganglion neurones in Xenopus tadpoles.

    PubMed Central

    Baccaglini, P I

    1978-01-01

    1. Several classes of action potentials can be distinguished in dorsal root ganglion cells, studied by intracellular recording techniques in Xenopus laevis tadpoles 4.5--51 days old. The ionic basis of the action potential was investigated by changing the ionic environment of the cells and applying various blocking agents. 2. The Ca2+-dependent action potential is a plateau of relatively long duration (mean 8.7 msec). It is unaffected by removal of Na+ but blocked by mM quantities of Co2+. It is present only in small cells. 3. Ca2+/Na+-dependent action potentials. Type I is a spike followed by a plateau or hump of different durations (mean 8.1 msec). The spike is selectively blocked by removal of Na+, leaving the plateau which is in turn blocked by Co2+. It is present in cells of small and intermediate size. Type II is a spike of short duration (mean 2.0 msec) with only an inflection on the falling phase. The spike is blocked by removal of Na+ and no other components can be elicited. The inflection is blocked by Co2+. It is present in cells of all sizes. Type III is similar to type I but is seen only in solutions in which the outward current is blocked. It was observed only very infrequently. 4. Na+-dependent action potentials. Type I a is a short duration spike (mean 1.1 msec). It is abolished by removal of Na+ or addition of tetrodotoxin (TTX), but largely unaffected by Co2+ or La3+. It is present in cells of all sizes. When the outward current channels are blocked and cells exposed to Na+-free solutions, all cells are capable of producing an action potential in which the inward current is carried by divalent cations. Type I b is a spike with a smooth, more slowly falling phase. It has the same pharmacological properties as type I a action potential and is present in cells of small size. 5. Na+-dependent action potentials. Type II is a spike with an inflection on the falling phase (mean duration 3.4 msec). It is prolonged by Co2+ and La3+. Removal of Na

  9. A continuous-time neural model for sequential action

    PubMed Central

    Kachergis, George; Wyatte, Dean; O'Reilly, Randall C.; de Kleijn, Roy; Hommel, Bernhard

    2014-01-01

    Action selection, planning and execution are continuous processes that evolve over time, responding to perceptual feedback as well as evolving top-down constraints. Existing models of routine sequential action (e.g. coffee- or pancake-making) generally fall into one of two classes: hierarchical models that include hand-built task representations, or heterarchical models that must learn to represent hierarchy via temporal context, but thus far lack goal-orientedness. We present a biologically motivated model of the latter class that, because it is situated in the Leabra neural architecture, affords an opportunity to include both unsupervised and goal-directed learning mechanisms. Moreover, we embed this neurocomputational model in the theoretical framework of the theory of event coding (TEC), which posits that actions and perceptions share a common representation with bidirectional associations between the two. Thus, in this view, not only does perception select actions (along with task context), but actions are also used to generate perceptions (i.e. intended effects). We propose a neural model that implements TEC to carry out sequential action control in hierarchically structured tasks such as coffee-making. Unlike traditional feedforward discrete-time neural network models, which use static percepts to generate static outputs, our biological model accepts continuous-time inputs and likewise generates non-stationary outputs, making short-timescale dynamic predictions. PMID:25267830

  10. A continuous-time neural model for sequential action.

    PubMed

    Kachergis, George; Wyatte, Dean; O'Reilly, Randall C; de Kleijn, Roy; Hommel, Bernhard

    2014-11-01

    Action selection, planning and execution are continuous processes that evolve over time, responding to perceptual feedback as well as evolving top-down constraints. Existing models of routine sequential action (e.g. coffee- or pancake-making) generally fall into one of two classes: hierarchical models that include hand-built task representations, or heterarchical models that must learn to represent hierarchy via temporal context, but thus far lack goal-orientedness. We present a biologically motivated model of the latter class that, because it is situated in the Leabra neural architecture, affords an opportunity to include both unsupervised and goal-directed learning mechanisms. Moreover, we embed this neurocomputational model in the theoretical framework of the theory of event coding (TEC), which posits that actions and perceptions share a common representation with bidirectional associations between the two. Thus, in this view, not only does perception select actions (along with task context), but actions are also used to generate perceptions (i.e. intended effects). We propose a neural model that implements TEC to carry out sequential action control in hierarchically structured tasks such as coffee-making. Unlike traditional feedforward discrete-time neural network models, which use static percepts to generate static outputs, our biological model accepts continuous-time inputs and likewise generates non-stationary outputs, making short-timescale dynamic predictions. PMID:25267830

  11. In-vitro characterization of a cochlear implant system for recording of evoked compound action potentials

    PubMed Central

    2012-01-01

    Background Modern cochlear implants have integrated recording systems for measuring electrically evoked compound action potentials of the auditory nerve. The characterization of such recording systems is important for establishing a reliable basis for the interpretation of signals acquired in vivo. In this study we investigated the characteristics of the recording system integrated into the MED-EL PULSARCI100 cochlear implant, especially its linearity and resolution, in order to develop a mathematical model describing the recording system. Methods In-vitro setup: The cochlear implant, including all attached electrodes, was fixed in a tank of physiologic saline solution. Sinusoidal signals of the same frequency but with different amplitudes were delivered via a signal generator for measuring and recording on a single electrode. Computer simulations: A basic mathematical model including the main elements of the recording system, i.e. amplification and digitalization stage, was developed. For this, digital output for sinusoidal input signals of different amplitudes were calculated using in-vitro recordings as reference. Results Using an averaging of 100 measurements the recording system behaved linearly down to approximately -60 dB of the input signal range. Using the same method, a system resolution of 10 μV was determined for sinusoidal signals. The simulation results were in very good agreement with the results obtained from in-vitro experiments. Conclusions The recording system implemented in the MED-EL PULSARCI100 cochlear implant for measuring the evoked compound action potential of the auditory nerve operates reliably. The developed mathematical model provides a good approximation of the recording system. PMID:22531599

  12. Inhibition Potentiates the Synchronizing Action of Electrical Synapses

    PubMed Central

    Pfeuty, Benjamin; Golomb, David; Mato, Germán; Hansel, David

    2007-01-01

    In vivo and in vitro experimental studies have found that blocking electrical interactions connecting GABAergic interneurons reduces oscillatory activity in the γ range in cortex. However, recent theoretical works have shown that the ability of electrical synapses to promote or impede synchrony, when alone, depends on their location on the dendritic tree of the neurons, the intrinsic properties of the neurons and the connectivity of the network. The goal of the present paper is to show that this versatility in the synchronizing ability of electrical synapses is greatly reduced when the neurons also interact via inhibition. To this end, we study a model network comprising two-compartment conductance-based neurons interacting with both types of synapses. We investigate the effect of electrical synapses on the dynamical state of the network as a function of the strength of the inhibition. We find that for weak inhibition, electrical synapses reinforce inhibition-generated synchrony only if they promote synchrony when they are alone. In contrast, when inhibition is sufficiently strong, electrical synapses improve synchrony even if when acting alone they would stabilize asynchronous firing. We clarify the mechanism underlying this cooperative interplay between electrical and inhibitory synapses. We show that it is relevant in two physiologically observed regimes: spike-to-spike synchrony, where neurons fire at almost every cycle of the population oscillations, and stochastic synchrony, where neurons fire irregularly and at a rate which is substantially lower than the frequency of the global population rhythm. PMID:18946530

  13. 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. PMID:25884360

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

    PubMed Central

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

    2010-01-01

    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 P17-19 rats, which had dendrites that averaged 60 µm in length and in short SC dendrites from P30-33 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 where 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 P17-19 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. PMID:19535592

  15. Modeling actions and operations to support mission preparation

    NASA Technical Reports Server (NTRS)

    Malin, Jane T.; Ryan, D. P.; Schreckenghost, D. L.

    1994-01-01

    This paper describes two linked technology development projects to support Space Shuttle ground operations personnel, both during mission preparation analysis and related analyses in missions. The Space Propulsion Robust Analysis Tool (SPRAT) will provide intelligent support and automation for mission analysis setup, interpretation, reporting and documentation. SPRAT models the actions taken by flight support personnel during mission preparation and uses this model to generate an action plan. CONFIG will provide intelligent automation for procedure analyses and failure impact analyses, by simulating the interactions between operations and systems with embedded failures. CONFIG models the actions taken by crew during space vehicle malfunctions and simulates how the planned action sequences in procedures affect a device model. Jointly the SPRAT and CONFIG projects provide an opportunity to investigate how the nature of a task affects the representation of actions, and to determine a more general action representation supporting a broad range of tasks. This paper describes the problems in representing actions for mission preparation and their relation to planning and scheduling.

  16. Neuronal adaptation involves rapid expansion of the action potential initiation site.

    PubMed

    Scott, Ricardo S; Henneberger, Christian; Padmashri, Ragunathan; Anders, Stefanie; Jensen, Thomas P; Rusakov, Dmitri A

    2014-01-01

    Action potential (AP) generation is the key to information-processing in the brain. Although APs are normally initiated in the axonal initial segment, developmental adaptation or prolonged network activity may alter the initiation site geometry thus affecting cell excitability. Here we find that hippocampal dentate granule cells adapt their spiking threshold to the kinetics of the ongoing dendrosomatic excitatory input by expanding the AP-initiation area away from the soma while also decelerating local axonal spikes. Dual-patch soma-axon recordings combined with axonal Na(+) and Ca(2+) imaging and biophysical modelling show that the underlying mechanism involves distance-dependent inactivation of axonal Na(+) channels due to somatic depolarization propagating into the axon. Thus, the ensuing changes in the AP-initiation zone and local AP propagation could provide activity-dependent control of cell excitability and spiking on a relatively rapid timescale. PMID:24851940

  17. Mechanism of Action and Clinical Potential of Fingolimod for the Treatment of Stroke

    PubMed Central

    Li, Wentao; Xu, Haoliang; Testai, Fernando D.

    2016-01-01

    Fingolimod (FTY720) is an orally bio-available immunomodulatory drug currently approved by the FDA for the treatment of multiple sclerosis. Currently, there is a significant interest in the potential benefits of FTY720 on stroke outcomes. FTY720 and the sphingolipid signaling pathway it modulates has a ubiquitous presence in the central nervous system and both rodent models and pilot clinical trials seem to indicate that the drug may improve overall functional recovery in different stroke subtypes. Although the precise mechanisms behind these beneficial effects are yet unclear, there is evidence that FTY720 has a role in regulating cerebrovascular responses, blood–brain barrier permeability, and cell survival in the event of cerebrovascular insult. In this article, we critically review the data obtained from the latest laboratory findings and clinical trials involving both ischemic and hemorrhagic stroke, and attempt to form a cohesive picture of FTY720’s mechanisms of action in stroke. PMID:27617002

  18. Neuronal adaptation involves rapid expansion of the action potential initiation site

    PubMed Central

    Scott, Ricardo S.; Henneberger, Christian; Padmashri, Ragunathan; Anders, Stefanie; Jensen, Thomas P.; Rusakov, Dmitri A.

    2014-01-01

    Action potential (AP) generation is the key to information-processing in the brain. Although APs are normally initiated in the axonal initial segment, developmental adaptation or prolonged network activity may alter the initiation site geometry thus affecting cell excitability. Here we find that hippocampal dentate granule cells adapt their spiking threshold to the kinetics of the ongoing dendrosomatic excitatory input by expanding the AP-initiation area away from the soma while also decelerating local axonal spikes. Dual-patch soma–axon recordings combined with axonal Na+ and Ca2+ imaging and biophysical modelling show that the underlying mechanism involves distance-dependent inactivation of axonal Na+ channels due to somatic depolarization propagating into the axon. Thus, the ensuing changes in the AP-initiation zone and local AP propagation could provide activity-dependent control of cell excitability and spiking on a relatively rapid timescale. PMID:24851940

  19. Mechanism of Action and Clinical Potential of Fingolimod for the Treatment of Stroke.

    PubMed

    Li, Wentao; Xu, Haoliang; Testai, Fernando D

    2016-01-01

    Fingolimod (FTY720) is an orally bio-available immunomodulatory drug currently approved by the FDA for the treatment of multiple sclerosis. Currently, there is a significant interest in the potential benefits of FTY720 on stroke outcomes. FTY720 and the sphingolipid signaling pathway it modulates has a ubiquitous presence in the central nervous system and both rodent models and pilot clinical trials seem to indicate that the drug may improve overall functional recovery in different stroke subtypes. Although the precise mechanisms behind these beneficial effects are yet unclear, there is evidence that FTY720 has a role in regulating cerebrovascular responses, blood-brain barrier permeability, and cell survival in the event of cerebrovascular insult. In this article, we critically review the data obtained from the latest laboratory findings and clinical trials involving both ischemic and hemorrhagic stroke, and attempt to form a cohesive picture of FTY720's mechanisms of action in stroke. PMID:27617002

  20. Anthropomorphizing the Mouse Cardiac Action Potential via a Novel Dynamic Clamp Method

    PubMed Central

    Ahrens-Nicklas, Rebecca C.; Christini, David J.

    2009-01-01

    Abstract Interspecies differences can limit the translational value of excitable cells isolated from model organisms. It can be difficult to extrapolate from a drug- or mutation-induced phenotype in mice to human pathophysiology because mouse and human cardiac electrodynamics differ greatly. We present a hybrid computational-experimental technique, the cell-type transforming clamp, which is designed to overcome such differences by using a calculated compensatory current to convert the macroscopic electrical behavior of an isolated cell into that of a different cell type. We demonstrate the technique's utility by evaluating drug arrhythmogenicity in murine cardiomyocytes that are transformed to behave like human myocytes. Whereas we use the cell-type transforming clamp in this work to convert between mouse and human electrodynamics, the technique could be adapted to convert between the action potential morphologies of any two cell types of interest. PMID:19917221

  1. Models of Reality: Shaping Thought and Action.

    ERIC Educational Resources Information Center

    Richardson, Jacques, Ed.

    The 21 essays in this two-part book provide conceptual and operational understanding of the nature of models as representations of reality and as tools for description, analysis, interpretation, and forecasting. Topic areas addressed in part 1 (concept) include: the nature of models; the earth as a system; the determination of form; some…

  2. Increased Event-Related Potentials and Alpha-, Beta-, and Gamma-Activity Associated with Intentional Actions

    PubMed Central

    Karch, Susanne; Loy, Fabian; Krause, Daniela; Schwarz, Sandra; Kiesewetter, Jan; Segmiller, Felix; Chrobok, Agnieszka I.; Keeser, Daniel; Pogarell, Oliver

    2016-01-01

    Objective: Internally guided actions are defined as being purposeful, self-generated and offering choices between alternatives. Intentional actions are essential to reach individual goals. In previous empirical studies, internally guided actions were predominantly related to functional responses in frontal and parietal areas. The aim of the present study was to distinguish event-related potentials and oscillatory responses of intentional actions and externally guided actions. In addition, we compared neurobiological findings of the decision which action to perform with those referring to the decision whether or not to perform an action. Methods: Twenty-eight subjects participated in adapted go/nogo paradigms, including a voluntary selection condition allowing participants to (1) freely decide whether to press the response button or (2) to decide whether they wanted to press the response button with the right index finger or the left index finger. Results: The reaction times were increased when participants freely decided whether and how they wanted to respond compared to the go condition. Intentional processes were associated with a fronto-centrally located N2 and P3 potential. N2 and P3 amplitudes were increased during intentional actions compared to instructed responses (go). In addition, increased activity in the alpha-, beta- and gamma-frequency range was shown during voluntary behavior rather than during externally guided responses. Conclusion: These results may indicate that an additional cognitive process is needed for intentional actions compared to instructed behavior. However, the neural responses were comparatively independent of the kind of decision that was made (1) decision which action to perform; (2) decision whether or not to perform an action). Significance: The study demonstrates the importance of fronto-central alpha-, beta-, and gamma oscillations for voluntary behavior. PMID:26834680

  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. A Model of Microevolution in Action.

    ERIC Educational Resources Information Center

    Welch, Larry A.

    1993-01-01

    Presents an activity to help students understand the precepts of the Hardy-Weinberg principle and simultaneously permit observation of a model of evolution through natural selection in a nonthreatening setting. (PR)

  5. 76 FR 21938 - Potential Environmental Impacts of the Proposed Runway 13 Extension and Associated Actions for...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-19

    ... Federal Aviation Administration Potential Environmental Impacts of the Proposed Runway 13 Extension and... Administration (FAA), Department of Transportation (DOT). ACTION: Notice of availability of a final EA and FONSI/ROD for the evaluation of the potential environmental impacts associated with the proposed Runway...

  6. The cytosolic calcium transient modulates the action potential of rat ventricular myocytes.

    PubMed Central

    duBell, W H; Boyett, M R; Spurgeon, H A; Talo, A; Stern, M D; Lakatta, E G

    1991-01-01

    1. The modulation of the action potential by the cytosolic Ca2+ (Cai2+) transient was studied in single isolated rat ventricular myocytes loaded with the acetoxymethyl ester form of the Ca(2+)-sensitive fluorescent dye Indo-1. Stimulation following rest and exposure to ryanodine were used to change the amount of Ca2+ released from the sarcoplasmic reticulum and thus the size of the Cai2+ transient. The Cai2+ transient was measured as the change, upon stimulation, in the ratio of Indo-1 fluorescence at 410 nm to that at 490 nm (410/490) and action potentials or membrane currents were recorded using patch-type microelectrodes. 2. When stimulation was initiated following rest, the magnitude of the Cai2+ transient decreased in a beat-dependent manner until a steady state was reached. The negative staircase in the Cai2+ transient was accompanied by a similar beat-dependent decrease in the duration of the action potential, manifested primarily as a gradual loss of the action potential plateau (approximately -45 mV). A slow terminal phase of repolarization of a few millivolts in amplitude was found to parallel the terminal decay of the Cai2+ transient. 3. The terminal portion of phase-plane loops of membrane potential (Vm) vs. Indo-1 ratio from all of the beats of a stimulus train followed a common linear trajectory even though the individual beats differed markedly in the duration and amplitude of the action potential and Cai2+ transient. 4. When the stimulation dependence of the Cai2+ transient was titrated away with submaximal exposure to ryanodine, the stimulation-dependent changes in the action potential plateau and terminal phase of repolarization were also eliminated. The same effect was noted in cells which, fortuitously, did not show a staircase in the Cai2+ transient following a period of rest. 5. When action potentials were triggered immediately following spontaneous release of Ca2+ from the sarcoplasmic reticulum, which results in a small depolarization at the

  7. A novel analysis of excitatory currents during an action potential from suprachiasmatic nucleus neurons

    PubMed Central

    2013-01-01

    A new application of the action potential (AP) voltage-clamp technique is described based on computational analysis. An experimentally recorded AP is digitized. The resulting Vi vs. ti data set is applied to mathematical models of the ionic conductances underlying excitability for the cell from which the AP was recorded to test model validity. The method is illustrated for APs from suprachiasmatic nucleus (SCN) neurons and the underlying tetrodotoxin-sensitive Na+ current, INa, and the Ca2+ current, ICa. Voltage-step recordings have been made for both components from SCN neurons (Jackson et al. 2004). The combination of voltage-step and AP clamp results provides richer constraints for mathematical models of voltage-gated ionic conductances than either set of results alone, in particular the voltage-step results. For SCN neurons the long-term goal of this work is a realistic mathematical model of the SCN AP in which the equations for INa and ICa obtained from this analysis will be a part. Moreover, the method described in this report is general. It can be applied to any excitable cell. PMID:24047903

  8. Born-Infeld Electrodynamics and Euler-Heisenberg Model:. Outstanding Examples of the Lack of Commutativity among Quantized Truncated Actions and Truncated Quantized Actions

    NASA Astrophysics Data System (ADS)

    Accioly, Antonio; Gaete, Patricio; Helaÿel-Neto, José A.

    We calculate the lowest-order corrections to the static potential for both the generalized Born-Infeld electrodynamics and an Euler-Heisenberg-like model, in the presence of a constant external magnetic field. Our analysis is carried out within the framework of the gauge-invariant but path-dependent variables formalism. The calculation reveals a long-range correction ((1)/(r5)-type) to the Coulomb potential for the generalized Born-Infeld electrodynamics. Interestingly enough, in the Euler-Heisenberg-like model, the static potential remains Coulombian. Therefore, contrary to popular belief, the quantized truncated action and the truncated quantized action do not commute at all.

  9. 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. PMID:26131127

  10. Effect of nanomaterials on the compound action potential of the shore crab, Carcinus maenas.

    PubMed

    Windeatt, Kirsten M; Handy, Richard D

    2013-06-01

    Little is known about the effects of manufactured nanomaterials on the function of nerves. The experiment aimed to test the effects of three different nanomaterials (1 mg l⁻¹ of TiO₂ NPs, Ag NPs or SWCNT) on the compound action potential of the shore crab (Carcinus maenas) compared with an appropriate bulk powder or metal salt control (bulk TiO₂ powder, AgNO₃ and carbon black respectively). In single action potential recordings, there were no effects of any of the nanomaterials on the peak amplitude, duration, rate of rise (depolarisation), or rate of decrease (repolarisation) of the compound action potential in crab saline, despite settling of each nanomaterial directly onto the nerve preparation. The ability of the crab nerve to be stimulated to tetanus was also unaffected by exposure to the nanomaterials compared with the appropriate bulk powder or metal salt control. Solvent controls with sodium dodecyl sulfate (SDS) also had no effect on action potentials. Overall, the study concludes that there were no effects of the materials at the concentrations tested on the compound action potential of the shore crab in physiological saline. PMID:22394242

  11. The role of inward Na(+)-Ca2+ exchange current in the ferret ventricular action potential.

    PubMed Central

    Janvier, N C; Harrison, S M; Boyett, M R

    1997-01-01

    1. Inward Na(+)-Ca2+ exchange current (iNaCa) was either blocked in ferret ventricular cells by replacing extracellular Na+ with Li+ or substantially reduced by the almost complete elimination of the Ca2+ transient by buffering intracellular Ca2+ with the acetoxymethyl ester form of BAPTA (BAPTA AM). 2. During square wave voltage clamp pulses to 0 mV, replacing extracellular Na+ with Li+ or buffering intracellular Ca2+ with BAPTA AM resulted in the loss of a transient inward current. This current was increased by the application of isoprenaline (expected to increase the underlying Ca2+ transient) and displayed the voltage-dependent characteristics of inward iNaCa. 3. Replacing extracellular Na+ with Li+ or buffering intracellular Ca2+ caused a significant shortening of the action potential (at -65 mV, 44 +/- 2% with Li+ and 20 +/- 2% with BAPTA AM). The shortening can be explained by changes in iNaCa. 4. The action potential clamp technique was used to measure the BAPTA-sensitive current (putative iNaCa) and the Ca2+ current (ica; measured using nifedipine) during the action potential. Under control conditions, the inward BAPTA-sensitive current makes approximately the same contribution as iCa during much of the action potential plateau. These results suggest an important role for inward iNaCa in the ferret ventricular action potential. PMID:9051574

  12. Excitable Membranes and Action Potentials in Paramecia: An Analysis of the Electrophysiology of Ciliates

    PubMed Central

    Schlaepfer, Charles H.; Wessel, Ralf

    2015-01-01

    The ciliate Paramecium caudatum possesses an excitable cell membrane whose action potentials (APs) modulate the trajectory of the cell swimming through its freshwater environment. While many stimuli affect the membrane potential and trajectory, students can use current injection and extracellular ionic concentration changes to explore how APs cause reversal of the cell’s motion. Students examine these stimuli through intracellular recordings, also gaining insight into the practices of electrophysiology. Paramecium’s large size of around 150 µm, simple care, and relative ease to penetrate make them ideal model organisms for undergraduate students’ laboratory study. The direct link between behavior and excitable membranes has thought provoking evolutionary implications for the study of paramecia. Recording from the cell, students note a small resting potential around −30 mV, differing from animal resting potentials. By manipulating ion concentrations, APs of the relatively long length of 20–30 ms up to several minutes with depolarizations maxing over 0 mV are observed. Through comparative analysis of membrane potentials and the APs induced by either calcium or barium, students can deduce the causative ions for the APs as well as the mechanisms of paramecium APs. Current injection allows students to calculate quantitative electric characteristics of the membrane. Analysis will follow the literature’s conclusion in a V-Gated Ca++ influx and depolarization resulting in feedback from intracellular Ca++ that inactivates V-Gated Ca++ channels and activates Ca-Dependent K+ channels through a secondary messenger cascade that results in the K+ efflux and repolarization. PMID:26557800

  13. Effective action for noncommutative Bianchi I model

    NASA Astrophysics Data System (ADS)

    Rosenbaum, M.; Vergara, J. D.; Minzoni, A. A.

    2013-06-01

    Quantum Mechanics, as a mini-superspace of Field Theory has been assumed to provide physically relevant information on quantum processes in Field Theory. In the case of Quantum Gravity this would imply using Cosmological models to investigate quantum processes at distances of the order of the Planck scale. However because of the Stone-von Neuman Theorem, it is well known that quantization of Cosmological models by the Wheeler-DeWitt procedure in the context of a Heisenberg-Weyl group with piecewise continuous parameters leads irremediably to a volume singularity. In order to avoid this information catastrophe it has been suggested recently the need to introduce in an effective theory of the quantization some form of reticulation in 3-space. On the other hand, since in the geometry of the General Relativistic formulation of Gravitation space can not be visualized as some underlying static manifold in which the physical system evolves, it would be interesting to investigate whether the effective reticulation which removes the singularity in such simple cosmologies as the Bianchi models has a dynamical origin manifested by a noncommutativity of the generators of the Heisenberg-Weyl algebra, as would be expected from an operational point of view at the Planck length scale.

  14. Effective action for noncommutative Bianchi I model

    SciTech Connect

    Rosenbaum, M.; Vergara, J. D.; Minzoni, A. A.

    2013-06-12

    Quantum Mechanics, as a mini-superspace of Field Theory has been assumed to provide physically relevant information on quantum processes in Field Theory. In the case of Quantum Gravity this would imply using Cosmological models to investigate quantum processes at distances of the order of the Planck scale. However because of the Stone-von Neuman Theorem, it is well known that quantization of Cosmological models by the Wheeler-DeWitt procedure in the context of a Heisenberg-Weyl group with piecewise continuous parameters leads irremediably to a volume singularity. In order to avoid this information catastrophe it has been suggested recently the need to introduce in an effective theory of the quantization some form of reticulation in 3-space. On the other hand, since in the geometry of the General Relativistic formulation of Gravitation space can not be visualized as some underlying static manifold in which the physical system evolves, it would be interesting to investigate whether the effective reticulation which removes the singularity in such simple cosmologies as the Bianchi models has a dynamical origin manifested by a noncommutativity of the generators of the Heisenberg-Weyl algebra, as would be expected from an operational point of view at the Planck length scale.

  15. Optical coherence tomography for detection of compound action potential in Xenopus Laevis sciatic nerve

    NASA Astrophysics Data System (ADS)

    Troiani, Francesca; Nikolic, Konstantin; Constandinou, Timothy G.

    2016-03-01

    Due to optical coherence tomography (OCT) high spatial and temporal resolution, this technique could be used to observe the quick changes in the refractive index that accompany action potential. In this study we explore the use of time domain Optical Coherence Tomography (TD-OCT) for real time action potential detection in ex vivo Xenopus Laevis sciatic nerve. TD-OCT is the easiest and less expensive OCT technique and, if successful in detecting real time action potential, it could be used for low cost monitoring devices. A theoretical investigation into the order of magnitude of the signals detected by a TD-OCT setup is provided by this work. A linear dependence between the refractive index and the intensity changes is observed and the minimum SNR for which the setup could work is found to be SNR = 2 x 104.

  16. Optical magnetic detection of single-neuron action potentials using NV-diamond

    NASA Astrophysics Data System (ADS)

    Turner, Matthew; Barry, John; Schloss, Jennifer; Glenn, David; Walsworth, Ron

    2016-05-01

    A key challenge for neuroscience is noninvasive, label-free sensing of action potential dynamics in whole organisms with single-neuron resolution. Here, we report a new approach to this problem: using nitrogen-vacancy (NV) color centers in diamond to measure the time-dependent magnetic fields produced by single-neuron action potentials. We demonstrate our method using excised single neurons from two invertebrate species, marine worm and squid; and then by single-neuron action potential magnetic sensing exterior to whole, live, opaque marine worms for extended periods with no adverse effect. The results lay the groundwork for real-time, noninvasive 3D magnetic mapping of functional mammalian neuronal networks.

  17. Action potentials induce uniform calcium influx in mammalian myelinated optic nerves.

    PubMed

    Zhang, Chuan-Li; Wilson, J Adam; Williams, Justin; Chiu, Shing Yan

    2006-08-01

    The myelin sheath enables saltatory conduction by demarcating the axon into a narrow nodal region for excitation and an extended, insulated internodal region for efficient spread of passive current. This anatomical demarcation produces a dramatic heterogeneity in ionic fluxes during excitation, a classical example being the restriction of Na influx at the node. Recent studies have revealed that action potentials also induce calcium influx into myelinated axons of mammalian optic nerves. Does calcium influx in myelinated axons show spatial heterogeneity during nerve excitation? To address this, we analyzed spatial profiles of axonal calcium transients during action potentials by selectively staining axons with calcium indicators and subjected the data to theoretical analysis with parameters for axial calcium diffusion empirically determined using photolysis of caged compounds. The results show surprisingly that during action potentials, calcium influx occurs uniformly along an axon of a fully myelinated mouse optic nerve. PMID:16835363

  18. Gauge invariant actions for string models

    SciTech Connect

    Banks, T.

    1986-06-01

    String models of unified interactions are elegant sets of Feynman rules for the scattering of gravitons, gauge bosons, and a host of massive excitations. The purpose of these lectures is to describe the progress towards a nonperturbative formulation of the theory. Such a formulation should make the geometrical meaning of string theory manifest and explain the many ''miracles'' exhibited by the string Feynman rules. There are some new results on gauge invariant observables, on the cosmological constant, and on the symmetries of interacting string field theory. 49 refs.

  19. Action potential energy efficiency varies among neuron types in vertebrates and invertebrates.

    PubMed

    Sengupta, Biswa; Stemmler, Martin; Laughlin, Simon B; Niven, Jeremy E

    2010-01-01

    The initiation and propagation of action potentials (APs) places high demands on the energetic resources of neural tissue. Each AP forces ATP-driven ion pumps to work harder to restore the ionic concentration gradients, thus consuming more energy. Here, we ask whether the ionic currents underlying the AP can be predicted theoretically from the principle of minimum energy consumption. A long-held supposition that APs are energetically wasteful, based on theoretical analysis of the squid giant axon AP, has recently been overturned by studies that measured the currents contributing to the AP in several mammalian neurons. In the single compartment models studied here, AP energy consumption varies greatly among vertebrate and invertebrate neurons, with several mammalian neuron models using close to the capacitive minimum of energy needed. Strikingly, energy consumption can increase by more than ten-fold simply by changing the overlap of the Na(+) and K(+) currents during the AP without changing the APs shape. As a consequence, the height and width of the AP are poor predictors of energy consumption. In the Hodgkin-Huxley model of the squid axon, optimizing the kinetics or number of Na(+) and K(+) channels can whittle down the number of ATP molecules needed for each AP by a factor of four. In contrast to the squid AP, the temporal profile of the currents underlying APs of some mammalian neurons are nearly perfectly matched to the optimized properties of ionic conductances so as to minimize the ATP cost. PMID:20617202

  20. Postnatal maturation of rat hypothalamoneurohypophysial neurons: evidence for a developmental decrease in calcium entry during action potentials.

    PubMed

    Widmer, H; Amerdeil, H; Fontanaud, P; Desarménien, M G

    1997-01-01

    Action potentials and voltage-gated currents were studied in acutely dissociated neurosecretory cells from the rat supraoptic nucleus during the first three postnatal weeks (PW1-PW3), a period corresponding to the final establishment of neuroendocrine relationships. Action potential duration (at half maximum) decreased from 2.7 to 1.8 ms; this was attributable to a decrease in decay time. Application of cadmium (250 microM) reduced the decay time by 43% at PW1 and 21% at PW3, indicating that the contribution of calcium currents to action potentials decreased during postnatal development. The density of high-voltage-activated calcium currents increased from 4.4 to 10.1 pA/pF at postnatal days 1-5 and 11-14, respectively. The conductance density of sustained potassium current, measured at +20 mV, increased from 0.35 (PW1) to 0.53 (PW3) nS/pF. The time to half-maximal amplitude did not change. Conductance density and time- and voltage-dependent inactivation of the transient potassium current were stable from birth. At PW1, the density and time constant of decay (measured at 0 mV) were 0.29 nS/pF (n = 12) and 17.9 ms (n = 10), respectively. Voltage-dependent properties and density (1.1 nS/pF) of the sodium current did not change postnatally. During PW1, fitting the mean activation data with a Boltzmann function gave a half-activation potential of -25 mV. A double Boltzman equation was necessary to adequately fit the inactivation data, suggesting the presence of two populations of sodium channels. One population accounted for approximately 14% of the channels, with a half-inactivation potential of -86 mV; the remaining population showed a half-inactivation potential of -51 mV. A mathematical model, based on Hodgkin-Huxley equations, was used to assess the respective contributions of individual currents to the action potential. When the densities of calcium and sustained potassium currents were changed from immature to mature values, the decay time of the action

  1. "Ordinary men" or "evil monsters"? An action systems model of genocidal actions and characteristics of perpetrators.

    PubMed

    Hollows, Kerrilee; Fritzon, Katarina

    2012-10-01

    This study aimed to address the limitations of the existing genocide literature with the development of an empirically based classification system. Using Shye's (1985) action systems model, it was hypothesized that four types of perpetrators would exist and would be distinguishable by differences in the sources and target of individual criminal actions. Court transcripts from 80 perpetrators sentenced by the international courts were subject to content analysis and revealed 39 offense action variables, 17 perpetrator characteristic variables, and 6 perpetrator motive variables. A smallest space analysis using the Jaccard coefficient of association was conducted on the offense variables. The results supported the proposed framework, producing four distinct types of genocidal perpetrators. Correlational analyses were then conducted to examine the relationships between each of the perpetrator types and the remaining variables. The results of those correlations provided further support for the proposed framework. The implications of these findings are discussed. PMID:22353044

  2. A Fast Na+/Ca2+-Based Action Potential in a Marine Diatom

    PubMed Central

    Taylor, Alison R.

    2009-01-01

    Background Electrical impulses in animals play essential roles in co-ordinating an array of physiological functions including movement, secretion, environmental sensing and development. Underpinning many of these electrical signals is a fast Na+-based action potential that has been fully characterised only in cells associated with the neuromuscular systems of multicellular animals. Such rapid action potentials are thought to have evolved with the first metazoans, with cnidarians being the earliest representatives. The present study demonstrates that a unicellular protist, the marine diatom Odontella sinensis, can also generate a fast Na+/Ca2+ based action potential that has remarkably similar biophysical and pharmacological properties to invertebrates and vertebrate cardiac and skeletal muscle cells. Methodology/Principal Findings The kinetic, ionic and pharmacological properties of the rapid diatom action potential were examined using single electrode current and voltage clamp techniques. Overall, the characteristics of the fast diatom currents most closely resemble those of vertebrate and invertebrate muscle Na+/Ca2+ currents. Conclusions/Significance This is the first demonstration of voltage-activated Na+ channels and the capacity to generate fast Na+-based action potentials in a unicellular photosynthetic organism. The biophysical and pharmacological characteristics together with the presence of a voltage activated Na+/Ca2+ channel homologue in the recently sequenced genome of the diatom Thalassiosira pseudonana, provides direct evidence supporting the hypothesis that this rapid signalling mechanism arose in ancestral unicellular eukaryotes and has been retained in at least two phylogenetically distant lineages of eukaryotes; opisthokonts and the stramenopiles. The functional role of the fast animal-like action potential in diatoms remains to be elucidated but is likely involved in rapid environmental sensing of these widespread and successful marine protists

  3. Taking Research into Schools: The West Lothian Action Enquiry Model

    ERIC Educational Resources Information Center

    Binnie, Lynne M.; Allen, Kristen; Beck, Elaine

    2008-01-01

    This paper outlines the efforts of an Educational Psychology Service (EPS) to develop its practice in the area of research. It will argue that the Action Enquiry model of service delivery can empower teaching staff and may allow an effective means of change and improvement to take place in schools. This model steers research towards providing…

  4. Inter-Subject Variability in Human Atrial Action Potential in Sinus Rhythm versus Chronic Atrial Fibrillation

    PubMed Central

    Sánchez, Carlos; Bueno-Orovio, Alfonso; Wettwer, Erich; Loose, Simone; Simon, Jana; Ravens, Ursula; Pueyo, Esther; Rodriguez, Blanca

    2014-01-01

    Aims Human atrial electrophysiology exhibits high inter-subject variability in both sinus rhythm (SR) and chronic atrial fibrillation (cAF) patients. Variability is however rarely investigated in experimental and theoretical electrophysiological studies, thus hampering the understanding of its underlying causes but also its implications in explaining differences in the response to disease and treatment. In our study, we aim at investigating the ability of populations of human atrial cell models to capture the inter-subject variability in action potential (AP) recorded in 363 patients both under SR and cAF conditions. Methods and Results Human AP recordings in atrial trabeculae (n = 469) from SR and cAF patients were used to calibrate populations of computational SR and cAF atrial AP models. Three populations of over 2000 sampled models were generated, based on three different human atrial AP models. Experimental calibration selected populations of AP models yielding AP with morphology and duration in range with experimental recordings. Populations using the three original models can mimic variability in experimental AP in both SR and cAF, with median conductance values in SR for most ionic currents deviating less than 30% from their original peak values. All cAF populations show similar variations in GK1, GKur and Gto, consistent with AF-related remodeling as reported in experiments. In all SR and cAF model populations, inter-subject variability in IK1 and INaK underlies variability in APD90, variability in IKur, ICaL and INaK modulates variability in APD50 and combined variability in Ito and IKur determines variability in APD20. The large variability in human atrial AP triangulation is mostly determined by IK1 and either INaK or INaCa depending on the model. Conclusion Experimentally-calibrated human atrial AP models populations mimic AP variability in SR and cAF patient recordings, and identify potential ionic determinants of inter-subject variability in

  5. The neuroendocrine action potential. Winner of the 2008 Frank Beach Award in Behavioral Neuroendocrinology.

    PubMed

    Hofmann, Hans A

    2010-09-01

    Animals are remarkably well equipped to respond to changes in their environment across different time scales and levels of biological organization. Here, I introduce a novel perspective that incorporates the three main processes the nervous system uses to integrate and process information: electrophysiological, genomic, and neuroendocrine action potentials. After discussing several examples of neuroendocrine action potentials, I lay out the commonalities of these temporally organized responses and how they might be interrelated with electrophysiological activity and genomic responses. This framework provides a novel outlook on longstanding questions in behavioral neuroendocrinology and suggests exciting new avenues for further research that will integrate across disciplines and levels of biological organization. PMID:20600047

  6. Effects of some heavy metals on the action potentials of an identified Helix pomatia photosensitive neuron.

    PubMed

    Kartelija, Gordana; Radenović, Lidija; Todorović, Natasa; Nedeljković, Miodrag

    2005-06-01

    In the photosensitive MB neuron in the left parietal ganglion of Helix pomatia, the onset of light prolongs significantly (by about 40%) the duration of the action potential. The broadening of the action potential after the onset of light was found to be due to its calcium component and could not be induced after blocking Ca(2+) channels by Cd(2+) and Pb(2+) and in absence of Ca(2+) in medium. The blocking effect of both compounds was reversible. It was found that CdCl(2) exhibited a more intense blocking effect than PbCl(2). PMID:16154952

  7. Spatiotemporal pattern of action potential firing in developing inner hair cells of the mouse cochlea.

    PubMed

    Sendin, Gaston; Bourien, Jérôme; Rassendren, François; Puel, Jean-Luc; Nouvian, Régis

    2014-02-01

    Inner hair cells (IHCs) are the primary transducer for sound encoding in the cochlea. In contrast to the graded receptor potential of adult IHCs, immature hair cells fire spontaneous calcium action potentials during the first postnatal week. This spiking activity has been proposed to shape the tonotopic map along the ascending auditory pathway. Using perforated patch-clamp recordings, we show that developing IHCs fire spontaneous bursts of action potentials and that this pattern is indistinguishable along the basoapical gradient of the developing cochlea. In both apical and basal IHCs, the spiking behavior undergoes developmental changes, where the bursts of action potential tend to occur at a regular time interval and have a similar length toward the end of the first postnatal week. Although disruption of purinergic signaling does not interfere with the action potential firing pattern, pharmacological ablation of the α9α10 nicotinic receptor elicits an increase in the discharge rate. We therefore suggest that in addition to carrying place information to the ascending auditory nuclei, the IHCs firing pattern controlled by the α9α10 receptor conveys a temporal signature of the cochlear development. PMID:24429348

  8. CCA-1, EGL-19 and EXP-2 currents shape action potentials in the Caenorhabditis elegans pharynx

    PubMed Central

    Shtonda, Boris; Avery, Leon

    2005-01-01

    The pharynx of Caenorhabditis elegans is a tubular muscle controlled by its own set of neurons. We developed a technique to voltage clamp the pharyngeal muscle and demonstrate by analyzing mutants that the pharyngeal action potential is regulated by three major voltage-gated currents, conducted by a T-type calcium channel CCA-1, an L-type calcium channel EGL-19 and a potassium channel EXP-2. We show that CCA-1 exhibits T-type calcium channel properties: activation at −40 mV and rapid inactivation. Our results suggest that CCA-1’s role is to accelerate the action potential upstroke in the pharyngeal muscle in response to excitatory inputs. Similarly to other L-type channels, EGL-19 activates at high voltages and inactivates slowly; thus it may maintain the plateau phase of the action potential. EXP-2 is a potassium channel of the kV family that shows inward rectifier properties when expressed in Xenopus laevis oocytes. We show that endogenous EXP-2 is not a true inward rectifier – it conducts large outward currents at potentials up to +20 mV and is therefore well suited to trigger rapid repolarization at the end of the action potential plateau phase. Our results suggest that EXP-2 is a potassium channel with unusual properties that uses a hyperpolarization threshold to activate a regenerative hyperpolarizing current. PMID:15914661

  9. Wogonin potentiates the antitumor action of etoposide and ameliorates its adverse effects.

    PubMed

    Enomoto, Riyo; Koshiba, Chika; Suzuki, Chie; Lee, Eibai

    2011-05-01

    Wogonin, a flavone in the roots of Scutellaria baicalensis, reduced etoposide-induced apoptotic cell death in normal cells, such as bone marrow cells and thymocytes. On the other hand, wogonin potentiated the proapoptotic or cytotoxic action of etoposide in tumor cells, such as Jurkat, HL-60, A549, and NCI-H226. These contradictory actions of wogonin on apoptosis are distinguished by normal or cancer cell types. Wogonin had no effect on apoptosis induced by other anticancer agents in the tumor cells. Thus, the potentiation effect of wogonin was observed only in etoposide-induced apoptosis in tumor cells. In a functional assay for P-glycoprotein (P-gp), wogonin suppressed excretion of calcein, a substrate for P-gp, in these tumor cells. Moreover, wogonin decreased the excretion of radiolabeled etoposide and accordingly increased intracellular content of this agent in the cells. P-gp inhibitors showed a similar potentiation effect on etoposide-induced apoptosis in these tumor cells. Thus, wogonin is likely to potentiate the anticancer action of etoposide due to P-gp inhibition and accumulation of this agent. These findings suggest that wogonin may be a useful chemotherapeutic adjuvant to potentiate the pharmacological action of etoposide and ameliorate its adverse effects. PMID:20658136

  10. 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

  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. PMID:26686984

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

    SciTech Connect

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

    2013-04-26

    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 compound 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.

  13. 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

    2014-03-01

    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 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. PMID:24599470

  14. 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

  15. Animated pose templates for modeling and detecting human actions.

    PubMed

    Yao, Benjamin Z; Nie, Bruce X; Liu, Zicheng; Zhu, Song-Chun

    2014-03-01

    This paper presents animated pose templates (APTs) for detecting short-term, long-term, and contextual actions from cluttered scenes in videos. Each pose template consists of two components: 1) a shape template with deformable parts represented in an And-node whose appearances are represented by the Histogram of Oriented Gradient (HOG) features, and 2) a motion template specifying the motion of the parts by the Histogram of Optical-Flows (HOF) features. A shape template may have more than one motion template represented by an Or-node. Therefore, each action is defined as a mixture (Or-node) of pose templates in an And-Or tree structure. While this pose template is suitable for detecting short-term action snippets in two to five frames, we extend it in two ways: 1) For long-term actions, we animate the pose templates by adding temporal constraints in a Hidden Markov Model (HMM), and 2) for contextual actions, we treat contextual objects as additional parts of the pose templates and add constraints that encode spatial correlations between parts. To train the model, we manually annotate part locations on several keyframes of each video and cluster them into pose templates using EM. This leaves the unknown parameters for our learning algorithm in two groups: 1) latent variables for the unannotated frames including pose-IDs and part locations, 2) model parameters shared by all training samples such as weights for HOG and HOF features, canonical part locations of each pose, coefficients penalizing pose-transition and part-deformation. To learn these parameters, we introduce a semi-supervised structural SVM algorithm that iterates between two steps: 1) learning (updating) model parameters using labeled data by solving a structural SVM optimization, and 2) imputing missing variables (i.e., detecting actions on unlabeled frames) with parameters learned from the previous step and progressively accepting high-score frames as newly labeled examples. This algorithm belongs to a

  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 actions. 1945.19 Section 1945.19 Agriculture Regulations of the Department of Agriculture (Continued... AGENCY, DEPARTMENT OF AGRICULTURE (CONTINUED) PROGRAM REGULATIONS (CONTINUED) EMERGENCY...

  17. 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…

  18. Primary cortical representation of sounds by the coordination of action-potential timing

    NASA Astrophysics Data System (ADS)

    Decharms, R. Christopher; Merzenich, Michael M.

    1996-06-01

    CORTICAL population coding could in principle rely on either the mean rate of neuronal action potentials, or the relative timing of action potentials, or both. When a single sensory stimulus drives many neurons to fire at elevated rates, the spikes of these neurons become tightly synchronized1,2, which could be involved in 'binding' together individual firing-rate feature representations into a unified object percept3. Here we demonstrate that the relative timing of cortical action potentials can signal stimulus features themselves, a function even more basic than feature grouping. Populations of neurons in the primary auditory cortex can coordinate the relative timing of their action potentials such that spikes occur closer together in time during continuous stimuli. In this way cortical neurons can signal stimuli even when their firing rates do not change. Population coding based on relative spike timing can systematically signal stimulus features, it is topographically mapped, and it follows the stimulus time course even where mean firing rate does not.

  19. 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…

  20. Transpolar potential saturation models compared

    NASA Astrophysics Data System (ADS)

    Siscoe, G.; Raeder, J.; Ridley, A. J.

    2004-09-01

    We compare four explanations of transpolar potential saturation: (1) the magnetic field at the stagnation point weakens, thereby limiting magnetic reconnection; (2) a dimple develops at the stagnation point, which limits the inflow rate to the reconnection line; (3) the magnetopause becomes blunt and the bow shock recedes, thus giving more room for the solar wind to flow around the magnetosphere, thereby reducing the need for magnetic reconnection; (4) the region 1 current system usurps the Chapman-Ferraro current system and saturates when the J × B force it generates balances solar wind ram pressure. The paper's point is that all four mechanisms involve a limit on the strength of the region 1 current system and that the criterion for the onset of transpolar potential saturation in each mechanism is that the region 1 current system generates a magnetic field that is about as strong as the dipole field at the dayside magnetopause. This circumstance prevents tests to discriminate between the four mechanisms based on predictions that relate to their dependencies on the region 1 current system. The group as a whole, however, can be tested to see whether their common criterion that relates the onset of transpolar potential saturation to the total current flowing in the region 1 system holds. The criterion can be formulated in terms of predictions that relate transpolar potential saturation to the strength of the interplanetary electric field, solar wind ram pressure, and ionospheric conductance. Published data analyses and MHD simulations reasonably confirm these predictions.

  1. Optical recording of action potentials with second-harmonic generation microscopy.

    PubMed

    Dombeck, Daniel A; Blanchard-Desce, Mireille; Webb, Watt W

    2004-01-28

    Nonlinear microscopy has proven to be essential for neuroscience investigations of thick tissue preparations. However, the optical recording of fast (approximately 1 msec) cellular electrical activity has never until now been successfully combined with this imaging modality. Through the use of second-harmonic generation microscopy of primary Aplysia neurons in culture labeled with 4-[4-(dihexylamino)phenyl][ethynyl]-1-(4-sulfobutyl)pyridinium (inner salt), we optically recorded action potentials with 0.833 msec temporal and 0.6 microm spatial resolution on soma and neurite membranes. Second-harmonic generation response as a function of change in membrane potential was found to be linear with a signal change of approximately 6%/100 mV. The signal-to-noise ratio was approximately 1 for single-trace action potential recordings but was readily increased to approximately 6-7 with temporal averaging of approximately 50 scans. Photodamage was determined to be negligible by observing action potential characteristics, cellular resting potential, and gross cellular morphology during and after laser illumination. High-resolution (micrometer scale) optical recording of membrane potential activity by previous techniques has been limited to imaging depths an order of magnitude less than nonlinear methods. Because second-harmonic generation is capable of imaging up to approximately 400 microm deep into intact tissue with submicron resolution and little out-of-focus photodamage or bleaching, its ability to record fast electrical activity should prove valuable to future electrophysiology studies. PMID:14749445

  2. Cellular electrophysiology of canine pulmonary vein cardiomyocytes: action potential and ionic current properties

    PubMed Central

    Ehrlich, Joachim R; Cha, Tae-Joon; Zhang, Liming; Chartier, Denis; Melnyk, Peter; Hohnloser, Stefan H; Nattel, Stanley

    2003-01-01

    Pulmonary vein (PV) cardiomyocytes play an important role in atrial fibrillation; however, little is known about their specific cellular electrophysiological properties. We applied standard microelectrode recording and whole-cell patch-clamp to evaluate action potentials and ionic currents in canine PVs and left atrium (LA) free wall. Resting membrane potential (RMP) averaged −66 ± 1 mV in PVs and −74 ± 1 mV in LA (P < 0.0001) and action potential amplitude averaged 76 ± 2 mV in PVs vs. 95 ± 2 mV in LA (P < 0.0001). PVs had smaller maximum phase 0 upstroke velocity (Vmax: 98 ± 9 vs. 259 ± 16 V s−1, P < 0.0001) and action potential duration (APD): e.g. at 2 Hz, APD to 90 % repolarization in PVs was 84 % of LA (P < 0.05). Na+ current density under voltage-clamp conditions was similar in PV and LA, suggesting that smaller Vmax in PVs was due to reduced RMP. Inward rectifier current density in the PV cardiomyocytes was ˜58 % that in the LA, potentially accounting for the less negative RMP in PVs. Slow and rapid delayed rectifier currents were greater in the PV (by ˜60 and ˜50 %, respectively), whereas transient outward K+ current and L-type Ca2+ current were significantly smaller (by ˜25 and ˜30 %, respectively). Na+-Ca2+-exchange (NCX) current and T-type Ca2+ current were not significantly different. In conclusion, PV cardiomyocytes have a discrete distribution of transmembrane ion currents associated with specific action potential properties, with potential implications for understanding PV electrical activity in cardiac arrhythmias. PMID:12847206

  3. Sodium-calcium exchange during the action potential in guinea-pig ventricular cells.

    PubMed Central

    Egan, T M; Noble, D; Noble, S J; Powell, T; Spindler, A J; Twist, V W

    1989-01-01

    1. Slow inward tail currents attributable to electrogenic sodium-calcium exchange can be recorded by imposing hyperpolarizing voltage clamp pulses during the normal action potential of isolated guinea-pig ventricular cells. The hyperpolarizations return the membrane to the resting potential (between -65 and -88 m V) allowing an inward current to be recorded. This current usually has peak amplitude when repolarization is imposed during the first 50 ms after the action potential upstroke, but becomes negligible once the final phase of repolarization is reached. The envelope of peak current tail amplitudes strongly resembles that of the intracellular calcium transient recorded in other studies. 2. Repetitive stimulation producing normal action potentials at a frequency of 2 Hz progressively augments the tail current recorded immediately after the stimulus train. Conversely, if each action potential is prematurely terminated at 0.1 Hz, repetitive stimulation produces a tail current much smaller than the control value. The control amplitude of inward current is only maintained if interrupted action potentials are separated by at least one full 'repriming' action potential. These effects mimic those on cell contraction (Arlock & Wohlfart, 1986) and suggest that progressive changes in tail current are controlled by variations in the amplitude and time course of the intracellular calcium transient. 3. When intracellular calcium is buffered sufficiently to abolish contraction, the tail current is abolished. Substitution of calcium with strontium greatly reduces the tail current. 4. The inward tail current can also be recorded at more positive membrane potentials using standard voltage clamp pulse protocols. In this way it was found that temperature has a large effect on the tail current, which can change from net inward at 22 degrees C to net outward at 37 degrees C. The largest inward currents are usually recorded at about 30 degrees C. It is shown that this effect is

  4. Developing a Model for Continuous Professional Development by Action Research

    ERIC Educational Resources Information Center

    Herbert, Susan; Rainford, Marcia

    2014-01-01

    This paper presents a case study of the work of two teacher educators with an in-service science teacher. This case study forms one cycle of a larger action research study that will eventually lead to a model of how the third-space concept for teacher professional development can be realized in natural school settings. The case study took place in…

  5. Action Research: A Developmental Model of Professional Socialization

    ERIC Educational Resources Information Center

    Schoen, Sharon

    2007-01-01

    This article proposes a developmental model to socialize teachers at all levels (preservice, novice, and experienced) and in all positions (general education, special education, elementary school, middle school, and high school) in the methodology of action research. A process for advancing professional understanding is theorized to include the…

  6. Developmental Model of Democratic Values and Attitudes toward Social Actions

    ERIC Educational Resources Information Center

    Papanastasiou, Constantinos; Koutselini, Mary

    2003-01-01

    This article presents the Cyprus results, and proposes a model of home environment and school climate on the social participation of ninth graders based on the IEA 1999 CIVIC education study data. This study examined ninth graders' participation in social actions by means of a questionnaire; the data were analyzed using structural equation…

  7. Participatory Action Research as a Model for Conducting Family Research.

    ERIC Educational Resources Information Center

    Turnbull, Ann P.; Friesen, Barbara J.; Ramirez, Carmen

    1998-01-01

    This article discusses a participatory action research (PAR) approach to conducting family research. It proposes a model of PAR implementation level including the options of family members as research leaders and researchers as ongoing advisors, researchers and family members as coresearchers, and researches as leaders, and family members as…

  8. The DBI action, higher-derivative supergravity, and flattening inflaton potentials

    NASA Astrophysics Data System (ADS)

    Bielleman, Sjoerd; Ibáñez, Luis E.; Pedro, Francisco G.; Valenzuela, Irene; Wieck, Clemens

    2016-05-01

    In string theory compactifications it is common to find an effective Lagrangian for the scalar fields with a non-canonical kinetic term. We study the effective action of the scalar position moduli of Type II D p-branes. In many instances the kinetic terms are in fact modified by a term proportional to the scalar potential itself. This can be linked to the appearance of higher-dimensional supersymmetric operators correcting the Kähler potential. We identify the supersymmetric dimension-eight operators describing the α' corrections captured by the D-brane Dirac-Born-Infeld action. Our analysis then allows an embedding of the D-brane moduli effective action into an {N}=1 supergravity formulation. The effects of the potential-dependent kinetic terms may be very important if one of the scalars is the inflaton, since they lead to a flattening of the scalar potential. We analyze this flattening effect in detail and compute its impact on the CMB observables for single-field inflation with monomial potentials.

  9. Toward a system to measure action potential on mice brain slices with local magnetoresistive probes

    SciTech Connect

    Amaral, J.; Cardoso, S.; Freitas, P. P.; Sebastiao, A. M.

    2011-04-01

    This work combines an electrophysiological system with a magnetoresistive chip to measure the magnetic field created by the synaptic/action potential currents. The chip, with 15 spin valve sensors, was designed to be integrated in a recording chamber for submerged mice brain slices used for synaptic potential measurements. Under stimulation (rectangular pulses of 0.1 ms every 10 s) through a concentric electrode placed near the CA3/CA1 border of the hippocampus, the spin valve sensor readout signals with 20 {mu}V amplitude and a pulse length of 20 to 30 ms were recorded only in the pyramidal cell bodies region and can be interpreted as being derived from action potentials/currents.

  10. MODEL HARMONIZATION POTENTIAL AND BENEFITS

    EPA Science Inventory

    The IPCS Harmonization Project, which is currently ongoing under the auspices of the WHO, in the context of chemical risk assessment or exposure modeling, does not imply global standardization. Instead, harmonization is thought of as an effort to strive for consistency among appr...

  11. Novel Transabdominal Motor Action Potential (TaMAP) Neuromonitoring System for Spinal Surgery

    PubMed Central

    Feldman, Erica; Gabel, Brandon C; Taylor, Natalie; Gharib, James; Lee, Yu-Po; Taylor, William

    2016-01-01

    Introduction Minimally invasive lateral lumbar interbody fusion (LLIF) approaches to the lumbar spine reduce patient morbidity compared to anterior or posterior alternatives. This approach, however, decreases direct anatomical visualization, creating the need for highly sensitive and specific neurophysiological monitoring. We seek to determine feasibility in 'transabdominal motor action potential (TaMAP)' monitoring as an assessment for the integrity of the neural elements during lateral-approach surgeries to the lumbar spine.  Methods Cathode and anode leads were placed on the posterior and anterior surfaces of two porcine subjects. Currents of varying degrees were transmitted across, from front to back. Motor responses were monitored and recorded by needle electrodes in specific distal muscle groups of the lower extremity. Lastly, the cathode and anode were placed anterior and posterior to the chest wall and stimulated to the maximum of 1500 mA to determine any effect on cardiac rhythm. Results Responses were seen by measuring vertical height differences between peaks of corresponding evoked potentials. Recruitment began at 200 mA in the lower extremities. Stimulation at 450 mA recruited a reliable and distinguishable electrographic response from most muscle groups. Responses were recorded and reliably measured and increased in proportion to the graduation of transabdominal stimulation current; no responses were seen in the arms or face. 1500 mA across the chest wall failed to stimulate or induce cardiac arrhythmia on repeated stimulation, indicating safety of stimulation. Conclusion TaMAPs seen in the animal model provide a potential alternative to standard transcranial motor evoked potentials done in the lateral approach of LLIFs. TaMAP recordings in most muscle groups were recordable and reliable, though some muscle groups failed to stimulate. Safety of transabdominal motor evoked potentials was confirmed in this porcine study. Future studies

  12. Effective action for the Abelian Higgs model in FLRW

    SciTech Connect

    George, Damien P.; Mooij, Sander; Postma, Marieke E-mail: smooij@nikhef.nl

    2012-11-01

    We compute the divergent contributions to the one-loop action of the U(1) Abelian Higgs model. The calculation allows for a Friedmann-Lemaitre-Robertson-Walker space-time and a time-dependent expectation value for the scalar field. Treating the time-dependent masses as two-point interactions, we use the in-in formalism to compute the first, second and third order graphs that contribute quadratic and logarithmic divergences to the effective scalar action. Working in R{sub ξ} gauge we show that the result is gauge invariant upon using the equations of motion.

  13. Mechanism of Action of IL-7 and Its Potential Applications and Limitations in Cancer Immunotherapy

    PubMed Central

    Gao, Jianbao; Zhao, Lintao; Wan, Yisong Y.; Zhu, Bo

    2015-01-01

    Interleukin-7 (IL-7) is a non-hematopoietic cell-derived cytokine with a central role in the adaptive immune system. It promotes lymphocyte development in the thymus and maintains survival of naive and memory T cell homeostasis in the periphery. Moreover, it is important for the organogenesis of lymph nodes (LN) and for the maintenance of activated T cells recruited into the secondary lymphoid organs (SLOs). The immune capacity of cancer patients is suppressed that is characterized by lower T cell counts, less effector immune cells infiltration, higher levels of exhausted effector cells and higher levels of immunosuppressive cytokines, such as transforming growth factor β (TGF-β). Recombinant human IL-7 (rhIL-7) is an ideal solution for the immune reconstitution of lymphopenia patients by promoting peripheral T cell expansion. Furthermore, it can antagonize the immunosuppressive network. In animal models, IL-7 has been proven to prolong the survival of tumor-bearing hosts. In this review, we will focus on the mechanism of action and applications of IL-7 in cancer immunotherapy and the potential restrictions for its usage. PMID:25955647

  14. Groundwater modeling in RCRA assessment, corrective action design and evaluation

    SciTech Connect

    Rybak, I.; Henley, W.

    1995-12-31

    Groundwater modeling was conducted to design, implement, modify, and terminate corrective action at several RCRA sites in EPA Region 4. Groundwater flow, contaminant transport and unsaturated zone air flow models were used depending on the complexity of the site and the corrective action objectives. Software used included Modflow, Modpath, Quickflow, Bioplume 2, and AIR3D. Site assessment data, such as aquifer properties, site description, and surface water characteristics for each facility were used in constructing the models and designing the remedial systems. Modeling, in turn, specified additional site assessment data requirements for the remedial system design. The specific purpose of computer modeling is discussed with several case studies. These consist, among others, of the following: evaluation of the mechanism of the aquifer system and selection of a cost effective remedial option, evaluation of the capture zone of a pumping system, prediction of the system performance for different and difficult hydrogeologic settings, evaluation of the system performance, and trouble-shooting for the remedial system operation. Modeling is presented as a useful tool for corrective action system design, performance, evaluation, and trouble-shooting. The case studies exemplified the integration of diverse data sources, understanding the mechanism of the aquifer system, and evaluation of the performance of alternative remediation systems in a cost-effective manner. Pollutants of concern include metals and PAHs.

  15. Agent-based model of macrophage action on endocrine pancreas.

    PubMed

    Martínez, Ignacio V; Gómez, Enrique J; Hernando, M Elena; Villares, Ricardo; Mellado, Mario

    2012-01-01

    This paper proposes an agent-based model of the action of macrophages on the beta cells of the endocrine pancreas. The aim of this model is to simulate the processes of beta cell proliferation and apoptosis and also the process of phagocytosis of cell debris by macrophages, all of which are related to the onset of the autoimmune response in type 1 diabetes. We have used data from the scientific literature to design the model. The results show that the model obtains good approximations to real processes and could be used to shed light on some open questions concerning such processes. PMID:23155767

  16. Understanding the cardiovascular actions of soy isoflavones: potential novel targets for antihypertensive drug development.

    PubMed

    Martin, Doug; Song, Jin; Mark, Connie; Eyster, Kathleen

    2008-12-01

    Interest in and use of "natural" remedies has grown exponentially in recent years. Compounds that have attracted considerable attention are the isoflavones, particular those found in soy. This review will provide a critical evaluation of our current understanding of the effects, mechanisms of action, and potential clinical applications of soy isoflavones in hypertension. Current data indicate that soy isoflavones, such as genistein and daidzein and equol, relax vascular smooth muscle both in vitro and in vivo via a combination of mechanisms including potentiation of endothelial-dependent and endothelial-independent vasodilator systems and inhibition of constrictor mechanisms. These effects involve both classical genomic as well non genomic actions. Isoflavone actions are mediated in part via interactions with estrogen receptors where soy isoflavones induce unique receptor conformations and exert tissue dependent effects similar to the selective estrogen receptor modulators. Signaling pathways such as ERK1/2, PI3-Kinase/Akt and cAMP contribute to isoflavone isoflavone activation of eNOS in the vasculature as well. Isoflavones also target the kidney to increase renal blood flow and sodium excretion. Finally, soy isoflavones interact with humoral systems such as the renin angiotensin. Data from animal studies show consistently that the aggregate effect of these actions is attenuation of hypertension. In contrast, studies in humans remain controversial. Recent data also suggest that analogues of isoflavones may possess unique vascular actions. Thus significant opportunity remains for study of the effects and mechanisms of action of soy isoflavones on hypertension in both animals and humans. PMID:19202595

  17. Spontaneous muscle action potentials fail to develop without fetal-type acetylcholine receptors

    PubMed Central

    Takahashi, Masazumi; Kubo, Tai; Mizoguchi, Akira; Carlson, C. George; Endo, Katsuaki; Ohnishi, Katsunori

    2002-01-01

    In mammals, two combinations of muscle nicotinic acetylcholine receptors (AChRs) are used: α2βγδ (γ-AChR) or α2βɛδ (ɛ-AChR). After birth, γ-AChRs are replaced by ɛ-AChRs (γ/ɛ-switch). The two receptors have different conductances and open times. During perinatal period, the long open time γ-AChRs generate random myofiber action potentials from uniquantal miniature end-plate potentials (mEPPs). ɛ-AChRs are suitable for strong adult muscle activities. Since the effect of the γ/ɛ-switch on neuromuscular development was unclear, despite the many differences in channel characteristics, we carried out this study to generate γ-subunit-deficient mice. Homozygotes born alive survived for 2 days in a stable condition, and were able to move their forelimbs. Endplate AChRs included ɛ-subunits, and muscle fibers had multiple neuromuscular junctions. Both pre- and postsynapses were abnormal and spontaneous action potentials generated from mEPPs were totally absent. Results suggest a requirement for γ-AChRs in mediating synaptically-induced action potential activity critical for neuromuscular development. PMID:12101101

  18. Event-related potentials reveal early activation of body part representations in action concept comprehension.

    PubMed

    Lu, Aitao; Liu, Jing; Zhang, John X

    2012-03-01

    With tasks involving action concept comprehension, many fMRI studies have reported brain activations in sensori-motor regions specific to effectors of the referent action. There is relatively less evidence whether such activations reflect early semantic access or late conceptual re-processing. Here we recorded event-related potentials when participants recognized noun-verb pairs. For Congruent pairs, the verb was the one most commonly associated with the noun (e.g., football-kick). Compared with a control condition, verbs in Congruent pairs showed priming effects in the time windows of 100-150 ms and 210-260 ms. Such activation seems to be specific to body part but not other aspects of the action as similar priming effect was also found when the noun and verb involved different actions though sharing the same body part (e.g., football-jump), documenting for the first time the early activation of body part representations in action concept comprehension. PMID:22306088

  19. Influences of the Unified Service Action Model on the HL7 Reference Information Model.

    PubMed

    Russler, D C; Schadow, G; Mead, C; Snyder, T; Quade, L M; McDonald, C J

    1999-01-01

    Modeling information for the electronic medical record (EMR) builds on a century of study on information and its relationship to cost and quality improvement. An initiative to examine the focus of cost and quality improvement and its relationship to information modeling resulted in the development of the Unified Service Action Model of healthcare processes, which focuses on the action as the center of cost accounting, quality accounting and privacy management. The application of this model to the HL7 Reference Information Model produced a simplification of the HL7 model at the cost of increased reliance on vocabulary terms for actions. PMID:10566497

  20. Potentiators of Defective ΔF508-CFTR Gating that Do Not Interfere with Corrector Action.

    PubMed

    Phuan, Puay-Wah; Veit, Guido; Tan, Joseph A; Finkbeiner, Walter E; Lukacs, Gergely L; Verkman, A S

    2015-10-01

    Combination drug therapies under development for cystic fibrosis caused by the ∆F508 mutation in cystic fibrosis transmembrane conductance regulator (CFTR) include a "corrector" to improve its cellular processing and a "potentiator" to improve its chloride channel function. Recently, it was reported that the approved potentiator N-(2,4-di-tert-butyl-5-hydroxyphenyl)-4-oxo-1,4-dihydroquinoline-3-carboxamide (Ivacaftor) reduces ∆F508-CFTR cellular stability and the efficacy of investigational correctors, including 3-(6-[([1-(2,2-difluoro-1,3-benzodioxol-5-yl)cyclopropyl]carbonyl) amino]-3-methyl-2-pyridinyl)-benzoic acid and 1-(2,2-difluoro-1,3-benzodioxol-5-yl)-N-(1-[(2R)-2,3-dihydroxypropyl]-6-fluoro-2-(2-hydroxy-1,1-dimethylethyl)-1H-indol-5-yl), which might contribute to the modest reported efficacy of combination therapy in clinical trials. Here, we report the identification and characterization of potentiators that do not interfere with ∆F508-CFTR stability or corrector action. High-throughput screening and structure-activity analysis identified several classes of potentiators that do not impair corrector action, including tetrahydrobenzothiophenes, thiooxoaminothiazoles, and pyrazole-pyrrole-isoxazoles. The most potent compounds have an EC(50) for ∆F508-CFTR potentiation down to 18 nM and do not reduce corrector efficacy in heterologous ∆F508-CFTR-expressing cells or primary cultures of ∆F508/∆F508 human bronchial epithelia. The ΔF508-CFTR potentiators also activated wild-type and G551D CFTR, albeit weakly. The efficacy of combination therapy for cystic fibrosis caused by the ∆F508 mutation may be improved by replacement of Ivacaftor with a potentiator that does not interfere with corrector action. PMID:26245207

  1. Tuning of Ranvier node and internode properties in myelinated axons to adjust action potential timing

    PubMed Central

    Ford, Marc C.; Alexandrova, Olga; Cossell, Lee; Stange-Marten, Annette; Sinclair, James; Kopp-Scheinpflug, Conny; Pecka, Michael; Attwell, David; Grothe, Benedikt

    2015-01-01

    Action potential timing is fundamental to information processing; however, its determinants are not fully understood. Here we report unexpected structural specializations in the Ranvier nodes and internodes of auditory brainstem axons involved in sound localization. Myelination properties deviated significantly from the traditionally assumed structure. Axons responding best to low-frequency sounds had a larger diameter than high-frequency axons but, surprisingly, shorter internodes. Simulations predicted that this geometry helps to adjust the conduction velocity and timing of action potentials within the circuit. Electrophysiological recordings in vitro and in vivo confirmed higher conduction velocities in low-frequency axons. Moreover, internode length decreased and Ranvier node diameter increased progressively along the distal axon segments, which simulations show was essential to ensure precisely timed depolarization of the giant calyx of Held presynaptic terminal. Thus, individual anatomical parameters of myelinated axons can be tuned to optimize pathways involved in temporal processing. PMID:26305015

  2. 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

  3. Real-time imaging of action potentials in nerves using changes in birefringence

    PubMed Central

    Badreddine, Ali H.; Jordan, Tomas; Bigio, Irving J.

    2016-01-01

    Polarized light can be used to measure the electrical activity associated with action potential propagation in nerves, as manifested in simultaneous dynamic changes in their intrinsic optical birefringence. These signals may serve as a tool for minimally invasive neuroimaging in various types of neuroscience research, including the study of neuronal activation patterns with high spatiotemporal resolution. A fast linear photodiode array was used to image propagating action potentials in an excised portion of the lobster walking leg nerve. We show that the crossed-polarized signal (XPS) can be reliably imaged over a ≥2 cm span in our custom nerve chamber, by averaging multiple-stimulation signals, and also in single-scan real-time “movies”. This demonstration paves the way toward utilizing changes in the optical birefringence to image more complex neuronal activity in nerve fibers and other organized neuronal tissue. PMID:27231635

  4. Real-time imaging of action potentials in nerves using changes in birefringence.

    PubMed

    Badreddine, Ali H; Jordan, Tomas; Bigio, Irving J

    2016-05-01

    Polarized light can be used to measure the electrical activity associated with action potential propagation in nerves, as manifested in simultaneous dynamic changes in their intrinsic optical birefringence. These signals may serve as a tool for minimally invasive neuroimaging in various types of neuroscience research, including the study of neuronal activation patterns with high spatiotemporal resolution. A fast linear photodiode array was used to image propagating action potentials in an excised portion of the lobster walking leg nerve. We show that the crossed-polarized signal (XPS) can be reliably imaged over a ≥2 cm span in our custom nerve chamber, by averaging multiple-stimulation signals, and also in single-scan real-time "movies". This demonstration paves the way toward utilizing changes in the optical birefringence to image more complex neuronal activity in nerve fibers and other organized neuronal tissue. PMID:27231635

  5. Tuning of Ranvier node and internode properties in myelinated axons to adjust action potential timing.

    PubMed

    Ford, Marc C; Alexandrova, Olga; Cossell, Lee; Stange-Marten, Annette; Sinclair, James; Kopp-Scheinpflug, Conny; Pecka, Michael; Attwell, David; Grothe, Benedikt

    2015-01-01

    Action potential timing is fundamental to information processing; however, its determinants are not fully understood. Here we report unexpected structural specializations in the Ranvier nodes and internodes of auditory brainstem axons involved in sound localization. Myelination properties deviated significantly from the traditionally assumed structure. Axons responding best to low-frequency sounds had a larger diameter than high-frequency axons but, surprisingly, shorter internodes. Simulations predicted that this geometry helps to adjust the conduction velocity and timing of action potentials within the circuit. Electrophysiological recordings in vitro and in vivo confirmed higher conduction velocities in low-frequency axons. Moreover, internode length decreased and Ranvier node diameter increased progressively along the distal axon segments, which simulations show was essential to ensure precisely timed depolarization of the giant calyx of Held presynaptic terminal. Thus, individual anatomical parameters of myelinated axons can be tuned to optimize pathways involved in temporal processing. PMID:26305015

  6. Experimental determination of compound action potential direction and propagation velocity from multi-electrode nerve cuffs.

    PubMed

    Rieger, R; Taylor, J; Comi, E; Donaldson, N; Russold, M; Mahony, C M O; McLaughlin, J A; McAdams, E; Demosthenous, A; Jarvis, J C

    2004-07-01

    Information extracted from whole-nerve electroneurograms, recorded using electrode cuffs, can provide signals to neuroprostheses. However, the amount of information that can be extracted from a single tripole is limited. This communication demonstrates how previously unavailable information about the direction of action potential propagation and velocity can be obtained using a multi-electrode cuff and that the arrangement acts as a velocity-selective filter. Results from in vitro experiments on frog nerves are presented. PMID:15234689

  7. 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. PMID:20966537

  8. Concept of relative variability of cardiac action potential duration and its test under various experimental conditions.

    PubMed

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

    2016-01-01

    Beat-to-beat variability of action potential duration (short-term variability, SV) is an intrinsic property of mammalian myocardium. Since the majority of agents and interventions affecting SV may modify also action potential duration (APD), we propose here the concept of relative SV (RSV), where changes in SV are normalized to changes in APD and these data are compared to the control SV-APD relationship obtained by lengthening or shortening of action potentials by inward and outward current injections. Based on this concept the influence of the several experimental conditions like stimulation frequency, temperature, pH, redox-state and osmolarity were examined on RSV in canine ventricular myocytes using sharp microelectrodes. RSV was increased by high stimulation frequency (cycle lengths <0.7 s), high temperature (above 37ºC), oxidative agents (H2O2), while it was decreased by reductive environment. RSV was not affected by changes in pH (within the range of 6.4-8.4) and osmolarity of the solution (between 250-350 mOsm). The results indicate that changes in beat-to-beat variability of APD must be evaluated exclusively in terms of RSV; furthermore, some experimental conditions, including the stimulation frequency, redox-state and temperature have to be controlled strictly when analyzing alterations in the short-term variability of APD. PMID:26492070

  9. Mechanisms of action potential propagation failure at sites of axon branching in the crayfish.

    PubMed Central

    Smith, D O

    1980-01-01

    1. The phenomena leading to action potential conduction block during repetitive stimulation of the excitor axon of the opener muscle in the crayfish walking leg were studied. 2. Action potentials, recorded extracellularly with micro-electrodes, failed to propagate past sites of axonal bifurcation following at least 3000 impulses; reduction of the rate or brief cessation of stimulation resulted in restored conduction. 3. Failure occurred initially at branch points located most peripherally and then more centrally as stimulation continued; this centripetal progression of the site of block resulted in a stepwise reduction of the number of synaptic terminals from which transmitter was released. 4. Prior to conduction failure, the conduction velocity and the sodium inward current of the action potentials decreased. 5. Local application of hyperpolarizing current or of physiological saline with low [K+] in the vicinity of a block can restore propagation; thus depolarization of the membrane most probably causes failure. 6. Soaking the preparation for as long as 2 hr in the metabolic inhibitor 2,4-dinitrophenol had no effect on the number of stimulus impulses before initial conduction block; however, the time required for recovery from the failure was prolonged. 7. The number of impulses prior to block was related directly to the temperature of the preparation; this had a Q10 calculated to be about 1 . 3. 8. It is suggested that during repetitive activity, the K+ gradient across the membrane is reduced, resulting in depolarization and eventually in conduction failure. PMID:7411430

  10. Shensong Yangxin capsules prevent ischemic arrhythmias by prolonging action potentials and alleviating Ca2+ overload.

    PubMed

    Zhao, Yixiu; Gao, Feng; Zhang, Yong; Wang, Hongtao; Zhu, Jiuxin; Chang, Liping; Du, Zhimin; Zhang, Yan

    2016-06-01

    Shensong Yangxin capsules (SSYX) are an effective traditional Chinese medicine that has been used to treat coronary heart disease clinically. The present study aimed to establish whether SSYX prevent ischemic arrhythmias in rats, and to explore the underlying mechanisms. Male rats were pretreated with distilled water, SSYX and amiodarone for one week. Acute myocardial ischemia (AMI) was performed to induce ischemic arrhythmias. The incidence and severity of ischemic arrhythmias were evaluated. The action potential, transient outward K+ current (Ito) and inward rectifier K+ current (IK1) of rat cardiomyocytes were measured using the patch‑clamp technique. The intracellular Ca2+ concentration of the cardiomyocytes was measured using a laser scanning confocal microscope. The results revealed that SSYX lowered the incidence of arrhythmia markedly during AMI. Furthermore, SSYX delayed the appearance, and reduced the severity, of ischemic arrhythmias compared with the control. In addition, SSYX markedly decreased the ratio of the myocardial infarction region to the whole heart. In an in vitro study, SSYX prolonged the action potential duration of rat cardiomyocytes, and inhibited Ito and IK1 markedly. Additionally, SSYX inhibited Ca2+ elevation induced by KCl in cardiomyocytes. These results suggested that SSYX prevents ischemic arrhythmia, and the underlying mechanism responsible for this process may include prolonging the action potential and alleviating Ca2+ overload. PMID:27122298

  11. Axon initial segment Ca2+ channels influence action potential generation and timing

    PubMed Central

    Bender, Kevin J.; Trussell, Laurence O.

    2009-01-01

    Summary Although action potentials are typically generated in the axon initial segment (AIS), the timing and pattern of action potentials is thought to depend on inward current originating in somatodendritic compartments. Using 2-photon imaging, we show that T- and R-type voltage-gated Ca2+ channels are co-localized with Na+ channels in the AIS of dorsal cochlear nucleus interneurons, and that activation of these Ca2+ channels is essential to the generation and timing of action potential bursts known as complex spikes. During complex spikes, where Na+-mediated spikelets fire atop slower depolarizing conductances, selective block of AIS Ca2+ channels delays spike timing and raises spike threshold. Furthermore, AIS Ca2+ channel block can decrease the number of spikelets within a complex spike, and even block single, simple spikes. Similar results were found in cortex and cerebellum. Thus, voltage-gated Ca2+ channels at the site of spike initiation play a key role in generating and shaping spike bursts. PMID:19186168

  12. Optical recording of action potentials in mammalian neurons using a microbial rhodopsin

    PubMed Central

    Kralj, Joel M.; Douglass, Adam D.; Hochbaum, Daniel R.; Maclaurin, Dougal; Cohen, Adam E.

    2011-01-01

    Reliable optical detection of single action potentials in mammalian neurons has been one of the longest-standing challenges in neuroscience. Here we achieve this goal by using the endogenous fluorescence of a microbial rhodopsin protein, Archaerhodopsin 3 (Arch) from Halorubrum sodomense, expressed in cultured rat hippocampal neurons. This genetically encoded voltage indicator exhibited an approximately 10-fold improvement in sensitivity and speed over existing protein-based voltage indicators, with a roughly linear two-fold increase in brightness between −150 mV and +150 mV and a sub-millisecond response time. Arch detected single electrically triggered action potentials with an optical signal-to-noise ratio > 10. The mutant Arch(D95N) lacked endogenous proton pumping and showed 50% greater sensitivity than wild-type, but had a slower response (41 ms). Nonetheless, Arch(D95N) also resolved individual action potentials. Microbial rhodopsin-based voltage indicators promise to enable optical interrogation of complex neural circuits, and electrophysiology in systems for which electrode-based techniques are challenging. PMID:22120467

  13. Action unit classification using active appearance models and conditional random fields.

    PubMed

    van der Maaten, Laurens; Hendriks, Emile

    2012-10-01

    In this paper, we investigate to what extent modern computer vision and machine learning techniques can assist social psychology research by automatically recognizing facial expressions. To this end, we develop a system that automatically recognizes the action units defined in the facial action coding system (FACS). The system uses a sophisticated deformable template, which is known as the active appearance model, to model the appearance of faces. The model is used to identify the location of facial feature points, as well as to extract features from the face that are indicative of the action unit states. The detection of the presence of action units is performed by a time series classification model, the linear-chain conditional random field. We evaluate the performance of our system in experiments on a large data set of videos with posed and natural facial expressions. In the experiments, we compare the action units detected by our approach with annotations made by human FACS annotators. Our results show that the agreement between the system and human FACS annotators is higher than 90% and underlines the potential of modern computer vision and machine learning techniques to social psychology research. We conclude with some suggestions on how systems like ours can play an important role in research on social signals. PMID:21989609

  14. 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. PMID:23774164

  15. The Behavioral Actions of Lithium in Rodent Models

    PubMed Central

    O’Donnell, Kelley C.; Gould, Todd D.

    2007-01-01

    For nearly as long as lithium has been in clinical use for the treatment of bipolar disorder, depression, and other conditions, investigators have attempted to characterize its effects on behaviors in rodents. Lithium consistently decreases exploratory activity, rearing, aggression, and amphetamine-induced hyperlocomotion; and it increases the sensitivity to pilocarpine-induced seizures, decreases immobility time in the forced swim test, and attenuates reserpine-induced hypolocomotion. Lithium also predictably induces conditioned taste aversion and alterations in circadian rhythms. The modulation of stereotypy, sensitization, and reward behavior are less consistent actions of the drug. These behavioral models may be relevant to human symptoms and to clinical endophenotypes. It is likely that the actions of lithium in a subset of these animal models are related to the therapeutic efficacy, as well the side effects, of the drug. We conclude with a brief discussion of various molecular mechanisms by which these lithium-sensitive behaviors may be mediated, and comment on the ways in which rat and mouse models can be used more effectively in the future to address persistent questions about the therapeutically relevant molecular actions of lithium. PMID:17532044

  16. Action-space Clustering of Tidal Streams to Infer the Galactic Potential

    NASA Astrophysics Data System (ADS)

    Sanderson, Robyn E.; Helmi, Amina; Hogg, David W.

    2015-03-01

    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 data 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.

  17. Monophasic action potential recordings during acute changes in ventricular loading induced by the Valsalva manoeuvre.

    PubMed Central

    Taggart, P; Sutton, P; John, R; Lab, M; Swanton, H

    1992-01-01

    OBJECTIVE--The strong association between ventricular arrhythmia and ventricular dysfunction is unexplained. This study was designed to investigate a mechanism by which a change in ventricular loading could alter the time course of repolarisation and hence refractoriness. A possible mechanism may be a direct effect of an altered pattern of contraction on ventricular repolarisation and hence refractoriness. This relation has been termed contraction-excitation feedback or mechano-electric feedback. METHODS--Monophasic action potentials were recorded from the left ventricular endocardium as a measure of the time course of local repolarisation. The Valsalva manoeuvre was used to change ventricular loading by increasing the intrathoracic pressure and impeding venous return, and hence reducing ventricular pressure and volume (ventricular unloading). PATIENTS--23 patients undergoing routine cardiac catheterisation procedures: seven with no angiographic evidence of abnormal wall motion or history of myocardial infarction (normal), five with a history of myocardial infarction but with normal wall motion, and 10 with angiographic evidence of abnormal wall motion--with or without previous infarction. One patient was a transplant recipient and was analysed separately. SETTING--Tertiary referral centre for cardiology. RESULTS--In patients with normal ventricles during the unloading phase of the Valsalva manoeuvre (mean (SD)) monophasic action potential duration shortened from 311 (47) ms to 295 (47) ms (p less than 0.001). After release of the forced expiration as venous return was restored the monophasic action potential duration lengthened from 285 (44) ms to 304 (44) ms (p less than 0.0001). In the group with evidence of abnormal wall motion the direction of change of action potential duration during the strain phase was normal in 7/21 observations, abnormal in 6/21, and showed no clear change in 8/21. During the release phase 11/20 observations were normal, five abnormal

  18. Recording Single Neurons' Action Potentials from Freely Moving Pigeons Across Three Stages of Learning

    PubMed Central

    Güntürkün, Onur

    2014-01-01

    While the subject of learning has attracted immense interest from both behavioral and neural scientists, only relatively few investigators have observed single-neuron activity while animals are acquiring an operantly conditioned response, or when that response is extinguished. But even in these cases, observation periods usually encompass only a single stage of learning, i.e. acquisition or extinction, but not both (exceptions include protocols employing reversal learning; see Bingman et al.1 for an example). However, acquisition and extinction entail different learning mechanisms and are therefore expected to be accompanied by different types and/or loci of neural plasticity. Accordingly, we developed a behavioral paradigm which institutes three stages of learning in a single behavioral session and which is well suited for the simultaneous recording of single neurons' action potentials. Animals are trained on a single-interval forced choice task which requires mapping each of two possible choice responses to the presentation of different novel visual stimuli (acquisition). After having reached a predefined performance criterion, one of the two choice responses is no longer reinforced (extinction). Following a certain decrement in performance level, correct responses are reinforced again (reacquisition). By using a new set of stimuli in every session, animals can undergo the acquisition-extinction-reacquisition process repeatedly. Because all three stages of learning occur in a single behavioral session, the paradigm is ideal for the simultaneous observation of the spiking output of multiple single neurons. We use pigeons as model systems, but the task can easily be adapted to any other species capable of conditioned discrimination learning. PMID:24961391

  19. Baby Skyrme models without a potential term

    NASA Astrophysics Data System (ADS)

    Ashcroft, Jennifer; Haberichter, Mareike; Krusch, Steffen

    2015-05-01

    We develop a one-parameter family of static baby Skyrme models that do not require a potential term to admit topological solitons. This is a novel property as the standard baby Skyrme model must contain a potential term in order to have stable soliton solutions, though the Skyrme model does not require this. Our new models satisfy an energy bound that is linear in terms of the topological charge and can be saturated in an extreme limit. They also satisfy a virial theorem that is shared by the Skyrme model. We calculate the solitons of our new models numerically and observe that their form depends significantly on the choice of parameter. In one extreme, we find compactons while at the other there is a scale invariant model in which solitons can be obtained exactly as solutions to a Bogomolny equation. We provide an initial investigation into these solitons and compare them with the baby Skyrmions of other models.

  20. COST Action FP1005 ``Fibre suspension flow modelling''

    NASA Astrophysics Data System (ADS)

    Marchioli, Cristian

    2013-11-01

    Fibre suspensions are extremely complex solid-liquid systems since their components (fibres, flocs, air bubbles and additives) interact mutually in a complex way. The dynamics of fibre suspensions are crucial in many real-life applications, such as pulp and paper production. Current understanding of suspension flow dynamics remains poor and incomplete, resulting in conservative design of industrial equipments, low energy efficiency and equipment oversizing. In this paper, the most recent advancements in modelling and experimentation of fibre suspensions dynamics are presented. These advancements have been obtained in the framework of Action FP1005, funded by the COST Programme (European Cooperation in Science and Technology) to coordinate nationally-funded research on a European level. The Action aims at developing and validating numerical models for prediction of fibre suspensions as well as measurement techniques. The Action offers a forum to solve test cases and to compare simulated results to experiments, resulting in more reliable simulation tools to industry. Successfull introduction of such tool into industrial practice is crucial to innovate and increase competitivity of papermaking industry.

  1. Reputation and Competition in a Hidden Action Model

    PubMed Central

    Fedele, Alessandro; Tedeschi, Piero

    2014-01-01

    The economics models of reputation and quality in markets can be classified in three categories. (i) Pure hidden action, where only one type of seller is present who can provide goods of different quality. (ii) Pure hidden information, where sellers of different types have no control over product quality. (iii) Mixed frameworks, which include both hidden action and hidden information. In this paper we develop a pure hidden action model of reputation and Bertrand competition, where consumers and firms interact repeatedly in a market with free entry. The price of the good produced by the firms is contractible, whilst the quality is noncontractible, hence it is promised by the firms when a contract is signed. Consumers infer future quality from all available information, i.e., both from what they know about past quality and from current prices. According to early contributions, competition should make reputation unable to induce the production of high-quality goods. We provide a simple solution to this problem by showing that high quality levels are sustained as an outcome of a stationary symmetric equilibrium. PMID:25329387

  2. Reputation and competition in a hidden action model.

    PubMed

    Fedele, Alessandro; Tedeschi, Piero

    2014-01-01

    The economics models of reputation and quality in markets can be classified in three categories. (i) Pure hidden action, where only one type of seller is present who can provide goods of different quality. (ii) Pure hidden information, where sellers of different types have no control over product quality. (iii) Mixed frameworks, which include both hidden action and hidden information. In this paper we develop a pure hidden action model of reputation and Bertrand competition, where consumers and firms interact repeatedly in a market with free entry. The price of the good produced by the firms is contractible, whilst the quality is noncontractible, hence it is promised by the firms when a contract is signed. Consumers infer future quality from all available information, i.e., both from what they know about past quality and from current prices. According to early contributions, competition should make reputation unable to induce the production of high-quality goods. We provide a simple solution to this problem by showing that high quality levels are sustained as an outcome of a stationary symmetric equilibrium. PMID:25329387

  3. NURSE ASSISTANT MENTAL MODELS, SENSING MAKING, CARE ACTIONS AND CONSEQUENCES FOR NURSING HOME RESIDENTS

    PubMed Central

    Anderson, Ruth A.; Ammarell, Natalie; Bailey, Donald; Colóon-Emeric, Cathleen; Corazzini, Kirsten N.; Lillie, Melissa; Scotton Piven, Mary Lynn; Utley-Smith, Queen; McDaniel, Reuben R.

    2005-01-01

    In a nursing home case study using observation and interview data, we described two mental models that guided certified nurse assistants (CNAs) in resident care. The Golden Rule guided CNAs to respond to residents as they would want someone to do for them. Mother wit guided CNAs to treat residents as they would treat their own children. These mental models engendered self-control and affection. We found limits to the models in that they led to actions such as infantalization and misinterpretations about potentially undiagnosed conditions such as depression or pain. Further, we found that CNAs were isolated from clinicians; little resident information was exchanged. We suggest ways to alter CNA mental models to give them a better basis for action and strategies for connecting CNAs and clinical professionals to improve information flow about residents. Study results highlight a critical need for registered nurses (RNs) to be involved in frontline care. PMID:16221876

  4. {sup 4}He microscopic optical model potential

    SciTech Connect

    Guo Hairui; Liang Haiying; Han Yinlu; Shen Qingbiao; Xu Yongli

    2011-06-15

    The {sup 4}He microscopic optical model potential is obtained by Green's function method through nuclear matter approximation and local density approximation based on the effective Skyrme interaction. The microscopic optical model potential is analyzed and utilized to calculate the reaction cross sections and elastic scattering angular distributions for the target nuclei in the mass range 12{<=}A{<=}209 with incident {sup 4}He energy up to 400 MeV. The theoretical results are compared with the experimental data.

  5. 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

  6. Cycles of Action through Systems of Activity: Examining an Action Research Model through the Lens of Activity Theory

    ERIC Educational Resources Information Center

    Orland-Barak, Lily; Becher, Ayelet

    2011-01-01

    In this article we offer an extended reading of an action research model in the context of mentored learning in preservice education in Israel. Our reading attends both to how a particular form of action research plays out in participants' constructions of the practice of mentoring and mentored learning and how such constructions can be understood…

  7. Scalar Potential Model of photon diffraction

    NASA Astrophysics Data System (ADS)

    Hodge, John

    2011-04-01

    Some observations of light are inconsistent with a wave-like model. Other observations of light are inconsistent with a traditional particle-like model. A single model of light has remained a mystery. Newton's speculations, Democritus's speculations, the Bohm interpretation, and the fractal philosophy are combined with the cosmological Scalar Potential Model (SPM). The resulting model of photon structure and dynamics is tested by a toy computer experiment. The simulations included light from a distance and Young's experiment. The patterns on the screens showed diffraction wave patterns fit by the Fresnel equation. The model is consistent with the Afshar experiment and with the concepts of Bohmian mechanics.

  8. Modeling the Gabaergic Action of Etomidate on the Thalamocortical System

    PubMed Central

    Talavera, Jason A.; Esser, Steven K.; Amzica, Florin; Hill, Sean; Antognini, Joseph F.

    2008-01-01

    Background We have used a computational model of the thalamocortical system to investigate the effects of a GABAergic anesthetic (etomidate) on cerebral cortical and thalamic neuronal function. We examined the effects of phasic and tonic inhibition, as well as the relative importance of anesthetic action in the thalamus and cortex. Methods The amount of phasic GABAergic inhibition was adjusted in the model to simulate etomidate concentrations of between 0.25 and 2 μM, with the concentration range producing unconsciousness assumed to be between 0.25-0.5 μM. In addition, we modeled tonic inhibition separately, and then phasic and tonic inhibition together. We also introduced phasic and tonic inhibition into the cerebral cortex and thalamus separately to determine the relative importance of each of these structures to anesthetic-induced depression of the thalamocortical system. Results Phasic inhibition decreased cortical neuronal firing by 11-18% in the 0.25-0.5 μM range and by 38% at 2 μM. Tonic inhibition produced similar depression (11-21%) in the 0.25-0.5 μM range but 65% depression at 2 μM; phasic and tonic inhibition combined produced the most inhibition (76% depression at 2 μM). When the thalamus and cortex were separately subjected to phasic and tonic inhibition, cortical firing rates decreased less compared to when both structures were targeted. In the 0.25-0.5 μM range, cortical firing rate was minimally affected when etomidate action was simulated in the thalamus only. Conclusions This computational model of the thalamocortical system indicated that tonic GABAergic inhibition appears to be more important than phasic GABAergic inhibition (especially at larger etomidate concentrations), although both combined had the most effect on cerebral cortical firing rates. Furthermore, etomidate action in the thalamus, by itself, does not likely explain etomidate-induced unconsciousness. PMID:19095844

  9. Effects of bath resistance on action potentials in the squid giant axon: myocardial implications.

    PubMed Central

    Wu, J; Wikswo, J P

    1997-01-01

    This study presents a simplified version of the quasi-one-dimensional theory (Wu, J., E. A. Johnson, and J. M. Kootsey. 1996. A quasi-one-dimensional theory for anisotropic propagation of excitation in cardiac muscle. Biophys. J. 71:2427-2439) with two components of the extracellular current, along and perpendicular to the axis, and a simulation and its experimental confirmation for the giant axon of the squid. By extending the one-dimensional core conductor cable equations, this theory predicts, as confirmed by the experiment, that the shapes of the intracellular and the extracellular action potentials are related to the resistance of the bath. Such a result was previously only expected by the field theories. The correlation between the shapes of the intracellular and the extracellular potentials of the giant axon of the squid resembles that observed during the anisotropic propagation of excitation in cardiac muscle. Therefore, this study not only develops a quasi-one-dimensional theory for a squid axon, but also provides one possible factor contributing to the anisotropic propagation of action potentials in cardiac muscle. PMID:9370430

  10. 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

  11. Phase Relationship between Alternans of Early and Late Phases of Ventricular Action Potentials

    PubMed Central

    Jing, Linyuan; Agarwal, Anuj; Chourasia, Sonam; Patwardhan, Abhijit

    2012-01-01

    Background: Alternans of early phase and of duration of action potential (AP) critically affect dispersion of refractoriness through their influence on conduction and repolarization. We investigated the phase relationship between the two alternans and its effect on conduction. Methods and Results: Transmembrane potentials recorded from ventricles of eight swine and three canines during paced activation intervals of ≤300 ms were used to quantify alternans of maximum rate of depolarization (|dv/dt|max) and of action potential duration (APD). Incidence of APD alternans was 62 and 76% in swine and canines. Alternans of APD was frequently accompanied with alternans of |dv/dt|max. Of these, 4 and 26% were out of phase in swine and canines, i.e., low |dv/dt|max preceded long APD. Computer simulations show that out of phase alternans attenuate variation of wavelength and thus minimize formation of spatially discordant alternans. Conclusion: The spontaneous switching of phase relationship between alternans of depolarization and repolarization suggests that mechanisms underlying these alternans may operate independent of each other. The phase between these alternans can critically impact spatial dispersion of refractoriness and thus stability of conduction, with the in phase relation promoting transition from concord to discord while out of phase preventing formation of discord. PMID:22701104

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

    PubMed Central

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

    2014-01-01

    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, ultra-conformable, biocompatible and scalable neural interface array (the ‘NeuroGrid’) that can record both LFP 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 isolation of putative single neurons in rats. Spiking activity demonstrated consistent phase modulation by ongoing brain oscillations and was stable in recordings exceeding one week. We also recorded LFP-modulated spiking activity intra-operatively 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. PMID:25531570

  13. In vivo neuronal action potential recordings via three-dimensional microscale needle-electrode arrays

    PubMed Central

    Fujishiro, Akifumi; Kaneko, Hidekazu; Kawashima, Takahiro; Ishida, Makoto; Kawano, Takeshi

    2014-01-01

    Very fine needle-electrode arrays potentially offer both low invasiveness and high spatial resolution of electrophysiological neuronal recordings in vivo. Herein we report the penetrating and recording capabilities of silicon-growth-based three-dimensional microscale-diameter needle-electrodes arrays. The fabricated needles exhibit a circular-cone shape with a 3-μm-diameter tip and a 210-μm length. Due to the microscale diameter, our silicon needles are more flexible than other microfabricated silicon needles with larger diameters. Coating the microscale-needle-tip with platinum black results in an impedance of ~600 kΩ in saline with output/input signal amplitude ratios of more than 90% at 40 Hz–10 kHz. The needles can penetrate into the whisker barrel area of a rat's cerebral cortex, and the action potentials recorded from some neurons exhibit peak-to-peak amplitudes of ~300 μVpp. These results demonstrate the feasibility of in vivo neuronal action potential recordings with a microscale needle-electrode array fabricated using silicon growth technology. PMID:24785307

  14. In vivo neuronal action potential recordings via three-dimensional microscale needle-electrode arrays

    NASA Astrophysics Data System (ADS)

    Fujishiro, Akifumi; Kaneko, Hidekazu; Kawashima, Takahiro; Ishida, Makoto; Kawano, Takeshi

    2014-05-01

    Very fine needle-electrode arrays potentially offer both low invasiveness and high spatial resolution of electrophysiological neuronal recordings in vivo. Herein we report the penetrating and recording capabilities of silicon-growth-based three-dimensional microscale-diameter needle-electrodes arrays. The fabricated needles exhibit a circular-cone shape with a 3-μm-diameter tip and a 210-μm length. Due to the microscale diameter, our silicon needles are more flexible than other microfabricated silicon needles with larger diameters. Coating the microscale-needle-tip with platinum black results in an impedance of ~600 kΩ in saline with output/input signal amplitude ratios of more than 90% at 40 Hz-10 kHz. The needles can penetrate into the whisker barrel area of a rat's cerebral cortex, and the action potentials recorded from some neurons exhibit peak-to-peak amplitudes of ~300 μVpp. These results demonstrate the feasibility of in vivo neuronal action potential recordings with a microscale needle-electrode array fabricated using silicon growth technology.

  15. In vivo neuronal action potential recordings via three-dimensional microscale needle-electrode arrays.

    PubMed

    Fujishiro, Akifumi; Kaneko, Hidekazu; Kawashima, Takahiro; Ishida, Makoto; Kawano, Takeshi

    2014-01-01

    Very fine needle-electrode arrays potentially offer both low invasiveness and high spatial resolution of electrophysiological neuronal recordings in vivo. Herein we report the penetrating and recording capabilities of silicon-growth-based three-dimensional microscale-diameter needle-electrodes arrays. The fabricated needles exhibit a circular-cone shape with a 3-μm-diameter tip and a 210-μm length. Due to the microscale diameter, our silicon needles are more flexible than other microfabricated silicon needles with larger diameters. Coating the microscale-needle-tip with platinum black results in an impedance of ~600 kΩ in saline with output/input signal amplitude ratios of more than 90% at 40 Hz-10 kHz. The needles can penetrate into the whisker barrel area of a rat's cerebral cortex, and the action potentials recorded from some neurons exhibit peak-to-peak amplitudes of ~300 μVpp. These results demonstrate the feasibility of in vivo neuronal action potential recordings with a microscale needle-electrode array fabricated using silicon growth technology. PMID:24785307

  16. Monophasic action potentials and Ca2+ transients in ischaemically preconditioned rabbit ventricular muscle

    PubMed Central

    Dekker, L.R.C.; van Bavel, E.; Opthof, T.; Coronel, R.; Janse, M.J.

    2003-01-01

    Background ATP-sensitive K+ (KATP) channels play an important role in the protective mechanism underlying ischaemic preconditioning. Ample evidence indicates, however, that action potential shortening is not a prerequisite for the cardioprotective effect of preconditioning. Methods Monophasic action potential duration (MAPD), tissue resistance, intracellular Ca2+ (Indo-1) and mechanical activity were simultaneously assessed in arterially perfused rabbit papillary muscles. We studied four experimental protocols preceding sustained ischaemia: 1. control perfusion (n=6), 2. ischaemic preconditioning (PC; n=4), 3. pretreatment with a KATP channel blocker, glibenclamide (15 μmol/1), prior to ischaemic preconditioning (PC+glib; n=3), 4. glibenclamide pretreatment only (Glib; n=2). Results In the PC group an increase in the diastolic Ca2+ level and a prolongation of the Ca2+ transient just prior to the induction of sustained ischaemia correlate to the postponement of the onset of irreversible ischaemic damage, as established by a rise in [Ca2+]i, electrical uncoupling and contracture. Glibenclamide antagonised these changes in the Ca2+ transient and the cardioprotection induced by preconditioning. MAPD was equal in all experimental groups. Conclusions Prolongation of the Ca2+ transient and increase of diastolic [Ca2+]i just prior to the induction of sustained ischaemia and not action potential shortening are involved in the cardioprotective effect of ischaemic preconditioning. Therefore, a glibenclamide-sensitive mechanism, other than the sarcolemmal KATP channels, is involved in the protective effect of ischaemic preconditioning. Changes in Ca2+ metabolism may play a crucial role in ischaemic preconditioning. ImagesFigure 1 PMID:25696182

  17. Generation of slow wave type action potentials in the mouse small intestine involves a non-L-type calcium channel.

    PubMed

    Malysz, J; Richardson, D; Farraway, L; Christen, M O; Huizinga, J D

    1995-10-01

    Intrinsic electrical activities in various isolated segments of the mouse small intestine were recorded (i) to characterize action potential generation and (ii) to obtain a profile on the ion channels involved in initiating the slow wave type action potentials (slow waves). Gradients in slow wave frequency, resting membrane potential, and occurrence of spiking activity were found, with the proximal intestine exhibiting the highest frequency, the most hyperpolarized cell membrane, and the greatest occurrence of spikes. The slow waves were only partially sensitive to L-type calcium channel blockers. Nifedipine, verapamil, and pinaverium bromide abolished spikes that occurred on the plateau phase of the slow waves in all tissues. The activity that remained in the presence of L-type calcium channel blockers, the upstroke potential, retained a similar amplitude to the original slow wave and was of identical frequency. The upstroke potential was not sensitive to a reduction in extracellular chloride or to the sodium channel blockers tetrodotoxin and mexiletine. Abolishment of the Na+ gradient by removal of 120 mM extracellular Na+ reduced the upstroke potential frequency by 13 - 18% and its amplitude by 50 - 70% in the ileum. The amplitude was similarly reduced by Ni2+ (up to 5 mM), and by flufenamic acid (100 mu M), a nonspecific cation and chloride channel blocker. Gadolinium, a nonspecific blocker of cation and stretch-activated channels, had no effect. Throughout these pharmacological manipulations, a robust oscillation remained at 5 - 10 mV. This oscillation likely reflects pacemaker activity. It was rapidly abolished by removal of extracellular calcium but not affected by L-type calcium channel blockers. In summary, the mouse small intestine has been established as a model for research into slow wave generation and electrical pacemaker activity. The upstroke part of the slow wave has two components, the pacemaker component involves a non-L-type calcium channel

  18. A dynamic appearance descriptor approach to facial actions temporal modeling.

    PubMed

    Jiang, Bihan; Valstar, Michel; Martinez, Brais; Pantic, Maja

    2014-02-01

    Both the configuration and the dynamics of facial expressions are crucial for the interpretation of human facial behavior. Yet to date, the vast majority of reported efforts in the field either do not take the dynamics of facial expressions into account, or focus only on prototypic facial expressions of six basic emotions. Facial dynamics can be explicitly analyzed by detecting the constituent temporal segments in Facial Action Coding System (FACS) Action Units (AUs)-onset, apex, and offset. In this paper, we present a novel approach to explicit analysis of temporal dynamics of facial actions using the dynamic appearance descriptor Local Phase Quantization from Three Orthogonal Planes (LPQ-TOP). Temporal segments are detected by combining a discriminative classifier for detecting the temporal segments on a frame-by-frame basis with Markov Models that enforce temporal consistency over the whole episode. The system is evaluated in detail over the MMI facial expression database, the UNBC-McMaster pain database, the SAL database, the GEMEP-FERA dataset in database-dependent experiments, in cross-database experiments using the Cohn-Kanade, and the SEMAINE databases. The comparison with other state-of-the-art methods shows that the proposed LPQ-TOP method outperforms the other approaches for the problem of AU temporal segment detection, and that overall AU activation detection benefits from dynamic appearance information. PMID:23757539

  19. Electrophysiological properties of rat spinal dorsal horn neurones in vitro: calcium-dependent action potentials.

    PubMed Central

    Murase, K; Randić, M

    1983-01-01

    1. The electrophysiological properties of dorsal horn neurones have been investigated in the immature rat in vitro spinal cord slice preparation. 2. Intracellular recordings from dorsal horn neurones show that direct or orthodromic stimulation generates action potentials followed by a brief after-hyperpolarization. Synaptic potentials were elicited by the activation of primary afferent fibres in the dorsal root. 3. Input resistance for dorsal horn neurones ranged from 48 to 267 M omega, and the membrane time constant was in the range of 4-19 ms. 4. In response to strong depolarizing currents dorsal horn neurones perfused with TTX and TEA frequently exhibit a slow regenerative depolarizing potential followed by a slow after-hyperpolarization. The depolarizing potential probably results from an influx of Ca. It is blocked by low concentration Ca, Co or Mn, and enhanced by high levels of extracellular Ca. 5. There is, in addition, a low-threshold Ca-dependent response which is activated at membrane potentials more negative than -65 mV and has a maximum rate of rise at the polarization level of about -80 mV. 6. The addition of Ba or TEA to the perfusing medium provided support for the Ca-dependence of the low- and high-threshold responses, and the lack of fast inactivation of the high-threshold Ca potential. Images Plate 1 PMID:6306228

  20. Dynamical speckles patterns of action potential transmission effects in squid giant axon membrane

    NASA Astrophysics Data System (ADS)

    Llovera-González, Juan J.; Moreno-Yeras, Alfredo B.; Muramatsu, Mikiya; Soga, Diogo; Serra-Toledo, Rolando L.; Magalhães, Daniel S. F.

    2013-11-01

    Undoubtedly the most important result of the investigations in physiology and biophysics was the discovery of the electrochemical mechanism of propagation of the action potential in nerves that was made by Hodgkin and Huxley during the first half of the past century. Since some decades ago diverse experiments about the electro optical properties of the axon membrane there was published using the most diverse optical experimental procedures6-10. In this paper some results of a dynamical speckle technique applied for obtaining microscopic images of a section of a squid giant axon membrane during the activation by electrical impulses and his digital process are presented.

  1. Linking knowledge and action through mental models of sustainable agriculture.

    PubMed

    Hoffman, Matthew; Lubell, Mark; Hillis, Vicken

    2014-09-01

    Linking knowledge to action requires understanding how decision-makers conceptualize sustainability. This paper empirically analyzes farmer "mental models" of sustainability from three winegrape-growing regions of California where local extension programs have focused on sustainable agriculture. The mental models are represented as networks where sustainability concepts are nodes, and links are established when a farmer mentions two concepts in their stated definition of sustainability. The results suggest that winegrape grower mental models of sustainability are hierarchically structured, relatively similar across regions, and strongly linked to participation in extension programs and adoption of sustainable farm practices. We discuss the implications of our findings for the debate over the meaning of sustainability, and the role of local extension programs in managing knowledge systems. PMID:25157158

  2. Continuous human action recognition using depth-MHI-HOG and a spotter model.

    PubMed

    Eum, Hyukmin; Yoon, Changyong; Lee, Heejin; Park, Mignon

    2015-01-01

    In this paper, we propose a new method for spotting and recognizing continuous human actions using a vision sensor. The method is comprised of depth-MHI-HOG (DMH), action modeling, action spotting, and recognition. First, to effectively separate the foreground from background, we propose a method called DMH. It includes a standard structure for segmenting images and extracting features by using depth information, MHI, and HOG. Second, action modeling is performed to model various actions using extracted features. The modeling of actions is performed by creating sequences of actions through k-means clustering; these sequences constitute HMM input. Third, a method of action spotting is proposed to filter meaningless actions from continuous actions and to identify precise start and end points of actions. By employing the spotter model, the proposed method improves action recognition performance. Finally, the proposed method recognizes actions based on start and end points. We evaluate recognition performance by employing the proposed method to obtain and compare probabilities by applying input sequences in action models and the spotter model. Through various experiments, we demonstrate that the proposed method is efficient for recognizing continuous human actions in real environments. PMID:25742172

  3. Flavonoids: a review of probable mechanisms of action and potential applications.

    PubMed

    Nijveldt, R J; van Nood, E; van Hoorn, D E; Boelens, P G; van Norren, K; van Leeuwen, P A

    2001-10-01

    The aim of this review, a summary of the putative biological actions of flavonoids, was to obtain a further understanding of the reported beneficial health effects of these substances. Flavonoids occur naturally in fruit, vegetables, and beverages such as tea and wine. Research in the field of flavonoids has increased since the discovery of the French paradox,ie, the low cardiovascular mortality rate observed in Mediterranean populations in association with red wine consumption and a high saturated fat intake. Several other potential beneficial properties of flavonoids have since been ascertained. We review the different groups of known flavonoids, the probable mechanisms by which they act, and the potential clinical applications of these fascinating natural substances. PMID:11566638

  4. Pharmacological and biochemical actions of simple coumarins: natural products with therapeutic potential.

    PubMed

    Hoult, J R; Payá, M

    1996-06-01

    1. More than 300 coumarins have been identified from natural sources, especially green plants. The pharmacological and biochemical properties and therapeutic applications of simple coumarins depend upon the pattern of substitution. More complex related compounds based on the coumarin nucleus include the dicoumarol/warfarin anticoagulants, aflatoxins and the psoralens (photosensitizing agents). 2. Coumarin itself (1,2-benzopyrone) has long-established efficacy in slow-onset long-term reduction of lymphoedema in man, as confirmed in recent double-blind trials against elephantiasis and postmastectomy swelling of the arm. The mechanism of action is uncertain, but may involve macrophage-induced proteolysis of oedema protein. However, coumarin has low absolute bioavailability in man (< 5%), due to extensive first-pass hepatic conversion to 7-hydroxycoumarin followed by glucuronidation. It may, therefore, be a prodrug. 3. Scoparone (6,7-dimethoxycoumarin) has been purified from the hypolipidaemic Chinese herb Artemisia scoparia and shown to reduce the proliferative responses of human peripheral mononuclear cells, to relax smooth muscle, to reduce total cholesterol and triglycerides and to retard the characteristic pathomorphological changes in hypercholesterolaemic diabetic rabbits. Various properties of scoparone were suggested to account for these findings, including ability to scavenge reactive oxygen species, inhibition of tyrosine kinases and potentiation of prostaglandin generation. 4. Osthole (7-methoxy-8-[3-methylpent-2-enyl]coumarin) from Angelica pubescens, used also in Chinese medicine, causes hypotension in vivo, and inhibits platelet aggregation and smooth muscle contraction in vitro. It may interfere with calcium influx and with cyclic nucleotide phosphodiesterases. 5. Cloricromene, a synthetic coumarin derivative, also possesses antithrombotic antiplatelet actions, inhibits PMN neutrophil function and causes vasodilatation. Some of these properties of

  5. Action of hallucinogens on raphe-evoked dorsal root potentials (DRPs) in the cat.

    PubMed

    Larson, A A; Anderson, E G

    1986-02-01

    The dorsal root potential (DRP) evoked by stimulation of the inferior central nucleus (ICN) of the cat is affected by administration of a variety of hallucinogenic agents. It has been previously shown that a single low dose of LSD is unique in that it potentiates this DRP, while injections of 5-methoxy-N,N- dimethyltryptamine (5-MeODMT), ketamine or phencyclidine (PCP) inhibit its production. Tolerance develops to the facilitatory effect of low doses of LSD on the DRP, but not to the inhibitory action of 5-MeODMT. Repeated injections of ketamine every 30 minutes also fail to produce tachyphylaxis to the inhibitory effect of this dissociative anesthetic. The raphe-evoked DRP is a long latency potential that is inhibited by a wide variety of putative serotonin antagonists and has therefore been traditionally thought to be mediated by serotonin. However, in light of the inability of either tryptophan or fluoxetine to potentiate this DRP, and the resistance of this DRP to blockade by parachlorophenylalanine, reserpine or intrathecally administered 5,7-dihydroxytryptamine, it appears that this potential may in fact be mediated, at least in part, by a non-serotonergic transmitter. PMID:3952125

  6. Interactions of ethanol and quinidine on contractility and myocyte action potential in the rat ventricle.

    PubMed

    Guthrie, S K; Wilde, D W; Brown, R A; Savage, A O; Bleske, B

    1995-01-01

    The combined effects of ethanol and quinidine on cardiac electromechanical coupling are unknown, but both drugs affect cardiac conduction and can cause myocardial depression. Isolated left ventricular papillary and ventricular myocytes were used to assess the combined effects of quinidine and ethanol on the electrophysiologic and mechanical properties of rat myocardium. The combination of quinidine (1-300 microM) and ethanol (120-240 mg/dL) depressed active papillary muscle tension within the clinically useful concentration range. In electrophysiologic studies of isolated ventricular myocytes, quinidine prolonged the action potential duration at 50% (APD50) and 90% (APD90) repolarization, the absolute refractory period, and the relative refractory period, but decreased the maximum rate of change of depolarization in phase 0 (Vmax). When cells were exposed to ethanol (240 mg/dL) and quinidine (1.5 microM) together, a significant decrease in the quinidine-induced prolongation of the absolute refractory and relative refractory periods was seen. Additional changes in action potential parameters from the quinidine values included slight reductions in Vmax and in APD50 and APD90, but these reductions were not consistently displayed, nor were they statistically significant. PMID:7897336

  7. Biorealistic cardiac cell culture platforms with integrated monitoring of extracellular action potentials

    PubMed Central

    Trantidou, Tatiana; Terracciano, Cesare M.; Kontziampasis, Dimitrios; Humphrey, Eleanor J.; Prodromakis, Themistoklis

    2015-01-01

    Current platforms for in vitro drug development utilize confluent, unorganized monolayers of heart cells to study the effect on action potential propagation. However, standard cell cultures are of limited use in cardiac research, as they do not preserve important structural and functional properties of the myocardium. Here we present a method to integrate a scaffolding technology with multi-electrode arrays and deliver a compact, off-the-shelf monitoring platform for growing biomimetic cardiac tissue. Our approach produces anisotropic cultures with conduction velocity (CV) profiles that closer resemble native heart tissue; the fastest impulse propagation is along the long axis of the aligned cardiomyocytes (CVL) and the slowest propagation is perpendicular (CVT), in contrast to standard cultures where action potential propagates isotropically (CVL ≈ CVT). The corresponding anisotropy velocity ratios (CVL/CVT = 1.38 – 2.22) are comparable with values for healthy adult rat ventricles (1.98 – 3.63). The main advantages of this approach are that (i) it provides ultimate pattern control, (ii) it is compatible with automated manufacturing steps and (iii) it is utilized through standard cell culturing protocols. Our platform is compatible with existing read-out equipment and comprises a prompt method for more reliable CV studies. PMID:26053434

  8. Supernormal Conduction and Suppression of Spatially Discordant Alternans of Cardiac Action Potentials

    PubMed Central

    Jing, Linyuan; Agarwal, Anuj; Patwardhan, Abhijit

    2016-01-01

    Spatially discordant alternans (DA) of action potential durations (APD) is thought to be more pro-arrhythmic than concordant alternans. Super normal conduction (SNC) has been reported to suppress formation of DA. An increase in conduction velocity (CV) as activation rate increases, i.e., a negative CV restitution, is widely considered as hallmark of SNC. Our aim in this study is to show that it is not an increase in CV for faster rates that prevents formation of DA, rather, it is the ratio of the CV for the short relative to the long activation that is critical in DA suppression. To illustrate this subtlety, we simulated this phenomenon using two approaches; (1) by using the standard, i.e., S1S2 protocol to quantify restitution and disabling the slow inactivation gate j of the sodium current (INa), and (2) by using the dynamic, i.e., S1S1 protocol for quantification of restitution and increasing INa at different cycle lengths (CL). Even though both approaches produced similar CV restitution curves, DA was suppressed only during the first approach, where the CV of the short of the long-short action potential (AP) pattern was selectively increased. These results show that negative CV restitution, which is considered characteristic of SNC, per se, is not causal in suppressing DA, rather, the critical factor is a change in the ratio of the velocities of the short and the long APs. PMID:26779035

  9. 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. PMID:26817404

  10. Peripheral Hot Spots for Local Ca2+ Release after Single Action Potentials in Sympathetic Ganglion Neurons

    PubMed Central

    Cseresnyés, Zoltán; Schneider, Martin F.

    2004-01-01

    Ca2+ release from the endoplasmic reticulum (ER) contributes to Ca2+ transients in frog sympathetic ganglion neurons. Here we use video-rate confocal fluo-4 fluorescence imaging to show that single action potentials reproducibly trigger rapidly rising Ca2+ transients at 1–3 local hot spots within the peripheral ER-rich layer in intact neurons in fresh ganglia and in the majority (74%) of cultured neurons. Hot spots were located near the nucleus or the axon hillock region. Other regions exhibited either slower and smaller signals or no response. Ca2+ signals spread into the cell at constant velocity across the ER in nonnuclear regions, indicating active propagation, but spread with a (time)1/2 dependence within the nucleus, consistent with diffusion. 26% of cultured cells exhibited uniform Ca2+ signals around the periphery, but hot spots were produced by loading the cytosol with EGTA or by bathing such cells in low-Ca2+ Ringer's solution. Peripheral hot spots for Ca2+ release within the perinuclear and axon hillock regions provide a mechanism for preferential initiation of nuclear and axonal Ca2+ signals by single action potentials in sympathetic ganglion neurons. PMID:14695260

  11. 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

  12. Spectral action for Bianchi type-IX cosmological models

    NASA Astrophysics Data System (ADS)

    Fan, Wentao; Fathizadeh, Farzad; Marcolli, Matilde

    2015-10-01

    A rationality result previously proved for Robertson-Walker metrics is extended to a homogeneous anisotropic cosmological model, namely the Bianchi type-IX minisuperspace. It is shown that the Seeley-de Witt coefficients appearing in the expansion of the spectral action for the Bianchi type-IX geometry are expressed in terms of polynomials with rational coefficients in the cosmic evolution factors w 1( t) , w 2( t) , w 3( t) , and their higher derivates with respect to time. We begin with the computation of the Dirac operator of this geometry and calculate the coefficients a 0 ,a 2 ,a 4 of the spectral action by using heat kernel methods and parametric pseudodifferential calculus. An efficient method is devised for computing the Seeley-de Witt coefficients of a geometry by making use of Wodzicki's noncommutative residue, and it is confirmed that the method checks out for the cosmological model studied in this article. The advantages of the new method are discussed, which combined with symmetries of the Bianchi type-IX metric, yield an elegant proof of the rationality result.

  13. Synchronized action of synaptically coupled chaotic model neurons.

    PubMed

    Abarbanel, H D; Huerta, R; Rabinovich, M I; Rulkov, N F; Rowat, P F; Selverston, A I

    1996-11-15

    Experimental observations of the intracellular recorded electrical activity in individual neurons show that the temporal behavior is often chaotic. We discuss both our own observations on a cell from the stomatogastric central pattern generator of lobster and earlier observations in other cells. In this paper we work with models with chaotic neurons, building on models by Hindmarsh and Rose for bursting, spiking activity in neurons. The key feature of these simplified models of neurons is the presence of coupled slow and fast subsystems. We analyze the model neurons using the same tools employed in the analysis of our experimental data. We couple two model neurons both electrotonically and electrochemically in inhibitory and excitatory fashions. In each of these cases, we demonstrate that the model neurons can synchronize in phase and out of phase depending on the strength of the coupling. For normal synaptic coupling, we have a time delay between the action of one neuron and the response of the other. We also analyze how the synchronization depends on this delay. A rich spectrum of synchronized behaviors is possible for electrically coupled neurons and for inhibitory coupling between neurons. In synchronous neurons one typically sees chaotic motion of the coupled neurons. Excitatory coupling produces essentially periodic voltage trajectories, which are also synchronized. We display and discuss these synchronized behaviors using two "distance" measures of the synchronization. PMID:8888609

  14. 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

  15. Understanding Vertical Jump Potentiation: A Deterministic Model.

    PubMed

    Suchomel, Timothy J; Lamont, Hugh S; Moir, Gavin L

    2016-06-01

    This review article discusses previous postactivation potentiation (PAP) literature and provides a deterministic model for vertical jump (i.e., squat jump, countermovement jump, and drop/depth jump) potentiation. There are a number of factors that must be considered when designing an effective strength-power potentiation complex (SPPC) focused on vertical jump potentiation. Sport scientists and practitioners must consider the characteristics of the subject being tested and the design of the SPPC itself. Subject characteristics that must be considered when designing an SPPC focused on vertical jump potentiation include the individual's relative strength, sex, muscle characteristics, neuromuscular characteristics, current fatigue state, and training background. Aspects of the SPPC that must be considered for vertical jump potentiation include the potentiating exercise, level and rate of muscle activation, volume load completed, the ballistic or non-ballistic nature of the potentiating exercise, and the rest interval(s) used following the potentiating exercise. Sport scientists and practitioners should design and seek SPPCs that are practical in nature regarding the equipment needed and the rest interval required for a potentiated performance. If practitioners would like to incorporate PAP as a training tool, they must take the athlete training time restrictions into account as a number of previous SPPCs have been shown to require long rest periods before potentiation can be realized. Thus, practitioners should seek SPPCs that may be effectively implemented in training and that do not require excessive rest intervals that may take away from valuable training time. Practitioners may decrease the necessary time needed to realize potentiation by improving their subject's relative strength. PMID:26712510

  16. 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.

  17. Regulation of Action Potential Waveforms by Axonal GABAA Receptors in Cortical Pyramidal Neurons

    PubMed Central

    Xia, Yang; Zhao, Yuan; Yang, Mingpo; Zeng, Shaoqun; Shu, Yousheng

    2014-01-01

    GABAA receptors distributed in somatodendritic compartments play critical roles in regulating neuronal activities, including spike timing and firing pattern; however, the properties and functions of GABAA receptors at the axon are still poorly understood. By recording from the cut end (bleb) of the main axon trunk of layer –5 pyramidal neurons in prefrontal cortical slices, we found that currents evoked by GABA iontophoresis could be blocked by picrotoxin, indicating the expression of GABAA receptors in axons. Stationary noise analysis revealed that single-channel properties of axonal GABAA receptors were similar to those of somatic receptors. Perforated patch recording with gramicidin revealed that the reversal potential of the GABA response was more negative than the resting membrane potential at the axon trunk, suggesting that GABA may hyperpolarize the axonal membrane potential. Further experiments demonstrated that the activation of axonal GABAA receptors regulated the amplitude and duration of action potentials (APs) and decreased the AP-induced Ca2+ transients at the axon. Together, our results indicate that the waveform of axonal APs and the downstream Ca2+ signals are modulated by axonal GABAA receptors. PMID:24971996

  18. External potassium and action potential propagation in rat fast and slow twitch muscles.

    PubMed

    Kössler, F; Lange, F; Caffier, G; Küchler, G

    1991-10-01

    The role of extracellular K+ concentration in the propagation velocity of action potential was tested in isolated rat skeletal muscles. Different K+ concentrations were produced by KCl additions to extracellular solution. Action potentials were measured extracellularly by means of two annular platinum electrodes. Fibre bundles of m. soleus (SOL), m. extensor digitorum longus (EDL), red (SMR) and white (SMW) part of m. sternomastoideus were maximum stimulated. The conduction velocity (c.v.) was calculated from the distance between the electrodes and the time delay of the potentials measured at 22 degrees C. In Tyrode solution containing 5 mmol/l K+, the c.v. was close to 1 m.s-1. Bundles of the fast muscle type seemed to have a somewhat higher c.v. The differences observed in these studies were not significant. At higher temperatures, the c.v. increased (Q10 of approx. 2) and a dissociation between SMR and SMW muscles appeared. An elevation of K+ concentration to 10 mmol/l induced a drop of the c.v. by approx. 25% and 15% in EDL and SOL muscles, respectively. After return to normal solution, the recovery was not complete within 30 min. In K+ free solution the c.v. of EDL and SM muscles rose by a factor of 1.5, but less in SOL muscles. The weaker response of SOL to K+ modification was related to the higher resistance of this muscle to fatigue. This suggestion was supported by experiments on fatigued fibre bundles. Immediately after a tetanic stimulation producing fatigue, the c.v. of EDL and SOL muscles dropped similarly as in 10 mmol/l K+; again, the drop was less for SOL muscles. Adrenaline (0.5-10.0 mumol/l) enhanced both the c.v. and the twitch amplitude. The results support the suggestion that extracellular K+ accumulation during activity is an essential factor of muscle fatigue. PMID:1816028

  19. Modeling the Mass Action Dynamics of Metabolism with Fluctuation Theorems and Maximum Entropy

    NASA Astrophysics Data System (ADS)

    Cannon, William; Thomas, Dennis; Baxter, Douglas; Zucker, Jeremy; Goh, Garrett

    The laws of thermodynamics dictate the behavior of biotic and abiotic systems. Simulation methods based on statistical thermodynamics can provide a fundamental understanding of how biological systems function and are coupled to their environment. While mass action kinetic simulations are based on solving ordinary differential equations using rate parameters, analogous thermodynamic simulations of mass action dynamics are based on modeling states using chemical potentials. The latter have the advantage that standard free energies of formation/reaction and metabolite levels are much easier to determine than rate parameters, allowing one to model across a large range of scales. Bridging theory and experiment, statistical thermodynamics simulations allow us to both predict activities of metabolites and enzymes and use experimental measurements of metabolites and proteins as input data. Even if metabolite levels are not available experimentally, it is shown that a maximum entropy assumption is quite reasonable and in many cases results in both the most energetically efficient process and the highest material flux.

  20. Analytic models of plausible gravitational lens potentials

    SciTech Connect

    Baltz, Edward A.; Marshall, Phil; Oguri, Masamune E-mail: pjm@physics.ucsb.edu

    2009-01-15

    Gravitational lenses on galaxy scales are plausibly modelled as having ellipsoidal symmetry and a universal dark matter density profile, with a Sersic profile to describe the distribution of baryonic matter. Predicting all lensing effects requires knowledge of the total lens potential: in this work we give analytic forms for that of the above hybrid model. Emphasising that complex lens potentials can be constructed from simpler components in linear combination, we provide a recipe for attaining elliptical symmetry in either projected mass or lens potential. We also provide analytic formulae for the lens potentials of Sersic profiles for integer and half-integer index. We then present formulae describing the gravitational lensing effects due to smoothly-truncated universal density profiles in cold dark matter model. For our isolated haloes the density profile falls off as radius to the minus fifth or seventh power beyond the tidal radius, functional forms that allow all orders of lens potential derivatives to be calculated analytically, while ensuring a non-divergent total mass. We show how the observables predicted by this profile differ from that of the original infinite-mass NFW profile. Expressions for the gravitational flexion are highlighted. We show how decreasing the tidal radius allows stripped haloes to be modelled, providing a framework for a fuller investigation of dark matter substructure in galaxies and clusters. Finally we remark on the need for finite mass halo profiles when doing cosmological ray-tracing simulations, and the need for readily-calculable higher order derivatives of the lens potential when studying catastrophes in strong lenses.

  1. Analytic Models of Plausible Gravitational Lens Potentials

    SciTech Connect

    Baltz, Edward A.; Marshall, Phil; Oguri, Masamune

    2007-05-04

    Gravitational lenses on galaxy scales are plausibly modeled as having ellipsoidal symmetry and a universal dark matter density profile, with a Sersic profile to describe the distribution of baryonic matter. Predicting all lensing effects requires knowledge of the total lens potential: in this work we give analytic forms for that of the above hybrid model. Emphasizing that complex lens potentials can be constructed from simpler components in linear combination, we provide a recipe for attaining elliptical symmetry in either projected mass or lens potential.We also provide analytic formulae for the lens potentials of Sersic profiles for integer and half-integer index. We then present formulae describing the gravitational lensing effects due to smoothly-truncated universal density profiles in cold dark matter model. For our isolated haloes the density profile falls off as radius to the minus fifth or seventh power beyond the tidal radius, functional forms that allow all orders of lens potential derivatives to be calculated analytically, while ensuring a non-divergent total mass. We show how the observables predicted by this profile differ from that of the original infinite-mass NFW profile. Expressions for the gravitational flexion are highlighted. We show how decreasing the tidal radius allows stripped haloes to be modeled, providing a framework for a fuller investigation of dark matter substructure in galaxies and clusters. Finally we remark on the need for finite mass halo profiles when doing cosmological ray-tracing simulations, and the need for readily-calculable higher order derivatives of the lens potential when studying catastrophes in strong lenses.

  2. When a Model Needs a Model: Convincing Skeptics of Counterintuitive Results--An Example from Affirmative Action Modeling.

    ERIC Educational Resources Information Center

    Feinberg, William E.

    1988-01-01

    This article describes a monte carlo computer simulation of affirmative action employment policies. The counterintuitive results of the model are explained through a thought device involving urns and marbles. States that such model simulations have implications for social policy. (BSR)

  3. 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

    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

  4. 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

  5. Potential Mechanisms of Action in the Treatment of Social Impairment and Disorganization in Adolescents with ADHD

    PubMed Central

    Evans, Steven W.; Schultz, Brandon K.; Zoromski, Allison K.

    2014-01-01

    Two important domains that can be impaired in adolescents with ADHD are organization and social functioning; however, the development of interventions to target these areas in adolescents is in the early stages. Currently, small efficacy trials are beginning to be used to conduct preliminary tests on the proposed mechanisms of action for these interventions. These two studies examined the efficacy of organization and social functioning interventions for adolescents with ADHD, as well as the potential mechanisms of action for each intervention. Results from the organization intervention provide support for a significant relationship between performance on the organization checklist and overall GPA; however, there was no meaningful pattern of relationships between achieving mastery of the organization tasks and grades within quarter. Further, results from the social functioning intervention support a moderate relationship between performance on process measures of response to the intervention and outcome measures of social functioning. Results of this study provide implications for modifications to the measures and intervention procedures in future research. PMID:24748901

  6. A potential mode of action for Anakinra in patients with arthrofibrosis following total knee arthroplasty

    PubMed Central

    Dixon, David; Coates, Jonathon; del Carpio Pons, Alicia; Horabin, Joanna; Walker, Andrew; Abdul, Nicole; Kalson, Nicholas S.; Brewster, Nigel T.; Weir, David J.; Deehan, David J.; Mann, Derek A.; Borthwick, Lee A.

    2015-01-01

    Arthrofibrosis is a fibroproliferative disease characterised by excessive deposition of extracellular matrix components intra-articularly leading to pain and restricted range of movement. Although frequently observed following total knee arthroplasty (TKA) no therapeutic options exist. A pilot study demonstrated that intra-articular injection of Anakinra, an IL-1R antagonist, improved range of movement and pain in patients with arthrofibrosis however the mechanism of action is unknown. We hypothesise that IL-1α/β will drive an inflammatory phenotype in fibroblasts isolated from the knee, therefore identifying a potential mechanism of action for Anakinra in arthrofibrosis following TKA. Fibroblasts isolated from synovial membranes and infra-patellar fat pad of patients undergoing TKA express high levels of IL-1R1. Stimulation with IL-1α/β induced a pro-inflammatory phenotype characterised by increased secretion of GMCSF, IL-6 and IL-8. No significant difference in the inflammatory response was observed between fibroblasts isolated from synovial membrane or infra-patellar fat pad. IL-1α/β treatments induced a pro-inflammatory phenotype in fibroblasts from both synovial membrane and infra-patellar fat pad and therefore Anakinra can likely have an inhibitory effect on fibroblasts present in both tissues in vivo. It is also likely that fibroblast responses in the tissues are controlled by IL-1α/β availability and not their ability to respond to it. PMID:26553966

  7. Dynamics of action potential firing in electrically connected striatal fast-spiking interneurons

    PubMed Central

    Russo, Giovanni; Nieus, Thierry R.; Maggi, Silvia; Taverna, Stefano

    2013-01-01

    Fast-spiking interneurons (FSIs) play a central role in organizing the output of striatal neural circuits, yet functional interactions between these cells are still largely unknown. Here we investigated the interplay of action potential (AP) firing between electrically connected pairs of identified FSIs in mouse striatal slices. In addition to a loose coordination of firing activity mediated by membrane potential coupling, gap junctions (GJ) induced a frequency-dependent inhibition of spike discharge in coupled cells. At relatively low firing rates (2–20 Hz), some APs were tightly synchronized whereas others were inhibited. However, burst firing at intermediate frequencies (25–60 Hz) mostly induced spike inhibition, while at frequencies >50–60 Hz FSI pairs tended to synchronize. Spike silencing occurred even in the absence of GABAergic synapses or persisted after a complete block of GABAA receptors. Pharmacological suppression of presynaptic spike afterhyperpolarization (AHP) caused postsynaptic spikelets to become more prone to trigger spikes at near-threshold potentials, leading to a mostly synchronous firing activity. The complex pattern of functional coordination mediated by GJ endows FSIs with peculiar dynamic properties that may be critical in controlling striatal-dependent behavior. PMID:24294191

  8. Cancer Driver Log (CanDL): Catalog of Potentially Actionable Cancer Mutations.

    PubMed

    Damodaran, Senthilkumar; Miya, Jharna; Kautto, Esko; Zhu, Eliot; Samorodnitsky, Eric; Datta, Jharna; Reeser, Julie W; Roychowdhury, Sameek

    2015-09-01

    Massively parallel sequencing technologies have enabled characterization of genomic alterations across multiple tumor types. Efforts have focused on identifying driver mutations because they represent potential targets for therapy. However, because of the presence of driver and passenger mutations, it is often challenging to assign the clinical relevance of specific mutations observed in patients. Currently, there are multiple databases and tools that provide in silico assessment for potential drivers; however, there is no comprehensive resource for mutations with functional characterization. Therefore, we created an expert-curated database of potentially actionable driver mutations for molecular pathologists to facilitate annotation of cancer genomic testing. We reviewed scientific literature to identify variants that have been functionally characterized in vitro or in vivo as driver mutations. We obtained the chromosome location and all possible nucleotide positions for each amino acid change and uploaded them to the Cancer Driver Log (CanDL) database with associated literature reference indicating functional driver evidence. In addition to a simple interface, the database allows users to download all or selected genes as a comma-separated values file for incorporation into their own analysis pipeline. Furthermore, the database includes a mechanism for third-party contributions to support updates for novel driver mutations. Overall, this freely available database will facilitate rapid annotation of cancer genomic testing in molecular pathology laboratories for mutations. PMID:26320871

  9. Electrophysiological Motor Unit Number Estimation (MUNE) Measuring Compound Muscle Action Potential (CMAP) in Mouse Hindlimb Muscles.

    PubMed

    Arnold, W David; Sheth, Kajri A; Wier, Christopher G; Kissel, John T; Burghes, Arthur H; Kolb, Stephen J

    2015-01-01

    Compound muscle action potential (CMAP) and motor unit number estimation (MUNE) are electrophysiological techniques that can be used to monitor the functional status of a motor unit pool in vivo. These measures can provide insight into the normal development and degeneration of the neuromuscular system. These measures have clear translational potential because they are routinely applied in diagnostic and clinical human studies. We present electrophysiological techniques similar to those employed in humans to allow recordings of mouse sciatic nerve function. The CMAP response represents the electrophysiological output from a muscle or group of muscles following supramaximal stimulation of a peripheral nerve. MUNE is an electrophysiological technique that is based on modifications of the CMAP response. MUNE is a calculated value that represents the estimated number of motor neurons or axons (motor control input) supplying the muscle or group of muscles being tested. We present methods for recording CMAP responses from the proximal leg muscles using surface recording electrodes following the stimulation of the sciatic nerve in mice. An incremental MUNE technique is described using submaximal stimuli to determine the average single motor unit potential (SMUP) size. MUNE is calculated by dividing the CMAP amplitude (peak-to-peak) by the SMUP amplitude (peak-to-peak). These electrophysiological techniques allow repeated measures in both neonatal and adult mice in such a manner that facilitates rapid analysis and data collection while reducing the number of animals required for experimental testing. Furthermore, these measures are similar to those recorded in human studies allowing more direct comparisons. PMID:26436455

  10. Time course of Ca and Ca-dependent K currents during molluscan nerve cell action potentials.

    PubMed

    Gola, M; Hussy, N; Crest, M; Ducreux, C

    1986-10-20

    The time courses of Ca and Ca-dependent K currents during Ca-dependent action potentials were obtained by recording the membrane currents produced in response to spike-like voltage clamp pulses before and after selective blockade of channels. The Ca current had a biphasic waveform with a first surge and a late, large entry. The Ca-dependent K(Ca) current onset was relatively fast with a peak occurring at half spike repolarization. The fast activation of the K(Ca) current was consecutive to the first Ca entry. It is concluded that K(Ca) currents constitute a powerful spike repolarization mechanism in addition to the voltage-dependent K currents. PMID:2430243

  11. Synapse-Level Determination of Action Potential Duration by K(+) Channel Clustering in Axons.

    PubMed

    Rowan, Matthew J M; DelCanto, Gina; Yu, Jianqing J; Kamasawa, Naomi; Christie, Jason M

    2016-07-20

    In axons, an action potential (AP) is thought to be broadcast as an unwavering binary pulse over its arbor, driving neurotransmission uniformly at release sites. Yet by recording from axons of cerebellar stellate cell (SC) interneurons, we show that AP width varies between presynaptic bouton sites, even within the same axon branch. The varicose geometry of SC boutons alone does not impose differences in spike duration. Rather, axonal patching revealed heterogeneous peak conductance densities of currents mediated mainly by fast-activating Kv3-type potassium channels, with clustered hotspots at boutons and restricted expression at adjoining shafts. Blockade of Kv channels at individual boutons indicates that currents immediately local to a release site direct spike repolarization at that location. Thus, the clustered arrangement and variable expression density of Kv3 channels at boutons are key determinants underlying compartmentalized control of AP width in a near synapse-by-synapse manner, multiplying the signaling capacity of these structures. PMID:27346528

  12. Effects of lead acetate on guinea pig - cochear microphonics, action potential, and motor nerve conduction velocity

    SciTech Connect

    Yamamura, K.; Maehara, N.; Terayama, K.; Ueno, N.; Kohyama, A.; Sawada, Y.; Kishi, R.

    1987-04-01

    Segmental demyelination and axonal degeneration of motor nerves induced by lead exposure is well known in man, and animals. The effect of lead acetate exposure to man may involve the cranial nerves, since vertigo and sensory neuronal deafness have been reported among lead workers. However, there are few reports concerning the dose-effects of lead acetate both to the peripheral nerve and the cranial VII nerve with measurement of blood lead concentration. The authors investigated the effects of lead acetate to the cochlea and the VIII nerve using CM (cochlear microphonics) and AP (action potential) of the guinea pigs. The effects of lead acetate to the sciatic nerve were measured by MCV of the sciatic nerve with measurement of blood lead concentration.

  13. 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. PMID:26561611

  14. Trichloroethanol alters action potentials in a subgroup of primary sensory neurones.

    PubMed

    Gruss, Marco; Hempelmann, Gunter; Scholz, Andreas

    2002-05-01

    We investigated the effects of 2,2,2-trichloroethanol (TCE), the active metabolite of chloral hydrate, on large-conductance calcium-activated K+ channels (BKCa channels) of dorsal root ganglion (DRG) neurones. In outside-out patches, 2 and 5 mM TCE increased the open probability of BKCa channels to 1.7-fold and 2.8-fold of control, respectively. In 50% of the cells investigated (group A) the action potential (AP) was shortened reversibly by TCE by 20% and the whole-cell outward-current was increased by 44%. Both effects could be antagonized by iberiotoxin. In a second group of neurone (group B), TCE prolonged the AP duration. The effects of TCE in group A, which was 20-fold more potent than ethanol on BKCa channels and AP might contribute to the described analgesic effect of chloral hydrate. PMID:11997700

  15. Control of action potential propagation by intracellular Ca2+ in cultured rat dorsal root ganglion cells.

    PubMed Central

    Lüscher, C; Lipp, P; Lüscher, H R; Niggli, E

    1996-01-01

    1. To assess the role of intracellular Ca2+ in action potential (AP) propagation, whole-cell recordings of cultured dorsal root ganglion (DRG) cells were carried out while Ca2+ was simultaneously measured with a laser-scanning confocal microscope. 2. Flash photolytic liberation of a Ca2+ buffer during trains of APs which partly failed to invade the DRG cell body immediately lowered intracellular Ca2+ and restored safe AP propagation. Furthermore, the speed of the propagated AP was reduced considerably when intracellular Ca2+ was increased by flash photolysis of caged Ca2+. 3. Both results suggest that intracellular Ca2+ regulates the safety factor for AP propagation and may thus provide a control mechanism for synaptic integration, which acts pre- as well as postsynaptically. Images Figure 1 Figure 3 PMID:8821131

  16. Effects of 4-aminopyridine on action potentials generation in mouse sinoauricular node strips

    PubMed Central

    Golovko, Vladimir; Gonotkov, Mikhail; Lebedeva, Elena

    2015-01-01

    The physiological role of Ito has yet to be clarified. The goal of this study is to investigate the possible contribution of the transient outward current (Ito) on the generation of transmembrane action potentials (APs) and the sensitivity of mouse sinoauricular node (SAN) cells to a 4-aminopyridine (4AP) as Ito blocker. The electrophysiological identification of cells was performed in the sinoauricular node artery area (nstrips = 38) of the subendocardial surface using microelectrode technique. In this study, for the first time, it was observed that dependence duration of action potential at the level of 20% repolarization (APD20) level under a 4AP concentration in the pacemaker SAN and auricular cells corresponds to a curve predicted by Hill’s equation. APD20 raised by 70% and spike duration of AP increased by 15–25%, when 4AP concentration was increased from 0.1 to 5.0 mmol/L. Auricular cells were found to be more sensitive to 4AP than true pacemaker cells. This was accompanied by a decrease in the upstroke velocity as compared to the control. Our data and previous findings in the literature lead us to hypothesize that the 4AP-sensitive current participates in the repolarization formation of pacemaker and auricular type cells. Thus, study concerning the inhibitory effects of lidocaine and TTX on APD20 can explain the phenomenon of the decrease in upstroke velocity, which, for the first time, was observed after exposure to 4AP. Duration of AP at the level of 20% repolarization (APD20) under a 4-AP concentration 0.5 mmol/L in the true pacemaker cells lengthen by 60–70% with a control. PMID:26156968

  17. Effects of 4-aminopyridine on action potentials generation in mouse sinoauricular node strips.

    PubMed

    Golovko, Vladimir; Gonotkov, Mikhail; Lebedeva, Elena

    2015-07-01

    The physiological role of Ito has yet to be clarified. The goal of this study is to investigate the possible contribution of the transient outward current (Ito) on the generation of transmembrane action potentials (APs) and the sensitivity of mouse sinoauricular node (SAN) cells to a 4-aminopyridine (4AP) as Ito blocker. The electrophysiological identification of cells was performed in the sinoauricular node artery area (nstrips = 38) of the subendocardial surface using microelectrode technique. In this study, for the first time, it was observed that dependence duration of action potential at the level of 20% repolarization (APD20) level under a 4AP concentration in the pacemaker SAN and auricular cells corresponds to a curve predicted by Hill's equation. APD20 raised by 70% and spike duration of AP increased by 15-25%, when 4AP concentration was increased from 0.1 to 5.0 mmol/L. Auricular cells were found to be more sensitive to 4AP than true pacemaker cells. This was accompanied by a decrease in the upstroke velocity as compared to the control. Our data and previous findings in the literature lead us to hypothesize that the 4AP-sensitive current participates in the repolarization formation of pacemaker and auricular type cells. Thus, study concerning the inhibitory effects of lidocaine and TTX on APD20 can explain the phenomenon of the decrease in upstroke velocity, which, for the first time, was observed after exposure to 4AP. Duration of AP at the level of 20% repolarization (APD20) under a 4-AP concentration 0.5 mmol/L in the true pacemaker cells lengthen by 60-70% with a control. PMID:26156968

  18. Mannan Oligosaccharides in Nursery Pig Nutrition and Their Potential Mode of Action

    PubMed Central

    Halas, Veronika; Nochta, Imre

    2012-01-01

    Simple Summary The aim of the paper is to provide a review of mannan oligosaccharide products in relation to their growth promoting effect and mode of action. Mannan oligosaccharide products maintain intestinal integrity and the digestive and absorptive function of the gut in the post-weaning period in pigs and enhance disease resistance by promoting antigen presentation. We find that dietary supplementation has growth promoting effects in pigs kept in a poor hygienic environment, while the positive effect of MOS is not observed in healthy pig herds with high hygienic standards. Abstract Mannan oligosaccharides (MOSs) are often referred to as one of the potential alternatives for antimicrobial growth promoters. The aim of the paper is to provide a review of mannan oligosaccharide products in relation to their growth promoting effect and mode of action based on the latest publications. We discuss the dietary impact of MOSs on (1) microbial changes, (2) morphological changes of gut tissue and digestibility of nutrients, and (3) immune response of pigs after weaning. Dietary MOSs maintain the intestinal integrity and the digestive and absorptive function of the gut in the post-weaning period. Recent results suggest that MOS enhances the disease resistance in swine by promoting antigen presentation facilitating thereby the shift from an innate to an adaptive immune response. Accordingly, dietary MOS supplementation has a potential growth promoting effect in pigs kept in a poor hygienic environment, while the positive effect of MOS is not observed in healthy pig herds with high hygienic standards that are able to maintain a high growth rate after weaning. PMID:26486920

  19. Glutamine and glutamate limit the shortening of action potential duration in anoxia-challenged rabbit hearts

    PubMed Central

    Drake, Kenneth J; Shotwell, Matthew S; Wikswo, John P; Sidorov, Veniamin Y

    2015-01-01

    In clinical conditions, amino acid supplementation is applied to improve contractile function, minimize ischemia/reperfusion injury, and facilitate postoperative recovery. It has been shown that glutamine enhances myocardial ATP/APD (action potential duration) and glutathione/oxidized glutathione ratios, and can increase hexosamine biosynthesis pathway flux, which is believed to play a role in cardioprotection. Here, we studied the effect of glutamine and glutamate on electrical activity in Langendorff-perfused rabbit hearts. The hearts were supplied by Tyrode's media with or without 2.5 mmol/L glutamine and 150 μmol/L glutamate, and exposed to two 6-min anoxias with 20-min recovery in between. Change in APD was detected using a monophasic action potential probe. A nonlinear mixed-effects regression technique was used to evaluate the effect of amino acids on APD over the experiment. Typically, the dynamic of APD change encompasses three phases: short transient increase (more prominent in the first episode), slow decrease, and fast increase (starting with the beginning of recovery). The effect of both anoxic challenge and glutamine/glutamate was cumulative, being more pronounced in the second anoxia. The amino acids' protective effect became largest by the end of anoxia – 20.0% (18.9, 95% CI: [2.6 ms, 35.1 ms]), during the first anoxia and 36.6% (27.1, 95% CI: [7.7 ms, 46.6 ms]), during the second. Following the second anoxia, APD difference between control and supplemented hearts progressively increased, attaining 10.8% (13.6, 95% CI: [4.1 ms, 23.1 ms]) at the experiments' end. Our data reveal APD stabilizing and suggest an antiarrhythmic capacity of amino acid supplementation in anoxic/ischemic conditions. PMID:26333831

  20. Learning about the Milky Way potential with generative stream models

    NASA Astrophysics Data System (ADS)

    McMillan, Paul

    2015-08-01

    Streams are formed when satellites of a galaxy are pulled apart by tidal forces and the stars then drift apart because they are placed on different orbits. Therefore it is the difference between the orbits that determines the shape of the stream (rather than the stream nearly following a single orbit). This means that a good model of the structure of a stream can be defined in terms of orbital frequencies and angle coordinates.I’ll talk about a new method for creating generative models of streams based on this insight. Given that the orbital frequencies are directly related to the actions, the method of torus modelling (which finds the orbits corresponding to a given value of actions) is ideally suited to the problem. I’ll show results from a new method that interpolates between orbits (tori), to rapidly generate stream models that can be used to determine the gravitational potential that the stream is moving in. This method has now been made publicly available.

  1. Hydramacin-1 in Action: Scrutinizing the Barnacle Model

    PubMed Central

    Michalek, Matthias; Vincent, Bruno; Podschun, Rainer; Grötzinger, Joachim; Bechinger, Burkhard

    2013-01-01

    Hydramacin-1 (HM1) from the metazoan Hydra exerts antimicrobial activity against a wide range of bacterial strains. Notably, HM1 induces the aggregation of bacterial cells, accompanied by precipitation. To date, the proposed mechanism of peptide-lipid interaction, termed the barnacle model, has not been described on the molecular level. Here, we show by biochemical and biophysical techniques that the lipid-peptide interactions of HM1 are initiated by electrostatic and hydrophobic effects, in particular, by tryptophan and neighboring polar amino acid residues that cause an interfacial localization of the peptide between two self-contained lipid bilayers. The high binding constants of HM1 upon lipid interaction are in the range of other potent antimicrobial peptides, e.g., magainin, and can be reasonably explained by two distinct epitopes on the surface of the peptide's global structure, which both contain SWT(K/R) motifs. The residues of this motif favor localization of the peptide in the head group region of phospholipid bilayers up to a penetration depth of 4 Å and a minor participation of the lipids' hydrocarbon regions. Our results expand the knowledge about the molecular modes of action antimicrobial peptides use to tackle their target cells. Furthermore, the aggregation of living bacteria by HM1 was observed for a broad range of Gram-positive and Gram-negative bacteria. Therefore, the detailed view of peptide-lipid interactions described by the barnacle model consolidates it among the established models. PMID:23587944

  2. 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

  3. Simple intramolecular model potentials for water

    SciTech Connect

    Dang, L.X.; Pettitt, B.M.

    1987-06-04

    An effective intramolecular potential is presented for use in conjunction with existing three-site models of water. Two commonly used internal geometries were fit to the same form yielding slightly different parametrizations. By including a Urey-Bradley-like term in an otherwise standard molecular mechanics form it was found that the experimental transition frequencies of water monomer can be reproduced accurately. Good qualitative agreements for spectral shifts were subsequently found for the models in condensed-phase applications. Harmonic analysis of clusters indicates good qualitative agreement with experimental environmental shifts in frequencies at low temperatures for these models. This model should be useful for a wide variety of applications including simulations of biopolymers and ionic solutions.

  4. Novel description of ionic currents recorded with the action potential clamp technique: application to excitatory currents in suprachiasmatic nucleus neurons

    PubMed Central

    2015-01-01

    The traditional method of recording ionic currents in neurons has been with voltage-clamp steps. Other waveforms such as action potentials (APs) can be used. The AP clamp method reveals contributions of ionic currents that underlie excitability during an AP (Bean BP. Nat Rev Neurosci 8: 451–465, 2007). A novel usage of the method is described in this report. An experimental recording of an AP from the literature is digitized and applied computationally to models of ionic currents. These results are compared with experimental AP-clamp recordings for model verification or, if need be, alterations to the model. The method is applied to the tetrodotoxin-sensitive sodium ion current, INa, and the calcium ion current, ICa, from suprachiasmatic nucleus (SCN) neurons (Jackson AC, Yao GL, Bean BP. J Neurosci 24: 7985–7998, 2004). The latter group reported voltage-step and AP-clamp results for both components. A model of INa is constructed from their voltage-step results. The AP clamp computational methodology applied to that model compares favorably with experiment, other than a modest discrepancy close to the peak of the AP that has not yet been resolved. A model of ICa was constructed from both voltage-step and AP-clamp results of this component. The model employs the Goldman-Hodgkin-Katz equation for the current-voltage relation rather than the traditional linear dependence of this aspect of the model on the Ca2+ driving force. The long-term goal of this work is a mathematical model of the SCN AP. The method is general. It can be applied to any excitable cell. PMID:26041831

  5. Simultaneous Optical Mapping of Intracellular Free Calcium and Action Potentials from Langendorff Perfused Hearts

    PubMed Central

    Salama, Guy; Hwang, Seong-min

    2015-01-01

    The cardiac action potential (AP) controls the rise and fall of intracellular free Ca2+ (Cai), and thus the amplitude and kinetics of force generation. Besides excitation-contraction coupling, the reverse process where Cai influences the AP through Cai-dependent ionic currents has been implicated as the mechanism underlying QT alternans and cardiac arrhythmias in heart failure, ischemia/reperfusion, cardiac myopathy, myocardial infarction, congenital and drug-induced long QT syndrome, and ventricular fibrillation. The development of dual optical mapping at high spatial and temporal resolution provides a powerful tool to investigate the role of Cai anomalies in eliciting cardiac arrhythmias. This unit describes experimental protocols to map APs and Cai transients from perfused hearts by labeling the heart with two fluorescent dyes, one to measure transmembrane potential (Vm), the other Cai transients. High spatial and temporal resolution is achieved by selecting Vm and Cai probes with the same excitation but different emission wavelengths, to avoid cross-talk and mechanical components. PMID:19575468

  6. 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.

  7. Electrical Identification and Selective Microstimulation of Neuronal Compartments Based on Features of Extracellular Action Potentials.

    PubMed

    Radivojevic, Milos; Jäckel, David; Altermatt, Michael; Müller, Jan; Viswam, Vijay; Hierlemann, Andreas; Bakkum, Douglas J

    2016-01-01

    A detailed, high-spatiotemporal-resolution characterization of neuronal responses to local electrical fields and the capability of precise extracellular microstimulation of selected neurons are pivotal for studying and manipulating neuronal activity and circuits in networks and for developing neural prosthetics. Here, we studied cultured neocortical neurons by using high-density microelectrode arrays and optical imaging, complemented by the patch-clamp technique, and with the aim to correlate morphological and electrical features of neuronal compartments with their responsiveness to extracellular stimulation. We developed strategies to electrically identify any neuron in the network, while subcellular spatial resolution recording of extracellular action potential (AP) traces enabled their assignment to the axon initial segment (AIS), axonal arbor and proximal somatodendritic compartments. Stimulation at the AIS required low voltages and provided immediate, selective and reliable neuronal activation, whereas stimulation at the soma required high voltages and produced delayed and unreliable responses. Subthreshold stimulation at the soma depolarized the somatic membrane potential without eliciting APs. PMID:27510732

  8. Variability of Action Potentials Within and Among Cardiac Cell Clusters Derived from Human Embryonic Stem Cells.

    PubMed

    Zhu, Renjun; Millrod, Michal A; Zambidis, Elias T; Tung, Leslie

    2016-01-01

    Electrophysiological variability in cardiomyocytes derived from pluripotent stem cells continues to be an impediment for their scientific and translational applications. We studied the variability of action potentials (APs) recorded from clusters of human embryonic stem cell-derived cardiomyocytes (hESC-CMs) using high-resolution optical mapping. Over 23,000 APs were analyzed through four parameters: APD30, APD80, triangulation and fractional repolarization. Although measures were taken to reduce variability due to cell culture conditions and rate-dependency of APs, we still observed significant variability in APs among and within the clusters. However, similar APs were found in spatial locations with close proximity, and in some clusters formed distinct regions having different AP characteristics that were reflected as separate peaks in the AP parameter distributions, suggesting multiple electrophysiological phenotypes. Using a recently developed automated method to group cells based on their entire AP shape, we identified distinct regions of different phenotypes within single clusters and common phenotypes across different clusters when separating APs into 2 or 3 subpopulations. The systematic analysis of the heterogeneity and potential phenotypes of large populations of hESC-CMs can be used to evaluate strategies to improve the quality of pluripotent stem cell-derived cardiomyocytes for use in diagnostic and therapeutic applications and in drug screening. PMID:26729331

  9. Electrical Identification and Selective Microstimulation of Neuronal Compartments Based on Features of Extracellular Action Potentials

    PubMed Central

    Radivojevic, Milos; Jäckel, David; Altermatt, Michael; Müller, Jan; Viswam, Vijay; Hierlemann, Andreas; Bakkum, Douglas J.

    2016-01-01

    A detailed, high-spatiotemporal-resolution characterization of neuronal responses to local electrical fields and the capability of precise extracellular microstimulation of selected neurons are pivotal for studying and manipulating neuronal activity and circuits in networks and for developing neural prosthetics. Here, we studied cultured neocortical neurons by using high-density microelectrode arrays and optical imaging, complemented by the patch-clamp technique, and with the aim to correlate morphological and electrical features of neuronal compartments with their responsiveness to extracellular stimulation. We developed strategies to electrically identify any neuron in the network, while subcellular spatial resolution recording of extracellular action potential (AP) traces enabled their assignment to the axon initial segment (AIS), axonal arbor and proximal somatodendritic compartments. Stimulation at the AIS required low voltages and provided immediate, selective and reliable neuronal activation, whereas stimulation at the soma required high voltages and produced delayed and unreliable responses. Subthreshold stimulation at the soma depolarized the somatic membrane potential without eliciting APs. PMID:27510732

  10. Spatial dynamics of action potentials estimated by dendritic Ca(2+) signals in insect projection neurons.

    PubMed

    Ogawa, Hiroto; Mitani, Ruriko

    2015-11-13

    The spatial dynamics of action potentials, including their propagation and the location of spike initiation zone (SIZ), are crucial for the computation of a single neuron. Compared with mammalian central neurons, the spike dynamics of invertebrate neurons remain relatively unknown. Thus, we examined the spike dynamics based on single spike-induced Ca(2+) signals in the dendrites of cricket mechanosensory projection neurons, known as giant interneurons (GIs). The Ca(2+) transients induced by a synaptically evoked single spike were larger than those induced by an antidromic spike, whereas subthreshold synaptic potentials caused no elevation of Ca(2+). These results indicate that synaptic activity enhances the dendritic Ca(2+) influx through voltage-gated Ca(2+) channels. Stimulation of the presynaptic sensory afferents ipsilateral to the recording site evoked a dendritic spike with higher amplitude than contralateral stimulation, thereby suggesting that alteration of the spike waveform resulted in synaptic enhancement of the dendritic Ca(2+) transients. The SIZ estimated from the spatial distribution of the difference in the Ca(2+) amplitude was distributed throughout the right and left dendritic branches across the primary neurite connecting them in GIs. PMID:26456645

  11. Generalized iterative annealing model for the action of RNA chaperones

    NASA Astrophysics Data System (ADS)

    Hyeon, Changbong; Thirumalai, D.

    2013-09-01

    As a consequence of the rugged landscape of RNA molecules their folding is described by the kinetic partitioning mechanism according to which only a small fraction (ϕF) reaches the folded state while the remaining fraction of molecules is kinetically trapped in misfolded intermediates. The transition from the misfolded states to the native state can far exceed biologically relevant time. Thus, RNA folding in vivo is often aided by protein cofactors, called RNA chaperones, that can rescue RNAs from a multitude of misfolded structures. We consider two models, based on chemical kinetics and chemical master equation, for describing assisted folding. In the passive model, applicable for class I substrates, transient interactions of misfolded structures with RNA chaperones alone are sufficient to destabilize the misfolded structures, thus entropically lowering the barrier to folding. For this mechanism to be efficient the intermediate ribonucleoprotein complex between collapsed RNA and protein cofactor should have optimal stability. We also introduce an active model (suitable for stringent substrates with small ϕF), which accounts for the recent experimental findings on the action of CYT-19 on the group I intron ribozyme, showing that RNA chaperones do not discriminate between the misfolded and the native states. In the active model, the RNA chaperone system utilizes chemical energy of adenosine triphosphate hydrolysis to repeatedly bind and release misfolded and folded RNAs, resulting in substantial increase of yield of the native state. The theory outlined here shows, in accord with experiments, that in the steady state the native state does not form with unit probability.

  12. Models, Definitions, and Outcome Variables of Action Learning: A Synthesis with Implications for HRD

    ERIC Educational Resources Information Center

    Chenhall, Everon C.; Chermack, Thomas J.

    2010-01-01

    Purpose: The purpose of this paper is to propose an integrated model of action learning based on an examination of four reviewed action learning models, definitions, and espoused outcomes. Design/methodology/approach: A clear articulation of the strengths and limitations of each model was essential to developing an integrated model, which could be…

  13. Potential involvement of serotonergic signaling in ketamine's antidepressant actions: A critical review.

    PubMed

    du Jardin, Kristian Gaarn; Müller, Heidi Kaastrup; Elfving, Betina; Dale, Elena; Wegener, Gregers; Sanchez, Connie

    2016-11-01

    A single i.v. infusion of ketamine, classified as an N-methyl-d-aspartate (NMDA) receptor antagonist, may alleviate depressive symptoms within hours of administration in treatment resistant depressed patients, and the antidepressant effect may last for several weeks. These unique therapeutic properties have prompted researchers to explore the mechanisms mediating the antidepressant effects of ketamine, but despite many efforts, no consensus on its antidepressant mechanism of action has been reached. Recent preclinical reports have associated the neurotransmitter serotonin (5-hydroxytryptamine; 5-HT) with the antidepressant-like action of ketamine. Here, we review the current evidence for a serotonergic role in ketamine's antidepressant effects. The pharmacological profile of ketamine may include equipotent activity on several non-NMDA targets, and the current hypotheses for the mechanisms responsible for ketamine's antidepressant activity do not appear to preclude the possibility that non-glutamate neurotransmitters are involved in the antidepressant effects. At multiple levels, the serotonergic and glutamatergic systems interact, and such crosstalk could support the notion that changes in serotonergic neurotransmission may impact ketamine's antidepressant potential. In line with these prospects, ketamine may increase 5-HT levels in the prefrontal cortex of rats, plausibly via hippocampal NMDA receptor inhibition and activation of α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors. In addition, a number of preclinical studies suggest that the antidepressant-like effects of ketamine may depend on endogenous activation of 5-HT receptors. Recent imaging and behavioral data predominantly support a role for 5-HT1A or 5-HT1B receptors, but the full range of 5-HT receptors has currently not been systematically investigated in this context. Furthermore, the nature of any 5-HT dependent mechanism in ketamine's antidepressant effect is currently not

  14. Theoretical study of L-type Ca(2+) current inactivation kinetics during action potential repolarization and early afterdepolarizations.

    PubMed

    Morotti, Stefano; Grandi, Eleonora; Summa, Aurora; Ginsburg, Kenneth S; Bers, Donald M

    2012-09-15

    Sarcoplasmic reticulum (SR) Ca(2+) release mediates excitation–contraction coupling (ECC) in cardiac myocytes. It is triggered upon membrane depolarization by entry of Ca(2+) via L-type Ca(2+) channels (LTCCs), which undergo both voltage- and Ca(2+)-dependent inactivation (VDI and CDI, respectively). We developed improved models of L-type Ca(2+) current and SR Ca(2+) release within the framework of the Shannon-Bers rabbit ventricular action potential (AP) model. The formulation of SR Ca(2+) release was modified to reproduce high ECC gain at negative membrane voltages. An existing LTCC model was extended to reflect more faithfully contributions of CDI and VDI to total inactivation. Ba(2+) current inactivation included an ion-dependent component (albeit small compared with CDI), in addition to pure VDI. Under physiological conditions (during an AP) LTCC inactivates predominantly via CDI, which is controlled mostly by SR Ca(2+) release during the initial AP phase, but by Ca(2+) through LTCCs for the remaining part. Simulations of decreased CDI or K(+) channel block predicted the occurrence of early and delayed after depolarizations. Our model accurately describes ECC and allows dissection of the relative contributions of different Ca(2+) sources to total CDI, and the relative roles of CDI and VDI, during normal and abnormal repolarization. PMID:22586219

  15. Cytoplasmic Ca2+, K+, Cl-, and NO3- Activities in the Liverwort Conocephalum conicum L. at Rest and during Action Potentials.

    PubMed Central

    Trebacz, K.; Simonis, W.; Schonknecht, G.

    1994-01-01

    Intracellular Ca2+, K+, Cl-, and NO3- activities were measured with ion-selective microelectrodes in the liverwort Conocephalum conicum L. at rest, during dark/light changes, and in the course of action potentials triggered by light or electrical stimuli. The average free cytosolic Ca2+ concentration was 231 [plus or minus] 65 nM. We did not observe any light-dependent changes of the free cytosolic Ca2+ concentration as long as no action potential was triggered. During action potentials, on average a 2-fold increase of the free cytoplasmic Ca2+ concentration was recorded. Intracellular K+ activity was 76 [plus or minus] 10 mM. It did not depend on K+ concentration changes in the bath solution between 0.1 and 10 mM. The average equilibrium potential for K+ in the standard medium containing 1 mM K+ was -110 mV, which differed significantly from the resting potential of -151 [plus or minus] 2 mV. During action potentials, either a slight decrease or no changes in intracellular K+ activity were recorded. The average Cl- activity was 7.4 [plus or minus] 0.2 mM in the cytoplasm and 43.5 [plus or minus] 7 mM in the vacuole. The activities of NO3- were 0.63 [plus or minus] 0.05 mM in the cytoplasm and 3.0 [plus or minus] 0.3 mM in the vacuole. For both anions the vacuolar activity was 5 to 6 times higher than the cytoplasmic activity. After the light was switched off both the Cl- and the NO3- activity showed either no change or a slight increase. Illumination caused a gradual return to previous values or no change. During action potentials a slight decrease of intracellular Cl- activity was recorded. It was concluded that in Conocephalum, as in characean cells, chloride channels are involved in the depolarization phase of the action potentials. We discuss a model for the ion fluxes during an action potential in Conocephalum. PMID:12232388

  16. Averaging methods for extracting representative waveforms from motor unit action potential trains.

    PubMed

    Malanda, Armando; Navallas, Javier; Rodriguez-Falces, Javier; Rodriguez-Carreño, Ignacio; Gila, Luis

    2015-08-01

    In the context of quantitative electromyography (EMG), it is of major interest to obtain a waveform that faithfully represents the set of potentials that constitute a motor unit action potential (MUAP) train. From this waveform, various parameters can be determined in order to characterize the MUAP for diagnostic analysis. The aim of this work was to conduct a thorough, in-depth review, evaluation and comparison of state-of-the-art methods for composing waveforms representative of MUAP trains. We evaluated nine averaging methods: Ensemble (EA), Median (MA), Weighted (WA), Five-closest (FCA), MultiMUP (MMA), Split-sweep median (SSMA), Sorted (SA), Trimmed (TA) and Robust (RA) in terms of three general-purpose signal processing figures of merit (SPMF) and seven clinically-used MUAP waveform parameters (MWP). The convergence rate of the methods was assessed as the number of potentials per MUAP train (NPM) required to reach a level of performance that was not significantly improved by increasing this number. Test material comprised 78 MUAP trains obtained from the tibialis anterioris of seven healthy subjects. Error measurements related to all SPMF and MWP parameters except MUAP amplitude descended asymptotically with increasing NPM for all methods. MUAP amplitude showed a consistent bias (around 4% for EA and SA and 1-2% for the rest). MA, TA and SSMA had the lowest SPMF and MWP error figures. Therefore, these methods most accurately preserve and represent MUAP physiological information of utility in clinical medical practice. The other methods, particularly WA, performed noticeably worse. Convergence rate was similar for all methods, with NPM values averaged among the nine methods, which ranged from 10 to 40, depending on the waveform parameter evaluated. PMID:25962870

  17. The Reflective Teacher Leader: An Action Research Model

    ERIC Educational Resources Information Center

    Furtado, Leena; Anderson, Dawnette

    2012-01-01

    This study presents four teacher reflections from action research projects ranging from kindergarten to adult school improvements. A teacher leadership matrix guided participants to connect teaching and learning theory to best practices by exploring uncharted territory within an iterative cycle of research and action. Teachers developed the…

  18. Effect of mental challenge induced by movie clips on action potential duration in normal human subjects independent of heart rate

    PubMed Central

    Child, Nicholas; Hanson, Ben; Bishop, Martin; Rinaldi, Christopher A; Bostock, Julian; Western, David; Cooklin, Michael; O’Neil, Mark; Wright, Matthew; Razavi, Reza; Gill, Jaswinder; Taggart, Peter

    2014-01-01

    Background Mental stress and emotion have long been associated with ventricular arrhythmias and sudden death in animal models and humans. The effect of mental challenge on ventricular action potential duration (APD) in conscious healthy humans has not been reported. Methods and Results Activation recovery intervals (ARI) measured from unipolar electrograms as a surrogate for APD (n=19) were recorded from right and left ventricular endocardium during steady state pacing while subjects watched an emotionally charged film clip. To assess the possible modulating role of altered respiration on APD, the subjects then repeated the same breathing pattern they had during the stress, but without the movie clip. Haemodynamic parameters (mean, systolic, and diastolic blood pressure, and rate of pressure increase) and respiration rate increased during the stressful part of the film clip (p=0.001). APD decreased during the stressful parts of the film clip, eg for global RV ARI at end of film clip 193.8ms (SD 14) vs 198.0ms (SD13) during the matched breathing control (end film LV 199.8ms (SD16) vs control 201.6ms (SD15), p=0.004. Respiration rate increased during the stressful part of the film clip (by 2 breaths/minute), and was well matched in the respective control period without any haemodynamic or ARI changes. Conclusions Our results document for the first time direct recordings of the effect of a mental challenge protocol on ventricular action potential duration in conscious humans. The effect of mental challenge on APD was not secondary to emotionally-induced altered respiration or heart rate. PMID:24833641

  19. Matching universal behavior with potential models

    NASA Astrophysics Data System (ADS)

    Álvarez-Rodríguez, R.; Deltuva, A.; Gattobigio, M.; Kievsky, A.

    2016-06-01

    Two-, three-, and four-boson systems are studied close to the unitary limit using potential models constructed to reproduce the minimal information given by the two-body scattering length a and the two-body binding energy or virtual-state energy E2. The particular path used to reach the unitary limit is given by varying the potential strength. In this way the energy spectrum in the three- and four-boson systems is computed. The lowest-energy states show finite-range effects absorbed in the construction of level functions that can be used to study real systems. Higher-energy levels are free from finite-range effects, therefore the corresponding level functions tend to the zero-range universal function. Using this property, a zero-range equation for the four-boson system is proposed and the four-boson universal function is computed.

  20. Bursting regimes in a reaction-diffusion system with action potential-dependent equilibrium.

    PubMed

    Meier, Stephen R; Lancaster, Jarrett L; Starobin, Joseph M

    2015-01-01

    The equilibrium Nernst potential plays a critical role in neural cell dynamics. A common approximation used in studying electrical dynamics of excitable cells is that the ionic concentrations inside and outside the cell membranes act as charge reservoirs and remain effectively constant during excitation events. Research into brain electrical activity suggests that relaxing this assumption may provide a better understanding of normal and pathophysiological functioning of the brain. In this paper we explore time-dependent ionic concentrations by allowing the ion-specific Nernst potentials to vary with developing transmembrane potential. As a specific implementation, we incorporate the potential-dependent Nernst shift into a one-dimensional Morris-Lecar reaction-diffusion model. Our main findings result from a region in parameter space where self-sustaining oscillations occur without external forcing. Studying the system close to the bifurcation boundary, we explore the vulnerability of the system with respect to external stimulations which disrupt these oscillations and send the system to a stable equilibrium. We also present results for an extended, one-dimensional cable of excitable tissue tuned to this parameter regime and stimulated, giving rise to complex spatiotemporal pattern formation. Potential applications to the emergence of neuronal bursting in similar two-variable systems and to pathophysiological seizure-like activity are discussed. PMID:25823018

  1. Bursting Regimes in a Reaction-Diffusion System with Action Potential-Dependent Equilibrium

    PubMed Central

    Meier, Stephen R.; Lancaster, Jarrett L.; Starobin, Joseph M.

    2015-01-01

    The equilibrium Nernst potential plays a critical role in neural cell dynamics. A common approximation used in studying electrical dynamics of excitable cells is that the ionic concentrations inside and outside the cell membranes act as charge reservoirs and remain effectively constant during excitation events. Research into brain electrical activity suggests that relaxing this assumption may provide a better understanding of normal and pathophysiological functioning of the brain. In this paper we explore time-dependent ionic concentrations by allowing the ion-specific Nernst potentials to vary with developing transmembrane potential. As a specific implementation, we incorporate the potential-dependent Nernst shift into a one-dimensional Morris-Lecar reaction-diffusion model. Our main findings result from a region in parameter space where self-sustaining oscillations occur without external forcing. Studying the system close to the bifurcation boundary, we explore the vulnerability of the system with respect to external stimulations which disrupt these oscillations and send the system to a stable equilibrium. We also present results for an extended, one-dimensional cable of excitable tissue tuned to this parameter regime and stimulated, giving rise to complex spatiotemporal pattern formation. Potential applications to the emergence of neuronal bursting in similar two-variable systems and to pathophysiological seizure-like activity are discussed. PMID:25823018

  2. 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

  3. Role of the calcium-independent transient outward current I(to1) in shaping action potential morphology and duration.

    PubMed

    Greenstein, J L; Wu, R; Po, S; Tomaselli, G F; Winslow, R L

    2000-11-24

    The Kv4.3-encoded current (I:(Kv4.3)) has been identified as the major component of the voltage-dependent Ca(2+)-independent transient outward current (I:(to1)) in human and canine ventricular cells. Experimental evidence supports a correlation between I:(to1) density and prominence of the phase 1 notch; however, the role of I:(to1) in modulating action potential duration (APD) remains unclear. To help resolve this role, Markov state models of the human and canine Kv4.3- and Kv1.4-encoded currents at 35 degrees C are developed on the basis of experimental measurements. A model of canine I:(to1) is formulated as the combination of these Kv4.3 and Kv1.4 currents and is incorporated into an existing canine ventricular myocyte model. Simulations demonstrate strong coupling between L-type Ca(2+) current and I:(Kv4.3) and predict a bimodal relationship between I:(Kv4.3) density and APD whereby perturbations in I:(Kv4.3) density may produce either prolongation or shortening of APD, depending on baseline I:(to1) current level. PMID:11090548

  4. Antifungal potential of Sideroxylon obtusifolium and Syzygium cumini and their mode of action against Candida albicans.

    PubMed

    Pereira, Jozinete Vieira; Freires, Irlan Almeida; Castilho, Aline Rogéria; da Cunha, Marcos Guilherme; Alves, Harley da Silva; Rosalen, Pedro Luiz

    2016-10-01

    Context The emergence of resistant pathogens and toxicity of antifungals have encouraged an active search for novel candidates to manage Candida biofilms. Objective In this study, the little known species Sideroxylon obtusifolium T.D. Penn (Sapotacea) and Syzygium cumini (L.) Skeels (Myrtaceae), from the Caatinga biome in Brazil were chemically characterized and explored for their antifungal potential against C. albicans. Materials and methods We determined the effects of hydroalcoholic extracts/fractions upon fungal growth (minimum inhibitory and fungicidal concentrations, MIC/MFC), biofilm morphology (scanning electron microscopy) and viability (confocal laser scanning microscopy), proposed their mode of action (sorbitol and ergosterol assays), and finally investigated their effects against macrophage and keratinocyte cells in a cell-based assay. Data were analysed using one-way analysis of variance with Tukey-Kramer post-test (α = 0.05). Results The n-butanol (Nb) fraction from S. obtusifolium and S. cumini extract (Sc) showed flavonoids (39.11 ± 6.62 mg/g) and saponins (820.35 ± 225.38 mg/g), respectively, in their chemical composition and demonstrated antifungal activity, with MICs of 62.5 and 125 μg/mL, respectively. Nb and Sc may complex with ergosterol as there was a 4-16-fold increase in MICs in the presence of exogenous ergosterol, leading to disrupted permeability of cell membrane. Deleterious effects were observed on morphology and viability of treated biofilms from concentrations as low as their MICs and higher. Sc was not toxic to macrophages and keratinocytes at these concentrations (p > 0.05), unlike Nb. Conclusions Nb and Sc demonstrated considerable antifungal activity and should be further investigated as potential alternative candidates to treat Candida biofilms. PMID:26987037

  5. The Venus Flytrap Dionaea muscipula Counts Prey-Induced Action Potentials to Induce Sodium Uptake.

    PubMed

    Böhm, Jennifer; Scherzer, Sönke; Krol, Elzbieta; Kreuzer, Ines; von Meyer, Katharina; Lorey, Christian; Mueller, Thomas D; Shabala, Lana; Monte, Isabel; Solano, Roberto; Al-Rasheid, Khaled A S; Rennenberg, Heinz; Shabala, Sergey; Neher, Erwin; Hedrich, Rainer

    2016-02-01

    Carnivorous plants, such as the Venus flytrap (Dionaea muscipula), depend on an animal diet when grown in nutrient-poor soils. When an insect visits the trap and tilts the mechanosensors on the inner surface, action potentials (APs) are fired. After a moving object elicits two APs, the trap snaps shut, encaging the victim. Panicking preys repeatedly touch the trigger hairs over the subsequent hours, leading to a hermetically closed trap, which via the gland-based endocrine system is flooded by a prey-decomposing acidic enzyme cocktail. Here, we asked the question as to how many times trigger hairs have to be stimulated (e.g., now many APs are required) for the flytrap to recognize an encaged object as potential food, thus making it worthwhile activating the glands. By applying a series of trigger-hair stimulations, we found that the touch hormone jasmonic acid (JA) signaling pathway is activated after the second stimulus, while more than three APs are required to trigger an expression of genes encoding prey-degrading hydrolases, and that this expression is proportional to the number of mechanical stimulations. A decomposing animal contains a sodium load, and we have found that these sodium ions enter the capture organ via glands. We identified a flytrap sodium channel DmHKT1 as responsible for this sodium acquisition, with the number of transcripts expressed being dependent on the number of mechano-electric stimulations. Hence, the number of APs a victim triggers while trying to break out of the trap identifies the moving prey as a struggling Na(+)-rich animal and nutrition for the plant. PMID:26804557

  6. The Venus Flytrap Dionaea muscipula Counts Prey-Induced Action Potentials to Induce Sodium Uptake

    PubMed Central

    Böhm, Jennifer; Scherzer, Sönke; Krol, Elzbieta; Kreuzer, Ines; von Meyer, Katharina; Lorey, Christian; Mueller, Thomas D.; Shabala, Lana; Monte, Isabel; Solano, Roberto; Al-Rasheid, Khaled A.S.; Rennenberg, Heinz; Shabala, Sergey; Neher, Erwin; Hedrich, Rainer

    2016-01-01

    Summary Carnivorous plants, such as the Venus flytrap (Dionaea muscipula), depend on an animal diet when grown in nutrient-poor soils. When an insect visits the trap and tilts the mechanosensors on the inner surface, action potentials (APs) are fired. After a moving object elicits two APs, the trap snaps shut, encaging the victim. Panicking preys repeatedly touch the trigger hairs over the subsequent hours, leading to a hermetically closed trap, which via the gland-based endocrine system is flooded by a prey-decomposing acidic enzyme cocktail. Here, we asked the question as to how many times trigger hairs have to be stimulated (e.g., now many APs are required) for the flytrap to recognize an encaged object as potential food, thus making it worthwhile activating the glands. By applying a series of trigger-hair stimulations, we found that the touch hormone jasmonic acid (JA) signaling pathway is activated after the second stimulus, while more than three APs are required to trigger an expression of genes encoding prey-degrading hydrolases, and that this expression is proportional to the number of mechanical stimulations. A decomposing animal contains a sodium load, and we have found that these sodium ions enter the capture organ via glands. We identified a flytrap sodium channel DmHKT1 as responsible for this sodium acquisition, with the number of transcripts expressed being dependent on the number of mechano-electric stimulations. Hence, the number of APs a victim triggers while trying to break out of the trap identifies the moving prey as a struggling Na+-rich animal and nutrition for the plant. Video Abstract PMID:26804557

  7. Action potential amplitude as a noninvasive indicator of motor unit-specific hypertrophy.

    PubMed

    Pope, Zachary K; Hester, Garrett M; Benik, Franklin M; DeFreitas, Jason M

    2016-05-01

    Skeletal muscle fibers hypertrophy in response to strength training, with type II fibers generally demonstrating the greatest plasticity in regards to cross-sectional area (CSA). However, assessing fiber type-specific CSA in humans requires invasive muscle biopsies. With advancements in the decomposition of surface electromyographic (sEMG) signals recorded using multichannel electrode arrays, the firing properties of individual motor units (MUs) can now be detected noninvasively. Since action potential amplitude (APSIZE) has a documented relationship with muscle fiber size, as well as with its parent MU's recruitment threshold (RT) force, our purpose was to examine if MU APSIZE, as a function of its RT (i.e., the size principle), could potentially be used as a longitudinal indicator of MU-specific hypertrophy. By decomposing the sEMG signals from the vastus lateralis muscle of 10 subjects during maximal voluntary knee extensions, we noninvasively assessed the relationship between MU APSIZE and RT before and immediately after an 8-wk strength training intervention. In addition to significant increases in muscle size and strength (P < 0.02), our data show that training elicited an increase in MU APSIZE of high-threshold MUs. Additionally, a large portion of the variance (83.6%) in the change in each individual's relationship between MU APSIZE and RT was explained by training-induced changes in whole muscle CSA (obtained via ultrasonography). Our findings suggest that the noninvasive, electrophysiological assessment of longitudinal changes to MU APSIZE appears to reflect hypertrophy specific to MUs across the RT continuum. PMID:26936975

  8. Wavelet Transform for Real-Time Detection of Action Potentials in Neural Signals

    PubMed Central

    Quotb, Adam; Bornat, Yannick; Renaud, Sylvie

    2011-01-01

    We present a study on wavelet detection methods of neuronal action potentials (APs). Our final goal is to implement the selected algorithms on custom integrated electronics for on-line processing of neural signals; therefore we take real-time computing as a hard specification and silicon area as a price to pay. Using simulated neural signals including APs, we characterize an efficient wavelet method for AP extraction by evaluating its detection rate and its implementation cost. We compare software implementation for three methods: adaptive threshold, discrete wavelet transform (DWT), and stationary wavelet transform (SWT). We evaluate detection rate and implementation cost for detection functions dynamically comparing a signal with an adaptive threshold proportional to its SD, where the signal is the raw neural signal, respectively: (i) non-processed; (ii) processed by a DWT; (iii) processed by a SWT. We also use different mother wavelets and test different data formats to set an optimal compromise between accuracy and silicon cost. Detection accuracy is evaluated together with false negative and false positive detections. Simulation results show that for on-line AP detection implemented on a configurable digital integrated circuit, APs underneath the noise level can be detected using SWT with a well-selected mother wavelet, combined to an adaptive threshold. PMID:21811455

  9. Dopaminergic modulation of axonal potassium channels and action potential waveform in pyramidal neurons of prefrontal cortex.

    PubMed

    Yang, Jing; Ye, Mingyu; Tian, Cuiping; Yang, Mingpo; Wang, Yonghong; Shu, Yousheng

    2013-07-01

    Voltage-gated K(+) (KV) channels play critical roles in shaping neuronal signals. KV channels distributed in the perisomatic regions and thick dendrites of cortical pyramidal neurons have been extensively studied. However, the properties and regulation of KV channels distributed in the thin axons remain unknown. In this study, by performing somatic and axonal patch-clamp recordings from layer 5 pyramidal neurons of prefrontal cortical slices, we showed that the rapidly inactivating A-currents mediated the transient K(+) currents evoked by action potential (AP) waveform command (KAP) at the soma, whereas the rapidly activating but slowly inactivating KV1-mediated D-currents dominated the KAP at the axon. In addition, activation of D1-like receptors for dopamine decreased the axonal K(+) currents, as a result of an increase in the activity of cAMP-PKA pathway. In contrast, activation of D2-like receptors showed an opposite effect on the axonal K(+) currents. Further experiments demonstrated that functional D1-like receptors were expressed at the main axon trunk and their activation could broaden the waveforms of axonal APs. Together, these results show that axonal KV channels were subjected to dopamine modulation, and this modulation could regulate the waveforms of propagating APs at the axon, suggesting an important role of dopaminergic modulation of axonal KV channels in regulating neuronal signalling. PMID:23568892

  10. Skeletal muscle atrophy: Potential therapeutic agents and their mechanisms of action.

    PubMed

    Dutt, Vikas; Gupta, Sanjeev; Dabur, Rajesh; Injeti, Elisha; Mittal, Ashwani

    2015-09-01

    Over the last two decades, new insights into the etiology of skeletal muscle wasting/atrophy under diverse clinical settings including denervation, AIDS, cancer, diabetes, and chronic heart failure have been reported in the literature. However, the treatment of skeletal muscle wasting remains an unresolved challenge to this day. About nineteen potential drugs that can regulate loss of muscle mass have been reported in the literature. This paper reviews the mechanisms of action of all these drugs by broadly classifying them into six different categories. Mechanistic data of these drugs illustrate that they regulate skeletal muscle loss either by down-regulating myostatin, cyclooxygenase2, pro-inflammatory cytokines mediated catabolic wasting or by up-regulating cyclic AMP, peroxisome proliferator-activated receptor gamma coactivator-1α, growth hormone/insulin-like growth factor1, phosphatidylinositide 3-kinases/protein kinase B(Akt) mediated anabolic pathways. So far, five major proteolytic systems that regulate loss of muscle mass have been identified, but the majority of these drugs control only two or three proteolytic systems. In addition to their beneficial effect on restoring the muscle loss, many of these drugs show some level of toxicity and unwanted side effects such as dizziness, hypertension, and constipation. Therefore, further research is needed to understand and develop treatment strategies for muscle wasting. For successful management of skeletal muscle wasting either therapeutic agent which regulates all five known proteolytic systems or new molecular targets/proteolytic systems must be identified. PMID:26048279

  11. Multifocal fluorescence microscope for fast optical recordings of neuronal action potentials.

    PubMed

    Shtrahman, Matthew; Aharoni, Daniel B; Hardy, Nicholas F; Buonomano, Dean V; Arisaka, Katsushi; Otis, Thomas S

    2015-02-01

    In recent years, optical sensors for tracking neural activity have been developed and offer great utility. However, developing microscopy techniques that have several kHz bandwidth necessary to reliably capture optically reported action potentials (APs) at multiple locations in parallel remains a significant challenge. To our knowledge, we describe a novel microscope optimized to measure spatially distributed optical signals with submillisecond and near diffraction-limit resolution. Our design uses a spatial light modulator to generate patterned illumination to simultaneously excite multiple user-defined targets. A galvanometer driven mirror in the emission path streaks the fluorescence emanating from each excitation point during the camera exposure, using unused camera pixels to capture time varying fluorescence at rates that are ∼1000 times faster than the camera's native frame rate. We demonstrate that this approach is capable of recording Ca(2+) transients resulting from APs in neurons labeled with the Ca(2+) sensor Oregon Green Bapta-1 (OGB-1), and can localize the timing of these events with millisecond resolution. Furthermore, optically reported APs can be detected with the voltage sensitive dye DiO-DPA in multiple locations within a neuron with a signal/noise ratio up to ∼40, resolving delays in arrival time along dendrites. Thus, the microscope provides a powerful tool for photometric measurements of dynamics requiring submillisecond sampling at multiple locations. PMID:25650920

  12. Kv3.1 uses a timely resurgent K+ current to secure action potential repolarization

    PubMed Central

    Labro, Alain J.; Priest, Michael F.; Lacroix, Jérôme J.; Snyders, Dirk J.; Bezanilla, Francisco

    2015-01-01

    High-frequency action potential (AP) transmission is essential for rapid information processing in the central nervous system. Voltage-dependent Kv3 channels play an important role in this process thanks to their high activation threshold and fast closure kinetics, which reduce the neuron's refractory period. However, premature Kv3 channel closure leads to incomplete membrane repolarization, preventing sustainable AP propagation. Here, we demonstrate that Kv3.1b channels solve this problem by producing resurgent K+ currents during repolarization, thus ensuring enough repolarizing power to terminate each AP. Unlike previously described resurgent Na+ and K+ currents, Kv3.1b's resurgent current does not originate from recovery of channel block or inactivation but results from a unique combination of steep voltage-dependent gating kinetics and ultra-fast voltage-sensor relaxation. These distinct properties are readily transferrable onto an orthologue Kv channel by transplanting the voltage-sensor's S3–S4 loop, providing molecular insights into the mechanism by which Kv3 channels contribute to high-frequency AP transmission. PMID:26673941

  13. Glucocorticoids: mechanisms of action and anti-inflammatory potential in asthma.

    PubMed Central

    van der Velden, V H

    1998-01-01

    GLUCOCORTICOIDS are potent inhibitors of inflammatory processes and are widely used in the treatment of asthma. The anti-inflammatory effects are mediated either by direct binding of the glucocorticoid/glucocorticoid receptor complex to glucocorticoid responsive elements in the promoter region of genes, or by an interaction of this complex with other transcription factors, in particular activating protein-1 or nuclear factor-kappaB. Glucocorticoids inhibit many inflammation-associated molecules such as cytokines, chemokines, arachidonic acid metabolites, and adhesion molecules. In contrast, anti-inflammatory mediators often are up-regulated by glucocorticoids. In vivo studies have shown that treatment of asthmatic patients with inhaled glucocorticoids inhibits the bronchial inflammation and simultaneously improves their lung function. In this review, our current knowledge of the mechanism of action of glucocorticoids and their anti-inflammatory potential in asthma is described. Since bronchial epithelial cells may be important targets for glucocorticoid therapy in asthma, the effects of glucocorticoids on epithelial expressed inflammatory genes will be emphasized. PMID:9792333

  14. Do Resin Cements Alter Action Potentials of Isolated Rat Sciatic Nerve?

    PubMed Central

    Ertan, Ahmet Atila; Beriat, Nilufer Celebi; Onur, Mehmet Ali; Tan, Gamze; Cehreli, Murat Cavit

    2011-01-01

    Objectives: The purpose of this study was to explore the effects dual-cure resin cements on nerve conduction. Methods: Panavia F, RelyX ARC, and Variolink II polymerized either by light-emitting diode (LED) or quartz tungsten halogen (QTH) were used in the study (n=10). The conductance of sciatic nerves of 50 rats were measured before and after contact with the specimens for 1 h. Results: The time-dependent change in nerve conductance and the comparison of LED versus QTH showed that differences between groups are significant (P<.05). For both polymerization techniques, pair-wise comparisons of resin cements showed that the nerve conductance between groups is different (P<.05). RelyX ARC elicited irreversible inhibition of compound action potentials (more than 50% change) and Panavia F and Variolink II polymerized by LED and QTH did not alter nerve conduction beyond physiologic limits. Conclusions: Resin cements may alter nerve conductance and even lead to neurotoxic effects. PMID:21494389

  15. Sensitivity analysis of potential events affecting the double-shell tank system and fallback actions

    SciTech Connect

    Knutson, B.J.

    1996-09-27

    Sensitivity analyses were performed for fall-back positions (i.e., management actions) to accommodate potential off-normal and programmatic change events overlaid on the waste volume projections and their uncertainties. These sensitivity analyses allowed determining and ranking tank system high-risk parameters and fall- back positions that will accommodate the respective impacts. This quantification of tank system impacts shows periods where tank capacity is sensitive to certain variables that must be carefully managed and/or evaluated. Identifying these sensitive variables and quantifying their impact will allow decision makers to prepare fall-back positions and focus available resources on the highest impact parameters where technical data are needed to reduce waste projection uncertainties. For noncomplexed waste, the period of capacity vulnerability occurs during the years of single-shell tank (SST) retrieval (after approximately 2009) due to the sensitivity to several variables. Ranked by importance these variables include the pretreatment rate and 200-East SST solids transfer volume. For complexed waste, the period of capacity vulnerability occurs during the period after approximately 2005 due to the sensitivity to several variables. Ranked by importance these variables include the pretreatment rate. 200-East SST solids transfer volume. complexed waste reduction factor using evaporation, and 200-west saltwell liquid porosity.

  16. Motor Unit Number Estimation and Motor Unit Action Potential Analysis in Carpal Tunnel Syndrome

    PubMed Central

    Sohn, Min Kyun; Jee, Sung Ju; Kim, Young-Jae; Shin, Hyun-Dae

    2011-01-01

    Objective To evaluate the clinical significance of motor unit number estimation (MUNE) and quantitative analysis of motor unit action potential (MUAP) in carpal tunnel syndrome (CTS) according to electrophysiologic severity, ultrasonographic measurement and clinical symptoms. Method We evaluated 78 wrists of 45 patients, who had been diagnosed with CTS and 42 wrists of 21 healthy controls. Median nerve conduction studies, amplitude and duration of MUAP, and the MUNE of the abductor pollicis brevis were measured. The cross sectional area (CSA) of the median nerve at the pisiform and distal radioulnar joint level was determined by high resolution ultrasonography. Clinical symptom of CTS was assessed using the Boston Carpal Tunnel Questionnaire (BCTQ). Results The MUNE, the amplitude and the duration of MUAP of the CTS group were significantly different from those found in the control group. The area under the ROC curve was 0.944 for MUNE, 0.923 for MUAP amplitude and 0.953 for MUAP duration. MUNE had a negative correlation with electrophysiologic stage of CTS, amplitude and duration of MUAP, CSA at pisiform level, and the score of BCTQ. The amplitude and duration of MUAP had a positive correlation with the score of BCTQ. The electrophysiologic stage was correlated with amplitude but not with the duration of MUAP. Conclusion MUNE, amplitude and duration of MUAP are useful tests for diagnosis of CTS. In addition, the MUNE serves as a good indicator of CTS severity. PMID:22506210

  17. Efficacy of action potential simulation and interferential therapy in the rehabilitation of patients with knee osteoarthritis

    PubMed Central

    Eftekharsadat, Bina; Habibzadeh, Afshin; Kolahi, Babak

    2015-01-01

    Objective: Knee osteoarthritis (OA) is the main cause of pain, physical impairment and chronic disability in older people. Electrotherapeutic modalities such as interferential therapy (IFT) and action potential simulation (APS) are used for the treatment of knee OA. In this study, we aim to evaluate the therapeutic effects of APS and IFT on knee OA. Methods: In this randomized clinical trial, 67 patients (94% female and 6% male with mean age of 52.80 ± 8.16 years) with mild and moderate knee OA were randomly assigned to be treated with APS (n = 34) or IFT (n = 33) for 10 sessions in 4 weeks. Baseline and post-treatment Western Ontario and McMaster Universities Osteoarthritis (WOMAC) subscales, visual analogue scale (VAS) and timed up and go (TUG) test were measured in all patients. Results: VAS and WOMAC subscales were significantly improved after treatment in APS and IFT groups (p < 0.001 for all). TUG was also significantly improved after treatment in APS group (p < 0.001), but TUG changes in IFT was not significant (p = 0.09). There was no significant difference in VAS, TUG and WOMAC subscales values before and after treatment as well as the mean improvement in VAS, TUG and WOMAC subscales during study between groups. Conclusion: Short-term treatment with both APS and IFT could significantly reduce pain and improve physical function in patients with knee OA. PMID:26029268

  18. 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

  19. 'Action potential-like' ST elevation following pseudo-Wellens' electrocardiogram.

    PubMed

    Oksuz, Fatih; Sensoy, Baris; Sen, Fatih; Celik, Ethem; Ozeke, Ozcan; Maden, Orhan

    2015-01-01

    Coronary artery vasospasm is an important cause of chest pain syndromes that can lead to myocardial infarction, ventricular arrhythmias, and sudden death. In 1959, Prinzmetal et al described a syndrome of nonexertional chest pain with ST-segment elevation on electrocardiography. Persistent angina is challenging, and repeated coronary angioplasty may be required in this syndrome. Calcium antagonists are extremely effective in treating and preventing coronary spasm, and may provide long-lasting relief for the patient. Whereas the Wellens' syndrome is characterized by symmetrically inverted T-waves with preserved R waves in the precordial leads suggestive of impending myocardial infarction due to a critical proximal left anterior descending stenosis, the pseudo-Wellens' syndrome caused by coronary artery spasm has also rarely been reported in literature. We present a pseudo-Wellens syndrome as a cause of vasospastic angina, and a diffuse ST segment elavation on electrocardiogram resembling the Greek letter lambda, called also 'action potential-like' ECG in a patient with vasospastic-type Printzmetal angina. PMID:26432739

  20. A Hybrid Classifier for Characterizing Motor Unit Action Potentials in Diagnosing Neuromuscular Disorders

    PubMed Central

    Kamali, T; Boostani, R; Parsaei, H

    2013-01-01

    Background: The time and frequency features of motor unit action potentials (MUAPs) extracted from electromyographic (EMG) signal provide discriminative information for diagnosis and treatment of neuromuscular disorders. However, the results of conventional automatic diagnosis methods using MUAP features is not convincing yet. Objective: The main goal in designing a MUAP characterization system is obtaining high classification accuracy to be used in clinical decision system. For this aim, in this study, a robust classifier is proposed to improve MUAP classification performance in estimating the class label (myopathic, neuropathic and normal) of a given MUAP. Method: The proposed scheme employs both time and time–frequency features of a MUAP along with an ensemble of support vector machines (SVMs) classifiers in hybrid serial/parallel architecture. Time domain features includes phase, turn, peak to peak amplitude, area, and duration of the MUAP. Time–frequency features are discrete wavelet transform coefficients of the MUAP. Results: Evaluation results of the developed system using EMG signals of 23 subjects (7 with myopathic, 8 with neuropathic and 8 with no diseases)  showed that the system estimated the class label of MUAPs extracted from these signals with average of accuracy of 91% which is at least 5% higher than the accuracy of two previously presented methods. Conclusion: Using different optimized subsets of features along with the presented hybrid classifier results in a classification accuracy that is encouraging to be used in clinical applications for MUAP characterization.  PMID:25505761

  1. Motor unit action potential conduction velocity estimated from surface electromyographic signals using image processing techniques.

    PubMed

    Soares, Fabiano Araujo; Carvalho, João Luiz Azevedo; Miosso, Cristiano Jacques; de Andrade, Marcelino Monteiro; da Rocha, Adson Ferreira

    2015-01-01

    In surface electromyography (surface EMG, or S-EMG), conduction velocity (CV) refers to the velocity at which the motor unit action potentials (MUAPs) propagate along the muscle fibers, during contractions. The CV is related to the type and diameter of the muscle fibers, ion concentration, pH, and firing rate of the motor units (MUs). The CV can be used in the evaluation of contractile properties of MUs, and of muscle fatigue. The most popular methods for CV estimation are those based on maximum likelihood estimation (MLE). This work proposes an algorithm for estimating CV from S-EMG signals, using digital image processing techniques. The proposed approach is demonstrated and evaluated, using both simulated and experimentally-acquired multichannel S-EMG signals. We show that the proposed algorithm is as precise and accurate as the MLE method in typical conditions of noise and CV. The proposed method is not susceptible to errors associated with MUAP propagation direction or inadequate initialization parameters, which are common with the MLE algorithm. Image processing -based approaches may be useful in S-EMG analysis to extract different physiological parameters from multichannel S-EMG signals. Other new methods based on image processing could also be developed to help solving other tasks in EMG analysis, such as estimation of the CV for individual MUs, localization and tracking of innervation zones, and study of MU recruitment strategies. PMID:26384112

  2. Adhesion to Carbon Nanotube Conductive Scaffolds Forces Action-Potential Appearance in Immature Rat Spinal Neurons

    PubMed Central

    Toma, Francesca Maria; Calura, Enrica; Rizzetto, Lisa; Carrieri, Claudia; Roncaglia, Paola; Martinelli, Valentina; Scaini, Denis; Masten, Lara; Turco, Antonio; Gustincich, Stefano; Prato, Maurizio; Ballerini, Laura

    2013-01-01

    In the last decade, carbon nanotube growth substrates have been used to investigate neurons and neuronal networks formation in vitro when guided by artificial nano-scaled cues. Besides, nanotube-based interfaces are being developed, such as prosthesis for monitoring brain activity. We recently described how carbon nanotube substrates alter the electrophysiological and synaptic responses of hippocampal neurons in culture. This observation highlighted the exceptional ability of this material in interfering with nerve tissue growth. Here we test the hypothesis that carbon nanotube scaffolds promote the development of immature neurons isolated from the neonatal rat spinal cord, and maintained in vitro. To address this issue we performed electrophysiological studies associated to gene expression analysis. Our results indicate that spinal neurons plated on electro-conductive carbon nanotubes show a facilitated development. Spinal neurons anticipate the expression of functional markers of maturation, such as the generation of voltage dependent currents or action potentials. These changes are accompanied by a selective modulation of gene expression, involving neuronal and non-neuronal components. Our microarray experiments suggest that carbon nanotube platforms trigger reparative activities involving microglia, in the absence of reactive gliosis. Hence, future tissue scaffolds blended with conductive nanotubes may be exploited to promote cell differentiation and reparative pathways in neural regeneration strategies. PMID:23951361

  3. Kv3.1 uses a timely resurgent K(+) current to secure action potential repolarization.

    PubMed

    Labro, Alain J; Priest, Michael F; Lacroix, Jérôme J; Snyders, Dirk J; Bezanilla, Francisco

    2015-01-01

    High-frequency action potential (AP) transmission is essential for rapid information processing in the central nervous system. Voltage-dependent Kv3 channels play an important role in this process thanks to their high activation threshold and fast closure kinetics, which reduce the neuron's refractory period. However, premature Kv3 channel closure leads to incomplete membrane repolarization, preventing sustainable AP propagation. Here, we demonstrate that Kv3.1b channels solve this problem by producing resurgent K(+) currents during repolarization, thus ensuring enough repolarizing power to terminate each AP. Unlike previously described resurgent Na(+) and K(+) currents, Kv3.1b's resurgent current does not originate from recovery of channel block or inactivation but results from a unique combination of steep voltage-dependent gating kinetics and ultra-fast voltage-sensor relaxation. These distinct properties are readily transferrable onto an orthologue Kv channel by transplanting the voltage-sensor's S3-S4 loop, providing molecular insights into the mechanism by which Kv3 channels contribute to high-frequency AP transmission. PMID:26673941

  4. Multifocal Fluorescence Microscope for Fast Optical Recordings of Neuronal Action Potentials

    PubMed Central

    Shtrahman, Matthew; Aharoni, Daniel B.; Hardy, Nicholas F.; Buonomano, Dean V.; Arisaka, Katsushi; Otis, Thomas S.

    2015-01-01

    In recent years, optical sensors for tracking neural activity have been developed and offer great utility. However, developing microscopy techniques that have several kHz bandwidth necessary to reliably capture optically reported action potentials (APs) at multiple locations in parallel remains a significant challenge. To our knowledge, we describe a novel microscope optimized to measure spatially distributed optical signals with submillisecond and near diffraction-limit resolution. Our design uses a spatial light modulator to generate patterned illumination to simultaneously excite multiple user-defined targets. A galvanometer driven mirror in the emission path streaks the fluorescence emanating from each excitation point during the camera exposure, using unused camera pixels to capture time varying fluorescence at rates that are ∼1000 times faster than the camera’s native frame rate. We demonstrate that this approach is capable of recording Ca2+ transients resulting from APs in neurons labeled with the Ca2+ sensor Oregon Green Bapta-1 (OGB-1), and can localize the timing of these events with millisecond resolution. Furthermore, optically reported APs can be detected with the voltage sensitive dye DiO-DPA in multiple locations within a neuron with a signal/noise ratio up to ∼40, resolving delays in arrival time along dendrites. Thus, the microscope provides a powerful tool for photometric measurements of dynamics requiring submillisecond sampling at multiple locations. PMID:25650920

  5. A conceptual model for translating omic data into clinical action

    PubMed Central

    Herr, Timothy M.; Bielinski, Suzette J.; Bottinger, Erwin; Brautbar, Ariel; Brilliant, Murray; Chute, Christopher G.; Denny, Joshua; Freimuth, Robert R.; Hartzler, Andrea; Kannry, Joseph; Kohane, Isaac S.; Kullo, Iftikhar J.; Lin, Simon; Pathak, Jyotishman; Peissig, Peggy; Pulley, Jill; Ralston, James; Rasmussen, Luke; Roden, Dan; Tromp, Gerard; Williams, Marc S.; Starren, Justin

    2015-01-01

    Genomic, proteomic, epigenomic, and other “omic” data have the potential to enable precision medicine, also commonly referred to as personalized medicine. The volume and complexity of omic data are rapidly overwhelming human cognitive capacity, requiring innovative approaches to translate such data into patient care. Here, we outline a conceptual model for the application of omic data in the clinical context, called “the omic funnel.” This model parallels the classic “Data, Information, Knowledge, Wisdom pyramid” and adds context for how to move between each successive layer. Its goal is to allow informaticians, researchers, and clinicians to approach the problem of translating omic data from bench to bedside, by using discrete steps with clearly defined needs. Such an approach can facilitate the development of modular and interoperable software that can bring precision medicine into widespread practice. PMID:26430534

  6. A conceptual model for translating omic data into clinical action.

    PubMed

    Herr, Timothy M; Bielinski, Suzette J; Bottinger, Erwin; Brautbar, Ariel; Brilliant, Murray; Chute, Christopher G; Denny, Joshua; Freimuth, Robert R; Hartzler, Andrea; Kannry, Joseph; Kohane, Isaac S; Kullo, Iftikhar J; Lin, Simon; Pathak, Jyotishman; Peissig, Peggy; Pulley, Jill; Ralston, James; Rasmussen, Luke; Roden, Dan; Tromp, Gerard; Williams, Marc S; Starren, Justin

    2015-01-01

    Genomic, proteomic, epigenomic, and other "omic" data have the potential to enable precision medicine, also commonly referred to as personalized medicine. The volume and complexity of omic data are rapidly overwhelming human cognitive capacity, requiring innovative approaches to translate such data into patient care. Here, we outline a conceptual model for the application of omic data in the clinical context, called "the omic funnel." This model parallels the classic "Data, Information, Knowledge, Wisdom pyramid" and adds context for how to move between each successive layer. Its goal is to allow informaticians, researchers, and clinicians to approach the problem of translating omic data from bench to bedside, by using discrete steps with clearly defined needs. Such an approach can facilitate the development of modular and interoperable software that can bring precision medicine into widespread practice. PMID:26430534

  7. Electrostatic potential map modelling with COSY Infinity

    NASA Astrophysics Data System (ADS)

    Maloney, J. A.; Baartman, R.; Planche, T.; Saminathan, S.

    2016-06-01

    COSY Infinity (Makino and Berz, 2005) is a differential-algebra based simulation code which allows accurate calculation of transfer maps to arbitrary order. COSY's existing internal procedures were modified to allow electrostatic elements to be specified using an array of field potential data from the midplane. Additionally, a new procedure was created allowing electrostatic elements and their fringe fields to be specified by an analytic function. This allows greater flexibility in accurately modelling electrostatic elements and their fringe fields. Applied examples of these new procedures are presented including the modelling of a shunted electrostatic multipole designed with OPERA, a spherical electrostatic bender, and the effects of different shaped apertures in an electrostatic beam line.

  8. Optical-model potential in a relativistic quantum field model

    NASA Astrophysics Data System (ADS)

    Jaminon, M.; Mahaux, C.; Rochus, P.

    1980-11-01

    The average nucleon-nucleus potential at low and medium energy is investigated in the framework of a relativistic quantum field model. Using the same input parameters as Brockmann in his recent study of nuclear ground states, we calculate the self-consistent relativistic Hartree potential at positive energy in the case of infinite nuclear matter and of 16O and 40Ca. This potential is the sum of a scalar operator and of the fourth component of a vector operator. We construct its Schrödinger-equivalent potential by eliminating the small component of the Dirac spinor. The central part of this Schrödinger-equivalent potential is in fair agreement with empirical values at low and intermediate energy. Particular attention is paid to the intermediate energy domain, in which the calculated potential is repulsive in the nuclear interior and attractive at the nuclear surface. This is in keeping with some empirical evidence and is similar to results found in the framework of the nonrelativistic Brueckner-Hartree-Fock approximation. The spin-orbit potential of the relativistic Hartree model is also in good agreement with empirical values. NUCLEAR REACTIONS Calculated average nuclear field of nuclear matter, 16O and 40Ca at positive energy from relativistic Hartree approximation.

  9. 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

  10. Modelling Dowel Action of Discrete Reinforcing Bars in Cracked Concrete Structures

    SciTech Connect

    Kwan, A. K. H.; Ng, P. L.; Lam, J. Y. K.

    2010-05-21

    Dowel action is one of the component actions for shear force transfer in cracked reinforced concrete. In finite element analysis of concrete structures, the use of discrete representation of reinforcing bars is considered advantageous over the smeared representation due to the relative ease of modelling the bond-slip behaviour. However, there is very limited research on how to simulate the dowel action of discrete reinforcing bars. Herein, a numerical model for dowel action of discrete reinforcing bars crossing cracks in concrete is developed. The model features the derivation of dowel stiffness matrix based on beam-on-elastic-foundation theory and the direct assemblage of dowel stiffness into the concrete element stiffness matrices. The dowel action model is incorporated in a nonlinear finite element programme with secant stiffness formulation. Deep beams tested in the literature are analysed and it is found that the incorporation of dowel action model improves the accuracy of analysis.

  11. Toxicity, sublethal effects, and potential modes of action of select fungicides on freshwater fish and invertebrates

    USGS Publications Warehouse

    Elskus, Adria A.

    2012-01-01

    Despite decades of agricultural and urban use of fungicides and widespread detection of these pesticides in surface waters, relatively few data are available on the effects of fungicides on fish and invertebrates in the aquatic environment. Nine fungicides are reviewed in this report: azoxystrobin, boscalid, chlorothalonil, fludioxonil, myclobutanil, fenarimol, pyraclostrobin, pyrimethanil, and zoxamide. These fungicides were identified as emerging chemicals of concern because of their high or increasing global use rates, detection frequency in surface waters, or likely persistence in the environment. A review of the literature revealed significant sublethal effects of fungicides on fish, aquatic invertebrates, and ecosystems, including zooplankton and fish reproduction, fish immune function, zooplankton community composition, metabolic enzymes, and ecosystem processes, such as leaf decomposition in streams, among other biological effects. Some of these effects can occur at fungicide concentrations well below single-species acute lethality values (48- or 96-hour concentration that effects a response in 50 percent of the organisms, that is, effective concentration killing 50 percent of the organisms in 48 or 96 hours) and chronic sublethal values (for example, 21-day no observed adverse effects concentration), indicating that single-species toxicity values may dramatically underestimate the toxic potency of some fungicides. Fungicide modes of toxic action in fungi can sometimes reflect the biochemical and (or) physiological effects of fungicides observed in vertebrates and invertebrates; however, far more studies are needed to explore the potential to predict effects in nontarget organisms based on specific fungicide modes of toxic action. Fungicides can also have additive and (or) synergistic effects when used with other fungicides and insecticides, highlighting the need to study pesticide mixtures that occur in surface waters. For fungicides that partition to

  12. 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

  13. 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.…

  14. Action Algebras and Model Algebras in Denotational Semantics

    NASA Astrophysics Data System (ADS)

    Guedes, Luiz Carlos Castro; Haeusler, Edward Hermann

    code for arrays in the same way as that for functional denotational types. For example, PASCAL arrays belong to the “language inherent” aspect, while the Store domain seems to belong to the “model dependent” aspect. This distinction was important because it focussed attention on optimizing the model dependent semantic domains to obtain a more efficient implementation.) The research led to a nice conclusion: The guidelines of Action Semantics induce a clear separation of the model and language inherent aspects of a language’s semantics. A good implementation of facets, particularly the model dependent ones, leads to generation of an efficient compiler. In this article we discuss the separation of the language inherent and model-inherent domains at the theoretical and conceptual level. In doing so, the authors hope to show how Professor Mosses’s influence extended beyond his technical advice to his professional and personal examples on the supervision of PhD research.

  15. Bacteriocins: modes of action and potentials in food preservation and control of food poisoning.

    PubMed

    Abee, T; Krockel, L; Hill, C

    1995-12-01

    Lactic acid bacteria (LAB) play an essential role in the majority of food fermentations, and a wide variety of strains are routinely employed as starter cultures in the manufacture of dairy, meat, vegetable and bakery products. One of the most important contributions of these microorganisms is the extended shelf life of the fermented product by comparison to that of the raw substrate. Growth of spoilage and pathogenic bacteria in these foods is inhibited due to competition for nutrients and the presence of starter-derived inhibitors such as lactic acid, hydrogen peroxide and bacteriocins (Ray and Daeschel, 1992). Bacteriocins, are a heterogenous group of anti-bacterial proteins that vary in spectrum of activity, mode of action, molecular weight, genetic origin and biochemical properties. Currently, artificial chemical preservatives are employed to limit the number of microorganisms capable of growing within foods, but increasing consumer awareness of potential health risks associated with some of these substances has led researchers to examine the possibility of using bacteriocins produced by LAB as biopreservatives. The major classes of bacteriocins produced by LAB include: (I) lantibiotics, (II) small heat stable peptides, (III) large heat labile proteins, and (IV) complex proteins whose activity requires the association of carbohydrate or lipid moieties (Klaenhammer, 1993). Significantly however, the inhibitory activity of these substances is confined to Gram-positive bacteria and inhibition of Gram-negatives by these bacteriocins has not been demonstrated, an observation which can be explained by a detailed analysis and comparison of the composition of Gram-positive and Gram-negative bacterial cell walls (Fig. 1). In both types the cytoplasmic membrane which forms the border between the cytoplasm and the external environment, is surrounded by a layer of peptidoglycan which is significantly thinner in Gram-negative bacteria than in Gram-positive bacteria. Gram

  16. Effect of temperature on isoprenaline- and barium-induced slow action potentials in guinea-pig ventricular strips.

    PubMed

    Manzini, S; Parlani, M; Martucci, E; Maggi, C A; Meli, A

    1986-01-01

    The effect of variation in temperature (37-32 and 27 degrees C) on electrical and mechanical activity of depolarized and isoprenaline- or barium-reactivated guinea pig ventricular strips was studied. Lowering the temperature brings a marked prolongation of isoprenaline-induced slow action potentials. In addition the maximal rate of depolarization was strongly reduced at lower temperatures. These effects were observed at an extracellular Ca2+ concentration of either 0.9 or 2.5 mM. The accompanying mechanical activities was significantly increased by reduction in temperature. Barium-induced slow action potentials were similarly affected by temperature variations. These observations suggest that hypothermia exert a sort of calcium antagonistic action probably coupled to a reduction of repolarizing outward potassium currents. PMID:2430855

  17. Effect of knockout of α2δ-1 on action potentials in mouse sensory neurons.

    PubMed

    Margas, Wojciech; Ferron, Laurent; Nieto-Rostro, Manuela; Schwartz, Arnold; Dolphin, Annette C

    2016-08-01

    Gene deletion of the voltage-gated calcium channel auxiliary subunit α2δ-1 has been shown previously to have a cardiovascular phenotype, and a reduction in mechano- and cold sensitivity, coupled with delayed development of neuropathic allodynia. We have also previously shown that dorsal root ganglion (DRG) neuron calcium channel currents were significantly reduced in α2δ-1 knockout mice. To extend our findings in these sensory neurons, we have examined here the properties of action potentials (APs) in DRG neurons from α2δ-1 knockout mice in comparison to their wild-type (WT) littermates, in order to dissect how the calcium channels that are affected by α2δ-1 knockout are involved in setting the duration of individual APs and their firing frequency. Our main findings are that there is reduced Ca(2+) entry on single AP stimulation, particularly in the axon proximal segment, reduced AP duration and reduced firing frequency to a 400 ms stimulation in α2δ-1 knockout neurons, consistent with the expected role of voltage-gated calcium channels in these events. Furthermore, lower intracellular Ca(2+) buffering also resulted in reduced AP duration, and a lower frequency of AP firing in WT neurons, mimicking the effect of α2δ-1 knockout. By contrast, we did not obtain any consistent evidence for the involvement of Ca(2+)-activation of large conductance calcium-activated potassium (BK) and small conductance calcium-activated potassium (SK) channels in these events. In conclusion, the reduced Ca(2+) elevation as a result of single AP stimulation is likely to result from the reduced duration of the AP in α2δ-1 knockout sensory neurons.This article is part of the themed issue 'Evolution brings Ca(2+) and ATP together to control life and death'. PMID:27377724

  18. Effect of knockout of α2δ-1 on action potentials in mouse sensory neurons

    PubMed Central

    Margas, Wojciech; Ferron, Laurent; Nieto-Rostro, Manuela; Schwartz, Arnold; Dolphin, Annette C.

    2016-01-01

    Gene deletion of the voltage-gated calcium channel auxiliary subunit α2δ-1 has been shown previously to have a cardiovascular phenotype, and a reduction in mechano- and cold sensitivity, coupled with delayed development of neuropathic allodynia. We have also previously shown that dorsal root ganglion (DRG) neuron calcium channel currents were significantly reduced in α2δ-1 knockout mice. To extend our findings in these sensory neurons, we have examined here the properties of action potentials (APs) in DRG neurons from α2δ-1 knockout mice in comparison to their wild-type (WT) littermates, in order to dissect how the calcium channels that are affected by α2δ-1 knockout are involved in setting the duration of individual APs and their firing frequency. Our main findings are that there is reduced Ca2+ entry on single AP stimulation, particularly in the axon proximal segment, reduced AP duration and reduced firing frequency to a 400 ms stimulation in α2δ-1 knockout neurons, consistent with the expected role of voltage-gated calcium channels in these events. Furthermore, lower intracellular Ca2+ buffering also resulted in reduced AP duration, and a lower frequency of AP firing in WT neurons, mimicking the effect of α2δ-1 knockout. By contrast, we did not obtain any consistent evidence for the involvement of Ca2+-activation of large conductance calcium-activated potassium (BK) and small conductance calcium-activated potassium (SK) channels in these events. In conclusion, the reduced Ca2+ elevation as a result of single AP stimulation is likely to result from the reduced duration of the AP in α2δ-1 knockout sensory neurons. This article is part of the themed issue ‘Evolution brings Ca2+ and ATP together to control life and death’. PMID:27377724

  19. Halothane diminishes changes in cardiac fiber action potential duration induced by hypocarbia and hypercarbia.

    PubMed

    Stowe, D F; Bosnjak, Z J; Kampine, J P

    1984-09-01

    Both halothane (HAL) and acid-base changes produce cardiac arrhythmias in humans. The authors' aim was to determine if HAL alters the effects of hypercapnic acidosis and hypocapnic alkalosis on action potential (AP) properties of ventricular muscle fibers. They superfused the paced right ventricle of 15 guinea pig hearts with non-HCO3- buffered salt solution and recorded transmembrane APs with 3 M KCl microelectrodes in 35 subendocardial cells. Random changes in the fractions of HAL were made during low (12% CO2 in O2), normal (5% CO2 in O2), and high (0% CO2 in O2) pH. Compared with controls at pH 7.44, AP duration (APD) and effective refractory period (ERP) significantly decreased by 7 and 4% at pH 8.08 and increased by 7 and 9% at pH 7.09. At pH 7.44, 0.7-2.1% HAL produced no change in APD; but 2.1% increased ERP, while 3.5% HAL decreased ERP. At pH 8.08, the decrease in ERP induced with alkalosis alone was converted to an increase with 1.4 and 2.1% HAL. At pH 7.09, 0.7-1.4% HAL had no additional effect on the acidosis-induced increases in APD and ERP, but 2.1 and 2.8% HAL greatly reduced these responses. At HAL fractions greater than 1.4% the marked inverse changes in APD and ERP, induced alone by acidosis and alkalosis, were no longer significantly different from control. This study shows that the opposing effects of alkalosis to shorten and of acidosis to lengthen APD and ERP were attenuated at low levels and abolished at high levels of HAL.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:6433748

  20. Natural cures for type 1 diabetes: a review of phytochemicals, biological actions, and clinical potential.

    PubMed

    Chang, C L T; Chen, Yi-Ching; Chen, Hui-Ming; Yang, Ning-Sun; Yang, Wen-Chin

    2013-01-01

    Autoimmune diseases are the third largest category of illness in the industrialized world, following cardiovascular diseases and cancers. Among them, type 1 diabetes, also named autoimmune diabetes, afflicts 10 million people worldwide. This disease is caused by autoimmunity-mediated destruction of pancreatic β-cells, leading to insulin deficiency, hyperglycemia and complications. Currently, there is no cure for type 1 diabetes. Insulin injection is the only medication; however, it accompanies serious medical complications. Current strategies to cure type 1 diabetes include immunotherapy, replacement therapy, and combination therapy. Despite recent advances in anti-diabetic strategies, no strategy is clinically successful. How to cure type 1 diabetes without undesirable side effects still remains a formidable challenge in drug research and development. Plants provide an extraordinary source of natural medicines for different diseases. Moreover, secondary metabolites of plant origin serve as an invaluable chemical library for drug discovery and current medicinal chemistry in the pharmaceutical industry. Over the past 25 years, 50% of prescription drugs have been developed from natural products and their derivatives. In this article, we review more than 20 plant compounds and extracts reported in the literature to prevent and treat type-1 diabetes. Emphasis is placed on their chemistry and biology in terms of regulation of immune cells and pancreatic β-cells. We summarize recent progress in understanding the biological actions, mechanisms and therapeutic potential of the compounds and extracts of plant origin in type 1 diabetes. New views on phytocompound-based strategies for prevention and treatment of type 1 diabetes are also discussed. PMID:23210779

  1. A potential role for cannabinoid receptors in the therapeutic action of fenofibrate.

    PubMed

    Priestley, Richard S; Nickolls, Sarah A; Alexander, Stephen P H; Kendall, David A

    2015-04-01

    Cannabinoids are reported to have actions through peroxisome proliferator-activated receptors (PPARs), which led us to investigate PPAR agonists for activity at the cannabinoid receptors. Radio-ligand binding and functional assays were conducted using human recombinant cannabinoid type 1 (CB1) or cannabinoid type 2 (CB2) receptors, as well as the guinea pig isolated ileum, using the full agonist CP55940 as a positive control. The PPAR-α agonist fenofibrate exhibited submicromolar affinity for both receptors (pKi CB1, 6.3 ± 0.1; CB2, 7.7 ± 0.1). Functionally, fenofibrate acted as an agonist at the CB2 receptor (pEC50, 7.7 ± 0.1) and a partial agonist at the CB1 receptor, although with a decrease in functional response at higher concentrations, producing bell-shaped concentration-response curves. High concentrations of fenofibrate were able to increase the dissociation rate constant for [(3)H]-CP55940 at the CB1 receptor, (kfast without: 1.2 ± 0.2/min; with: 3.8 ± 0.1 × 10(-2)/min) and decrease the maximal response to CP55940 (Rmax, 86 ± 2%), which is consistent with a negative allosteric modulator. Fenofibrate also reduced electrically induced contractions in isolated guinea pig ileum via CB1 receptors (pEC50, 6.0 ± 0.4). Fenofibrate is thus identified as an example of a new class of cannabinoid receptor ligand and allosteric modulator, with the potential to interact therapeutically with cannabinoid receptors in addition to its primary PPAR target. PMID:25550466

  2. Contribution of auditory nerve fibers to compound action potential of the auditory nerve.

    PubMed

    Bourien, Jérôme; Tang, Yong; Batrel, Charlène; Huet, Antoine; Lenoir, Marc; Ladrech, Sabine; Desmadryl, Gilles; Nouvian, Régis; Puel, Jean-Luc; Wang, Jing

    2014-09-01

    Sound-evoked compound action potential (CAP), which captures the synchronous activation of the auditory nerve fibers (ANFs), is commonly used to probe deafness in experimental and clinical settings. All ANFs are believed to contribute to CAP threshold and amplitude: low sound pressure levels activate the high-spontaneous rate (SR) fibers, and increasing levels gradually recruit medium- and then low-SR fibers. In this study, we quantitatively analyze the contribution of the ANFs to CAP 6 days after 30-min infusion of ouabain into the round window niche. Anatomic examination showed a progressive ablation of ANFs following increasing concentration of ouabain. CAP amplitude and threshold plotted against loss of ANFs revealed three ANF pools: 1) a highly ouabain-sensitive pool, which does not participate in either CAP threshold or amplitude, 2) a less sensitive pool, which only encoded CAP amplitude, and 3) a ouabain-resistant pool, required for CAP threshold and amplitude. Remarkably, distribution of the three pools was similar to the SR-based ANF distribution (low-, medium-, and high-SR fibers), suggesting that the low-SR fiber loss leaves the CAP unaffected. Single-unit recordings from the auditory nerve confirmed this hypothesis and further showed that it is due to the delayed and broad first spike latency distribution of low-SR fibers. In addition to unraveling the neural mechanisms that encode CAP, our computational simulation of an assembly of guinea pig ANFs generalizes and extends our experimental findings to different species of mammals. Altogether, our data demonstrate that substantial ANF loss can coexist with normal hearing threshold and even unchanged CAP amplitude. PMID:24848461

  3. Shade-Induced Action Potentials in Helianthus annuus L. Originate Primarily from the Epicotyl

    PubMed Central

    Stephens, Nicholas R; Cleland, Robert E; Van Volkenburgh, Elizabeth

    2006-01-01

    Repeated observations that shading (a drastic reduction in illumination rate) increased the generation of spikes (rapidly reversed depolarizations) in leaves and stems of many cucumber and sunflower plants suggests a phenomenon widespread among plant organs and species. Although shaded leaves occasionally generate spikes and have been suggested to trigger systemic action potentials (APs) in sunflower stems, we never found leaf-generated spikes to propagate out of the leaf and into the stem. On the contrary, our data consistently implicate the epicotyl as the location where most spikes and APs (propagating spikes) originate. Microelectrode studies of light and shading responses in mesophyll cells of leaf strips and in epidermis/cortex cells of epicotyl segments confirm this conclusion and show that spike induction is not confined to intact plants. 90% of the epicotyl-generated APs undergo basipetal propagation to the lower epicotyl, hypocotyl and root. They propagate with an average rate of 2 ± 0.3 mm s−1 and always undergo a large decrement from the hypocotyl to the root. The few epicotyl-derived APs that can be tracked to leaf blades (< 10%) undergo either a large decrement or fail to be transmitted at all. Occasionally (5% of the observations) spikes were be generated in hypocotyl and lower epicotyl that moved towards the upper epicotyl unaltered, decremented, or amplified. This study confirms that plant APs arise to natural, nontraumatic changes. In simultaneous recordings with epicotyl growth, AP generation was found to parallel the acceleration of stem growth under shade. The possible relatedness of both processes must be further investigated. PMID:19521471

  4. Disruption of action potential and calcium signaling properties in malformed myofibers from dystrophin-deficient mice

    PubMed Central

    Hernández-Ochoa, Erick O; Pratt, Stephen J P; Garcia-Pelagio, Karla P; Schneider, Martin F; Lovering, Richard M

    2015-01-01

    Duchenne muscular dystrophy (DMD), the most common and severe muscular dystrophy, is caused by the absence of dystrophin. Muscle weakness and fragility (i.e., increased susceptibility to damage) are presumably due to structural instability of the myofiber cytoskeleton, but recent studies suggest that the increased presence of malformed/branched myofibers in dystrophic muscle may also play a role. We have previously studied myofiber morphology in healthy wild-type (WT) and dystrophic (MDX) skeletal muscle. Here, we examined myofiber excitability using high-speed confocal microscopy and the voltage-sensitive indicator di-8-butyl-amino-naphthyl-ethylene-pyridinium-propyl-sulfonate (di-8-ANEPPS) to assess the action potential (AP) properties. We also examined AP-induced Ca2+ transients using high-speed confocal microscopy with rhod-2, and assessed sarcolemma fragility using elastimetry. AP recordings showed an increased width and time to peak in malformed MDX myofibers compared to normal myofibers from both WT and MDX, but no significant change in AP amplitude. Malformed MDX myofibers also exhibited reduced AP-induced Ca2+ transients, with a further Ca2+ transient reduction in the branches of malformed MDX myofibers. Mechanical studies indicated an increased sarcolemma deformability and instability in malformed MDX myofibers. The data suggest that malformed myofibers are functionally different from myofibers with normal morphology. The differences seen in AP properties and Ca2+ signals suggest changes in excitability and remodeling of the global Ca2+ signal, both of which could underlie reported weakness in dystrophic muscle. The biomechanical changes in the sarcolemma support the notion that malformed myofibers are more susceptible to damage. The high prevalence of malformed myofibers in dystrophic muscle may contribute to the progressive strength loss and fragility seen in dystrophic muscles. PMID:25907787

  5. The effect of stimulation frequency on the transmural ventricular monophasic action potential in yellowfin tuna Thunnus albacares.

    PubMed

    Patrick, S M; White, E; Brill, R W; Shiels, H A

    2011-02-01

    Monophasic action potentials (MAPs) were recorded from the spongy and compact layers of the yellowfin tuna Thunnus albacares ventricle as stimulation frequency was increased. MAP duration decreased with increase in stimulation frequency in both the spongy and compact myocardial layers, but no significant difference in MAP duration was observed between the layers. PMID:21284642

  6. Anti-atherogenic potential of jujube, saffron and barberry: anti-diabetic and antioxidant actions.

    PubMed

    Hemmati, Mina; Zohoori, Elham; Mehrpour, Omid; Karamian, Mehdi; Asghari, Somaye; Zarban, Asghar; Nasouti, Roya

    2015-01-01

    Atherogenic dyslipidemia, characterized by an increased level of lipoprotein (a) and a decreased level of adiponectin, is a major risk factor for cardiovascular diseases in diabetic patients. To reduce cardiovascular risk in diabetic patients, use of agents with antidiabetic and anti-atherogenic potential is required. Using an animal model of diabetes, we investigated the antiatherogenic potential of extracts of three medicinal plants: jujube, barberry, and saffron. For this, serum level of fasting blood glucose, lipid profile, malondialdehyde, total antioxidant capacity, adiponectin and lipoprotein (a) in diabetic control and extract treated groups were measured. Statistical analysis of measurements showed that serum levels of fasting blood glucose, triglyceride, and VLDL decreased significantly (P < 0.05) in all treated groups. Treatment with all extracts reduced lipid peroxidation and increased antioxidant capacity of the experimental diabetic groups. Serum adiponectin levels increased in all treated groups, whereas lipoprotein (a) levels decreased, most markedly when treated with jujube extract. Jujube, saffron, and barberry extracts are beneficial in ameliorating oxidative stress and atherogenic risk of diabetic rats. This highlights the benefits of further investigating the cardio-protective potential of medicinal plant extracts and evaluating their usefulness as cardio protective agents in clinical practice. PMID:26600752

  7. Egyptian exploration: background, models, and future potential

    SciTech Connect

    Kanes, W.H.; Abdine, S.

    1983-03-01

    Egypt has proven to be an area with excelllnt exploration potential. Recent discoveries in the Western Desert tilted fault blocks are leading to a reevaluation of new play concepts based on an east-west Tethyan rift structure model. Facies favorable to hydrocarbon accumulation are associated with shallow-water marine depositional environments. Production has not been great on a per-well basis, but fields have consistently out-produced the original recoverable reserve estimates. The Gulf of Suez lies within the rift between North Africa and Arabia-Sinai. It remains a major producing area with production from sandstones which range in age from Carboniferous to Cretaceous. The Upper Cretaceous and Lower Tertiary carbonates are potentially attractive zones, as are the Miocene clastics and carbonates. Miocene marls and Upper Cretaceous shales are source rocks, and thermal maturation can be directly related to continental rifting with the oil window most attractive in the southern third of the Gulf of Suez. Structural style is strongly rift-influenced with tilted and locally eroded hosts prevalent. The central gulf has a general eastern dip, whereas the northern and southern areas have a regional westward dip. This has had a direct influence in isolating some major oil fields and has adversely affected reflection seismic surveys. Exploration has been difficult because of excessive Miocene and younger salt thicknesses. With increasingly refined technology, attractive targets now are being delineated in the hitherto unexplored lows between horsts within the gulf.

  8. The energy cost of action potential propagation in dopamine neurons: clues to susceptibility in Parkinson's disease

    PubMed Central

    Pissadaki, Eleftheria K.; Bolam, J. Paul

    2013-01-01

    Dopamine neurons of the substantia nigra pars compacta (SNc) are uniquely sensitive to degeneration in Parkinson's disease (PD) and its models. Although a variety of molecular characteristics have been proposed to underlie this sensitivity, one possible contributory factor is their massive, unmyelinated axonal arbor that is orders of magnitude larger than other neuronal types. We suggest that this puts them under such a high energy demand that any stressor that perturbs energy production leads to energy demand exceeding supply and subsequent cell death. One prediction of this hypothesis is that those dopamine neurons that are selectively vulnerable in PD will have a higher energy cost than those that are less vulnerable. We show here, through the use of a biology-based computational model of the axons of individual dopamine neurons, that the energy cost of axon potential propagation and recovery of the membrane potential increases with the size and complexity of the axonal arbor according to a power law. Thus SNc dopamine neurons, particularly in humans, whose axons we estimate to give rise to more than 1 million synapses and have a total length exceeding 4 m, are at a distinct disadvantage with respect to energy balance which may be a factor in their selective vulnerability in PD. PMID:23515615

  9. Redox-active compounds with a history of human use: antistaphylococcal action and potential for repurposing as topical antibiofilm agents

    PubMed Central

    Ooi, N.; Eady, E. A.; Cove, J. H.; O'Neill, A. J.

    2015-01-01

    Objectives To investigate the antistaphylococcal/antibiofilm activity and mode of action (MOA) of a panel of redox-active (RA) compounds with a history of human use and to provide a preliminary preclinical assessment of their potential for topical treatment of staphylococcal infections, including those involving a biofilm component. Methods Antistaphylococcal activity was evaluated by broth microdilution and by time–kill studies with growing and slow- or non-growing cells. The antibiofilm activity of RA compounds, alone and in combination with established antibacterial agents, was assessed using the Calgary Biofilm Device. Established assays were used to examine the membrane-perturbing effects of RA compounds, to measure penetration into biofilms and physical disruption of biofilms and to assess resistance potential. A living skin equivalent model was used to assess the effects of RA compounds on human skin. Results All 15 RA compounds tested displayed antistaphylococcal activity against planktonic cultures (MIC 0.25–128 mg/L) and 7 eradicated staphylococcal biofilms (minimum biofilm eradication concentration 4–256 mg/L). The MOA of all compounds involved perturbation of the bacterial membrane, whilst selected compounds with antibiofilm activity caused destructuring of the biofilm matrix. The two most promising agents [celastrol and nordihydroguaiaretic acid (NDGA)] in respect of antibacterial potency and selective toxicity against bacterial membranes acted synergistically with gentamicin against biofilms, did not damage artificial skin following topical application and exhibited low resistance potential. Conclusions In contrast to established antibacterial drugs, some RA compounds are capable of eradicating staphylococcal biofilms. Of these, celastrol and NDGA represent particularly attractive candidates for development as topical antistaphylococcal biofilm treatments. PMID:25368206

  10. Action potential characterization of human induced pluripotent stem cell-derived cardiomyocytes using automated patch-clamp technology.

    PubMed

    Scheel, Olaf; Frech, Stefanie; Amuzescu, Bogdan; Eisfeld, Jörg; Lin, Kun-Han; Knott, Thomas

    2014-10-01

    Recent progress in embryonic stem cell (ESC) and induced pluripotent stem cell (iPSC) research led to high-purity preparations of human cardiomyocytes (CMs) differentiated from these two sources-suitable for tissue regeneration, in vitro models of disease, and cardiac safety pharmacology screening. We performed a detailed characterization of the effects of nifedipine, cisapride, and tetrodotoxin (TTX) on Cor.4U(®) human iPSC-CM, using automated whole-cell patch-clamp recordings with the CytoPatch™ 2 equipment, within a complex assay combining multiple voltage-clamp and current-clamp protocols in a well-defined sequence, and quantitative analysis of several action potential (AP) parameters. We retrieved three electrical phenotypes based on AP shape: ventricular, atrial/nodal, and S-type (with ventricular-like depolarization and lack of plateau). To suppress spontaneous firing, present in many cells, we injected continuously faint hyperpolarizing currents of -10 or -20 pA. We defined quality criteria (both seal and membrane resistance over 1 GΩ), and focused our study on cells with ventricular-like AP. Nifedipine induced marked decreases in AP duration (APD): APD90 (49.8% and 40.8% of control values at 1 and 10 μM, respectively), APD50 (16.1% and 12%); cisapride 0.1 μM increased APD90 to 176.2%; and tetrodotoxin 10 μM decreased maximum slope of phase to 33.3% of control, peak depolarization potential to 76.3% of control, and shortened APD90 on average to 80.4%. These results prove feasibility of automated voltage- and current-clamp recordings on human iPSC-CM and their potential use for in-depth drug evaluation and proarrhythmic liability assessment, as well as for diagnosis and pharmacology tests for cardiac channelopathy patients. PMID:25353059

  11. Radiolysis Model Formulation for Integration with the Mixed Potential Model

    SciTech Connect

    Buck, Edgar C.; Wittman, Richard S.

    2014-07-10

    The U.S. Department of Energy Office of Nuclear Energy (DOE-NE), Office of Fuel Cycle Technology has established the Used Fuel Disposition Campaign (UFDC) to conduct the research and development activities related to storage, transportation, and disposal of used nuclear fuel (UNF) and high-level radioactive waste. Within the UFDC, the components for a general system model of the degradation and subsequent transport of UNF is being developed to analyze the performance of disposal options [Sassani et al., 2012]. Two model components of the near-field part of the problem are the ANL Mixed Potential Model and the PNNL Radiolysis Model. This report is in response to the desire to integrate the two models as outlined in [Buck, E.C, J.L. Jerden, W.L. Ebert, R.S. Wittman, (2013) “Coupling the Mixed Potential and Radiolysis Models for Used Fuel Degradation,” FCRD-UFD-2013-000290, M3FT-PN0806058

  12. Elucidation of possible mechanism of analgesic action of Valeriana wallichii DC chemotype (patchouli alcohol) in experimental animal models.

    PubMed

    Sah, Sangeeta Pilkhwal; Mathela, Chandra S; Chopra, Kanwaljit

    2010-03-01

    Valeriana wallichii (Family Valerianaceae), popularly named as Indian valerian, exists as three chemotypes. Aim of the study was to evaluate the effect of V. wallichii chemotype (patchouli alcohol) extract (DCME) and essential oil (VPAEO) on experimental models of nociception and to elucidate its possible mechanism of action. Analgesic effect was evaluated using acetic acid induced writhing and tail flick model. DCME and VPAEO (40 and 80 mg/kg, p.o.) significantly inhibited the number of writhings as compared to vehicle treated group. None of the doses of DCME and VPAEO exhibited any effect in tail flick model suggesting only peripheral analgesic activity. When studied for mechanism of action in acetic acid induced writhing, subeffective dose of essential oil significantly potentiated the effect of aspirin while no potentiation was seen in case of extract. These data suggest that essential oil VPAEO exerted peripheral analgesic via inhibition of prostaglandin synthesis. PMID:21046983

  13. Multi-species occurrence models to evaluate the effects of conservation and management actions

    USGS Publications Warehouse

    Zipkin, E.F.; Andrew, Royle J.; Dawson, D.K.; Bates, S.

    2010-01-01

    Conservation and management actions often have direct and indirect effects on a wide range of species. As such, it is important to evaluate the impacts that such actions may have on both target and non-target species within a region. Understanding how species richness and composition differ as a result of management treatments can help determine potential ecological consequences. Yet it is difficult to estimate richness because traditional sampling approaches detect species at variable rates and some species are never observed. We present a framework for assessing management actions on biodiversity using a multi-species hierarchical model that estimates individual species occurrences, while accounting for imperfect detection of species. Our model incorporates species-specific responses to management treatments and local vegetation characteristics and a hierarchical component that links species at a community-level. This allows for comprehensive inferences on the whole community or on assemblages of interest. Compared to traditional species models, occurrence estimates are improved for all species, even for those that are rarely observed, resulting in more precise estimates of species richness (including species that were unobserved during sampling). We demonstrate the utility of this approach for conservation through an analysis comparing bird communities in two geographically similar study areas: one in which white-tailed deer (Odocoileus virginianus) densities have been regulated through hunting and one in which deer densities have gone unregulated. Although our results indicate that species and assemblage richness were similar in the two study areas, point-level richness was significantly influenced by local vegetation characteristics, a result that would have been underestimated had we not accounted for variability in species detection.

  14. ARSENIC MODE OF ACTION AND DEVELOPING A BBDR MODEL

    EPA Science Inventory

    The current USEPA cancer risk assessment for inorganic arsenic is based on a linear extrapolation of the epidemiological data from exposed populations in Taiwan. However, proposed key events in the mode of action (MoA) for arsenic-induced cancer (which may include altered DNA me...

  15. Action perception predicts action performance

    PubMed Central

    Bailey, Heather R.; Kurby, Christopher A.; Giovannetti, Tania; Zacks, Jeffrey M.

    2013-01-01

    Everyday action impairments often are observed in demented older adults, and they are common potential barriers to functional independence. We evaluated whether the ability to segment and efficiently encode activities is related to the ability to execute activities. Further, we evaluated whether brain regions important for segmentation also were important for action performance. Cognitively healthy older adults and those with very mild or mild dementia of the Alzheimer's type watched and segmented movies of everyday activities and then completed the Naturalistic Action Test. Structural MRI was used to measure volume in the dorsolateral prefrontal cortex (DLPFC), medial temporal lobes (MTL), posterior cortex, and anterior cingulate cortex (ACC). Dementia status and the ability to segment everyday activities strongly predicted naturalistic action performance, and MTL volume largely accounted for this relationship. In addition, the current results supported the Omission-Commission Model: Different cognitive and neurological mechanisms predicted different types of action error. Segmentation, dementia severity, and MTL volume predicted everyday omission errors, DLPFC volume predicted commission errors, and ACC volume predicted action additions. These findings suggest that event segmentation may be critical for effective action production, and that the segmentation and production of activities may recruit the same event representation system. PMID:23851113

  16. Evaluating potential changes in salmonid rearing capacity from alternative sets of rehabilitation actions in the Trinity River, California

    NASA Astrophysics Data System (ADS)

    Beechie, T. J.; Pess, G. R.; Imaki, H.; Martin, A.; Alvarez, J.; Goodman, D.

    2013-12-01

    River restoration plans often propose numerous rehabilitation actions to address key habitat impairments for salmonids. However, restoration plans rarely propose alternative sets of actions or attempt to quantify the potential benefits to targeted biota. In this paper we use geomorphic and biological analyses to estimate restoration potential for each of 37 reaches in a 64-km section of Trinity River, California from the North Fork Trinity River to Lewiston Dam (the focus of habitat rehabilitation efforts under the Trinity River Restoration Program). We first predicted the channel pattern that might develop based in each reach on slope-discharge criteria, and then used these potential patterns along with floodplain width to estimate the maximum sinuosity that restoration actions could likely achieve, as well as a maximum side-channel length that might be created in each reach. For each scenario, we then used existing stream habitat and juvenile salmonid data from previous studies in the Trinity River and other watersheds to determine current and restored carrying capacity. Potential increases in Chinook and steelhead carrying capacity range from 39% for a relatively realistic estimate of increasing habitat quality (more low velocity areas with cover) to 67% for a more optimistic scenario that increases both sinuosity and habitat quality. Only the most optimistic scenario that increases habitat quality, increases sinuosity, and constructs tens of kilometers of side channels more than doubles potential juvenile salmonid production (140% increase). These quantitative predictions provide a frame of reference for evaluating alternative restoration options, and for setting measurable restoration goals.

  17. Optogenetics-enabled dynamic modulation of action potential duration in atrial tissue: feasibility of a novel therapeutic approach

    PubMed Central

    Karathanos, Thomas V.; Boyle, Patrick M.; Trayanova, Natalia A.

    2014-01-01

    Aims Diseases that abbreviate the cardiac action potential (AP) by increasing the strength of repolarizing transmembrane currents are highly arrhythmogenic. It has been proposed that optogenetic tools could be used to restore normal AP duration (APD) in the heart under such disease conditions. This study aims to evaluate the efficacy of an optogenetic treatment modality for prolonging pathologically shortened APs in a detailed computational model of short QT syndrome (SQTS) in the human atria, and compare it to drug treatment. Methods and results We used a human atrial myocyte model with faster repolarization caused by SQTS; light sensitivity was inscribed via the presence of channelrhodopsin-2 (ChR2). We conducted simulations in single cells and in a magnetic resonance imaging-based model of the human left atrium (LA). Application of an appropriate optical stimulus to a diseased cell dynamically increased APD, producing an excellent match to control AP (<1.5 mV deviation); treatment of a diseased cell with an AP-prolonging drug (chloroquine) also increased APD, but the match to control AP was worse (>5 mV deviation). Under idealized conditions in the LA (uniform ChR2-expressing cell distribution, no light attenuation), optogenetics-based therapy outperformed chloroquine treatment (APD increased to 87% and 81% of control). However, when non-uniform ChR2-expressing cell distribution and light attenuation were incorporated, optogenetics-based treatment was less effective (APD only increased to 55%). Conclusion This study demonstrates proof of concept for optogenetics-based treatment of diseases that alter atrial AP shape. We identified key practical obstacles intrinsic to the optogenetic approach that must be overcome before such treatments can be realized. PMID:25362173

  18. Activity-dependent synaptic GRIP1 accumulation drives synaptic scaling up in response to action potential blockade

    PubMed Central

    Gainey, Melanie A.; Tatavarty, Vedakumar; Nahmani, Marc; Lin, Heather; Turrigiano, Gina G.

    2015-01-01

    Synaptic scaling is a form of homeostatic plasticity that stabilizes neuronal firing in response to changes in synapse number and strength. Scaling up in response to action-potential blockade is accomplished through increased synaptic accumulation of GluA2-containing AMPA receptors (AMPAR), but the receptor trafficking steps that drive this process remain largely obscure. Here, we show that the AMPAR-binding protein glutamate receptor-interacting protein-1 (GRIP1) is essential for regulated synaptic AMPAR accumulation during scaling up. Synaptic abundance of GRIP1 was enhanced by activity deprivation, directly increasing synaptic GRIP1 abundance through overexpression increased the amplitude of AMPA miniature excitatory postsynaptic currents (mEPSCs), and shRNA-mediated GRIP1 knockdown prevented scaling up of AMPA mEPSCs. Furthermore, knockdown and replace experiments targeting either GRIP1 or GluA2 revealed that scaling up requires the interaction between GRIP1 and GluA2. Finally, GRIP1 synaptic accumulation during scaling up did not require GluA2 binding. Taken together, our data support a model in which activity-dependent trafficking of GRIP1 to synaptic sites drives the forward trafficking and enhanced synaptic accumulation of GluA2-containing AMPAR during synaptic scaling up. PMID:26109571

  19. Copper(II)-Bis(Thiosemicarbazonato) Complexes as Antibacterial Agents: Insights into Their Mode of Action and Potential as Therapeutics

    PubMed Central

    Goytia, Maira M.; Donnelly, Paul S.; Schembri, Mark A.; Shafer, William M.

    2015-01-01

    There is increasing interest in the use of lipophilic copper (Cu)-containing complexes to combat bacterial infections. In this work, we showed that Cu complexes with bis(thiosemicarbazone) ligands [Cu(btsc)] exert antibacterial activity against a range of medically significant pathogens. Previous work using Neisseria gonorrhoeae showed that Cu(btsc) complexes may act as inhibitors of respiratory dehydrogenases in the electron transport chain. We now show that these complexes are also toxic against pathogens that lack a respiratory chain. Respiration in Escherichia coli was slightly affected by Cu(btsc) complexes, but our results indicate that, in this model bacterium, the complexes act primarily as agents that deliver toxic Cu ions efficiently into the cytoplasm. Although the chemistry of Cu(btsc) complexes may dictate their mechanism of action, their efficacy depends heavily on bacterial physiology. This is linked to the ability of the target bacterium to tolerate Cu and, additionally, the susceptibility of the respiratory chain to direct inhibition by Cu(btsc) complexes. The physiology of N. gonorrhoeae, including multidrug-resistant strains, makes it highly susceptible to damage by Cu ions and Cu(btsc) complexes, highlighting the potential of Cu(btsc) complexes (and Cu-based therapeutics) as a promising treatment against this important bacterial pathogen. PMID:26239980

  20. Toward panoramic in situ mapping of action potential propagation in transgenic hearts to investigate initiation and therapeutic control of arrhythmias

    PubMed Central

    Dura, Miroslav; Schröder-Schetelig, Johannes; Luther, Stefan; Lehnart, Stephan E.

    2014-01-01

    To investigate the dynamics and propensity for arrhythmias in intact transgenic hearts comprehensively, optical strategies for panoramic fluorescence imaging of action potential (AP) propagation are essential. In particular, mechanism-oriented molecular studies usually depend on transgenic mouse hearts of only a few millimeters in size. Furthermore, the temporal scales of the mouse heart remain a challenge for panoramic fluorescence imaging with heart rates ranging from 200 min−1 (e.g., depressed sinus node function) to over 1200 min−1 during fast arrhythmias. To meet these challenging demands, we and others developed physiologically relevant mouse models and characterized their hearts with planar AP mapping. Here, we summarize the progress toward panoramic fluorescence imaging and its prospects for the mouse heart. In general, several high-resolution cameras are synchronized and geometrically arranged for panoramic voltage mapping and the surface and blood vessel anatomy documented through image segmentation and heart surface reconstruction. We expect that panoramic voltage imaging will lead to novel insights about molecular arrhythmia mechanisms through quantitative strategies and organ-representative analysis of intact mouse hearts. PMID:25249982

  1. Transplantation of Glial Cells Enhances Action Potential Conduction of Amyelinated Spinal Cord Axons in the Myelin-Deficient Rat

    NASA Astrophysics Data System (ADS)

    Utzschneider, David A.; Archer, David R.; Kocsis, Jeffery D.; Waxman, Stephen G.; Duncan, Ian D.

    1994-01-01

    A central issue in transplantation research is to determine how and when transplantation of neural tissue can influence the development and function of the mammalian central nervous system. Of particular interest is whether electrophysiological function in the traumatized or diseased mammalian central nervous system can be improved by the replacement of cellular elements that are missing or damaged. Although it is known that transplantation of neural tissue can lead to functional improvement in models of neurological disease characterized by neuronal loss, less is known about results of transplantation in disorders of myelin. We report here that transplantation of glial cells into the dorsal columns of neonatal myelin-deficient rat spinal cords leads to myelination and a 3-fold increase in conduction velocity. We also show that impulses can propagate into and out of the transplant region and that axons myelinated by transplanted cells do not have impaired frequency-response properties. These results demonstrate that myelination following central nervous system glial cell transplantation enhances action potential conduction in myelin-deficient axons, with conduction velocity approaching normal values.

  2. Copper(II)-Bis(Thiosemicarbazonato) Complexes as Antibacterial Agents: Insights into Their Mode of Action and Potential as Therapeutics.

    PubMed

    Djoko, Karrera Y; Goytia, Maira M; Donnelly, Paul S; Schembri, Mark A; Shafer, William M; McEwan, Alastair G

    2015-10-01

    There is increasing interest in the use of lipophilic copper (Cu)-containing complexes to combat bacterial infections. In this work, we showed that Cu complexes with bis(thiosemicarbazone) ligands [Cu(btsc)] exert antibacterial activity against a range of medically significant pathogens. Previous work using Neisseria gonorrhoeae showed that Cu(btsc) complexes may act as inhibitors of respiratory dehydrogenases in the electron transport chain. We now show that these complexes are also toxic against pathogens that lack a respiratory chain. Respiration in Escherichia coli was slightly affected by Cu(btsc) complexes, but our results indicate that, in this model bacterium, the complexes act primarily as agents that deliver toxic Cu ions efficiently into the cytoplasm. Although the chemistry of Cu(btsc) complexes may dictate their mechanism of action, their efficacy depends heavily on bacterial physiology. This is linked to the ability of the target bacterium to tolerate Cu and, additionally, the susceptibility of the respiratory chain to direct inhibition by Cu(btsc) complexes. The physiology of N. gonorrhoeae, including multidrug-resistant strains, makes it highly susceptible to damage by Cu ions and Cu(btsc) complexes, highlighting the potential of Cu(btsc) complexes (and Cu-based therapeutics) as a promising treatment against this important bacterial pathogen. PMID:26239980

  3. Propagation of the change in the membrane potential using a biocell-model.

    PubMed

    Takano, Yoshinari; Shirai, Osamu; Kitazumi, Yuki; Kano, Kenji

    2016-05-14

    A new model system of nerve conduction, which has two sites (the potential-sending and the potential-receiving sites) was constructed by the use of some liquid-membrane cells which mimic the function of the K(+) and Na(+) channels. The model system setup was such that the membrane potential of the K(+)-channel cell (resting potential) was different from that of the Na(+)-channel cell (action potential). Initially, the K(+)-channel cell at the potential-sending site was connected to that at the potential-receiving site. After switching from the K(+)-channel cell to the Na(+)-channel cell at the potential-sending site, the membrane potential of the K(+)-channel cell at the potential-receiving site began to vary with the generation of the circulating current. By placing several K(+)-channel cells in parallel at the potential-receiving site, the propagation mechanism of the action potential was interpreted and the influence of the resistor and the capacitor on the propagation was evaluated. PMID:27094735

  4. Modeling International Space Station (ISS) Floating Potentials

    NASA Technical Reports Server (NTRS)

    Ferguson, Dale C.; Gardner, Barbara

    2002-01-01

    The floating potential of the International Space Station (ISS) as a function of the electron current collection of its high voltage solar array panels is derived analytically. Based on Floating Potential Probe (FPP) measurements of the ISS potential and ambient plasma characteristics, it is shown that the ISS floating potential is a strong function of the electron temperature of the surrounding plasma. While the ISS floating potential has so far not attained the pre-flight predicted highly negative values, it is shown that for future mission builds, ISS must continue to provide two-fault tolerant arc-hazard protection for astronauts on EVA.

  5. Early Afterdepolarizations with Growing Amplitudes via Delayed Subcritical Hopf Bifurcations and Unstable Manifolds of Saddle Foci in Cardiac Action Potential Dynamics

    PubMed Central

    Kügler, Philipp

    2016-01-01

    Early afterdepolarizations (EADs) are pathological oscillations in cardiac action potentials during the repolarization phase and may be caused by drug side effects, ion channel disease or oxidative stress. The most widely observed EAD pattern is characterized by oscillations with growing amplitudes. So far, its occurence has been explained in terms of a supercritical Hopf bifurcation in the fast subsystem of the action potential dynamics from which stable limit cycles with growing amplitudes emerge. The novel contribution of this article is the introduction of two alternative explanations of EAD genesis with growing amplitudes that do not involve stable limit cycles in fast subsystems. In particular, we demonstrate that EAD patterns with growing amplitudes may alternatively arise due to a delayed subcritical Hopf bifurcation or an unstable manifold of a saddle focus fixed point in the full fast-slow system modelling the action potential. Our work extends the list of possible dynamical EAD mechanisms and may contribute to a classification of drug effects in preclinical cardiotoxicity testing. PMID:26977805

  6. On-line and Model-based Approaches to the Visual Control of Action

    PubMed Central

    Zhao, Huaiyong; Warren, William H.

    2014-01-01

    Two general approaches to the visual control of action have emerged in last few decades, known as the on-line and model-based approaches. The key difference between them is whether action is controlled by current visual information or on the basis of an internal world model. In this paper, we evaluate three hypotheses: strong on-line control, strong model-based control, and a hybrid solution that combines on-line control with weak off-line strategies. We review experimental research on the control of locomotion and manual actions, which indicates that (a) an internal world model is neither sufficient nor necessary to control action at normal levels of performance; (b) current visual information is necessary and sufficient to control action at normal levels; and (c) under certain conditions (e.g. occlusion) action is controlled by less accurate, simple strategies such as heuristics, visual-motor mappings, or spatial memory. We conclude that the strong model-based hypothesis is not sustainable. Action is normally controlled on-line when current information is available, consistent with the strong on-line control hypothesis. In exceptional circumstances, action is controlled by weak, context-specific, off-line strategies. This hybrid solution is comprehensive, parsimonious, and able to account for a variety of tasks under a range of visual conditions. PMID:25454700

  7. Mode of action of Bacillus thuringiensis Cry and Cyt toxins and their potential for insect control.

    PubMed

    Bravo, Alejandra; Gill, Sarjeet S; Soberón, Mario

    2007-03-15

    Bacillus thuringiensis Crystal (Cry) and Cytolitic (Cyt) protein families are a diverse group of proteins with activity against insects of different orders--Lepidoptera, Coleoptera, Diptera and also against other invertebrates such as nematodes. Their primary action is to lyse midgut epithelial cells by inserting into the target membrane and forming pores. Among this group of proteins, members of the 3-Domain Cry family are used worldwide for insect control, and their mode of action has been characterized in some detail. Phylogenetic analyses established that the diversity of the 3-Domain Cry family evolved by the independent evolution of the three domains and by swapping of domain III among toxins. Like other pore-forming toxins (PFT) that affect mammals, Cry toxins interact with specific receptors located on the host cell surface and are activated by host proteases following receptor binding resulting in the formation of a pre-pore oligomeric structure that is insertion competent. In contrast, Cyt toxins directly interact with membrane lipids and insert into the membrane. Recent evidence suggests that Cyt synergize or overcome resistance to mosquitocidal-Cry proteins by functioning as a Cry-membrane bound receptor. In this review we summarize recent findings on the mode of action of Cry and Cyt toxins, and compare them to the mode of action of other bacterial PFT. Also, we discuss their use in the control of agricultural insect pests and insect vectors of human diseases. PMID:17198720

  8. Preparing Social Justice Oriented Teachers: The Potential Role of Action Research in the PDS

    ERIC Educational Resources Information Center

    Dodman, Stephanie L.; Lai, Kerri; Campet, Melissa; Cavallero-Lotocki, Renee; Hopkins, Aaron; Onidi, Christine

    2014-01-01

    Deliberate investigation into practice is an essential of the National Association for Professional Development Schools' defining elements of a Professional Development School (PDS). This article reports on the pilot efforts of one PDS as it initiated deliberate investigation through action research with a small group of teacher candidates.…

  9. The Potential of General Classroom Observation: Turkish EFL Teachers' Perceptions, Sentiments, and Readiness for Action

    ERIC Educational Resources Information Center

    Merç, Ali

    2015-01-01

    The purpose of this study was to determine Turkish EFL teachers' attitudes towards classroom observation. 204 teachers from different school settings responded to an online questionnaire. Data were analyzed according to three types of attitudes towards classroom observation: perceptions, sentiments, and readiness for action. The findings revealed…

  10. Action Potential-Evoked Calcium Release Is Impaired in Single Skeletal Muscle Fibers from Heart Failure Patients

    PubMed Central

    DiFranco, Marino; Quiñonez, Marbella; Shieh, Perry; Fonarow, Gregg C.; Cruz, Daniel; Deng, Mario C.; Vergara, Julio L.; Middlekauff, Holly R.

    2014-01-01

    Background Exercise intolerance in chronic heart failure (HF) has been attributed to abnormalities of the skeletal muscles. Muscle function depends on intact excitation-contraction coupling (ECC), but ECC studies in HF models have been inconclusive, due to deficiencies in the animal models and tools used to measure calcium (Ca2+) release, mandating investigations in skeletal muscle from HF patients. The purpose of this study was to test the hypothesis that Ca2+ release is significantly impaired in the skeletal muscle of HF patients in whom exercise capacity is severely diminished compared to age-matched healthy volunteers. Methods and Findings Using state-of-the-art electrophysiological and optical techniques in single muscle fibers from biopsies of the locomotive vastus lateralis muscle, we measured the action potential (AP)-evoked Ca2+ release in 4 HF patients and 4 age-matched healthy controls. The mean peak Ca2+ release flux in fibers obtained from HF patients (10±1.2 µM/ms) was markedly (2.6-fold) and significantly (p<0.05) smaller than in fibers from healthy volunteers (28±3.3 µM/ms). This impairment in AP-evoked Ca2+ release was ubiquitous and was not explained by differences in the excitability mechanisms since single APs were indistinguishable between HF patients and healthy volunteers. Conclusions These findings prove the feasibility of performing electrophysiological experiments in single fibers from human skeletal muscle, and offer a new approach for investigations of myopathies due to HF and other diseases. Importantly, we have demonstrated that one step in the ECC process, AP-evoked Ca2+ release, is impaired in single muscle fibers in HF patients. PMID:25310188

  11. DESCRIPTION OF MODELING ANALYSES IN SUPPORT OF THE 200-ZP-1 REMEDIAL DESIGN/REMEDIAL ACTION

    SciTech Connect

    VONGARGEN BH

    2009-11-03

    The Feasibility Study/or the 200-ZP-1 Groundwater Operable Unit (DOE/RL-2007-28) and the Proposed Plan/or Remediation of the 200-ZP-1 Groundwater Operable Unit (DOE/RL-2007-33) describe the use of groundwater pump-and-treat technology for the 200-ZP-1 Groundwater Operable Unit (OU) as part of an expanded groundwater remedy. During fiscal year 2008 (FY08), a groundwater flow and contaminant transport (flow and transport) model was developed to support remedy design decisions at the 200-ZP-1 OU. This model was developed because the size and influence of the proposed 200-ZP-1 groundwater pump-and-treat remedy will have a larger areal extent than the current interim remedy, and modeling is required to provide estimates of influent concentrations and contaminant mass removal rates to support the design of the aboveground treatment train. The 200 West Area Pre-Conceptual Design/or Final Extraction/Injection Well Network: Modeling Analyses (DOE/RL-2008-56) documents the development of the first version of the MODFLOW/MT3DMS model of the Hanford Site's Central Plateau, as well as the initial application of that model to simulate a potential well field for the 200-ZP-1 remedy (considering only the contaminants carbon tetrachloride and technetium-99). This document focuses on the use of the flow and transport model to identify suitable extraction and injection well locations as part of the 200 West Area 200-ZP-1 Pump-and-Treat Remedial Design/Remedial Action Work Plan (DOEIRL-2008-78). Currently, the model has been developed to the extent necessary to provide approximate results and to lay a foundation for the design basis concentrations that are required in support of the remedial design/remediation action (RD/RA) work plan. The discussion in this document includes the following: (1) Assignment of flow and transport parameters for the model; (2) Definition of initial conditions for the transport model for each simulated contaminant of concern (COC) (i.e., carbon

  12. Proposed actions are no actions: re-modeling an ontology design pattern with a realist top-level ontology

    PubMed Central

    2012-01-01

    Background Ontology Design Patterns (ODPs) are representational artifacts devised to offer solutions for recurring ontology design problems. They promise to enhance the ontology building process in terms of flexibility, re-usability and expansion, and to make the result of ontology engineering more predictable. In this paper, we analyze ODP repositories and investigate their relation with upper-level ontologies. In particular, we compare the BioTop upper ontology to the Action ODP from the NeOn an ODP repository. In view of the differences in the respective approaches, we investigate whether the Action ODP can be embedded into BioTop. We demonstrate that this requires re-interpreting the meaning of classes of the NeOn Action ODP in the light of the precepts of realist ontologies. Results As a result, the re-design required clarifying the ontological commitment of the ODP classes by assigning them to top-level categories. Thus, ambiguous definitions are avoided. Classes of real entities are clearly distinguished from classes of information artifacts. The proposed approach avoids the commitment to the existence of unclear future entities which underlies the NeOn Action ODP. Our re-design is parsimonious in the sense that existing BioTop content proved to be largely sufficient to define the different types of actions and plans. Conclusions The proposed model demonstrates that an expressive upper-level ontology provides enough resources and expressivity to represent even complex ODPs, here shown with the different flavors of Action as proposed in the NeOn ODP. The advantage of ODP inclusion into a top-level ontology is the given predetermined dependency of each class, an existing backbone structure and well-defined relations. Our comparison shows that the use of some ODPs is more likely to cause problems for ontology developers, rather than to guide them. Besides the structural properties, the explanation of classification results were particularly hard to grasp for

  13. Modeling and analysis of systems using the Least Action Principle in information theory

    NASA Astrophysics Data System (ADS)

    Guldal, Serkan

    The Least Action Principle (LAP) is widely applied to search for solutions to problems of classical mechanics. It claims that if an infinitesimal change does not affect the action of a system, that action would be the least action. In classical mechanics, if a particle moves from point A to point B, it will search for the path that requires the least energy consumption. Modeling physical phenomena utilizing LAP helps to predict an equation of motion and this principle is applicable for all known systems. In this dissertation, we use the maximum independent set from graph theory as a guiding principle to model for least action. It is shown that the maximum independence number will correspond to the least action. We demonstrate the use of the LAP in information theory and its use in the modeling and the analysis of systems. Thus, we will have a general model which is applicable to any known system. We have applied the LAP model to the Conant network decomposition technique. We demonstrated the applicability of our model in our case study that the Conant network decomposition technique computes the least action of the given network of the given data set.

  14. Contribution of BK channels to action potential repolarisation at minimal cytosolic Ca2+ concentration in chromaffin cells.

    PubMed

    Scott, Ricardo S; Bustillo, Diego; Olivos-Oré, Luis Alcides; Cuchillo-Ibañez, Inmaculada; Barahona, Maria Victoria; Carbone, Emilio; Artalejo, Antonio R

    2011-10-01

    BK channels modulate cell firing in excitable cells in a voltage-dependent manner regulated by fluctuations in free cytosolic Ca(2+) during action potentials. Indeed, Ca(2+)-independent BK channel activity has ordinarily been considered not relevant for the physiological behaviour of excitable cells. We employed the patch-clamp technique and selective BK channel blockers to record K(+) currents from bovine chromaffin cells at minimal intracellular (about 10 nM) and extracellular (free Ca(2+)) Ca(2+) concentrations. Despite their low open probability under these conditions (V(50) of +146.8 mV), BK channels were responsible for more than 25% of the total K(+) efflux during the first millisecond of a step depolarisation to +20 mV. Moreover, BK channels activated about 30% faster (τ = 0.55 ms) than the rest of available K(+) channels. The other main source of fast voltage-dependent K(+) efflux at such a low Ca(2+) was a transient K(+) (I(A)-type) current activating with V (50) = -14.2 mV. We also studied the activation of BK currents in response to action potential waveforms and their contribution to shaping action potentials both in the presence and the absence of extracellular Ca(2+). Our results show that BK channels activate during action potentials and accelerate cell repolarisation even at minimal Ca(2+) concentration, and suggest that they could do so also in the presence of extracellular Ca(2+), before Ca(2+) entering the cell facilitates their activity. PMID:21755285

  15. 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.

  16. 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.

  17. A simplified model of collision-driven dynamo action in small bodies

    NASA Astrophysics Data System (ADS)

    Wei, Xing; Arlt, Rainer; Tilgner, Andreas

    2014-06-01

    We investigate numerically the self-sustained dynamo action in a spinning sphere whose sense of rotation reverses periodically. This system serves as a simple model of a dynamo in small bodies powered by frequent collisions. It is found that dynamo action is possible in some intervals of collision rates. At high Ekman numbers the laminar spin-up flow is helical in the boundary layers and the Ekman circulation together with the azimuthal shear powers the dynamo action. At low Ekman number a non-axisymmetric instability helps the dynamo action. The intermittency of magnetic field occurs at low Ekman number.

  18. Effect of depth of general anesthesia on the threshold of electrically evoked compound action potential in cochlear implantation.

    PubMed

    Eftekharian, Ali; Amizadeh, Maryam; Mottaghi, Kamran; Safari, Farhad; Mahani, Mozhgan Hosseinerezai; Ranjbar, Leila Azadeh; Abdi, Ali; Mokari, Nooshin

    2015-10-01

    The purpose of the present study was to evaluate effect of depth of general anesthesia on the threshold of electrically evoked compound action potential in cochlear implantation. A prospective clinical study in a single-subject design was conducted in the cochlear implant center of a tertiary care University-based hospital. Sixty-one cochlear-implanted children with bilateral, severe to profound sensory neural hearing loss were enrolled in the study. During the operation electrically evoked compound action potentials (e-ECAP) were measured in two phase of general anesthesia; in deep and in light anesthesia. Thresholds of e-ECAP in these two phases of anesthesia were compared. Thirty-one children received HiRes90k1j prosthesis and 30 children received CI24RE prosthesis. Thresholds difference of electrically evoked compound action potential between light and deep anesthesia in all tested electrodes in either group were statistically significant (P < 0.001). Non-measurable e-ECAP in some electrodes at deep anesthesia was measurable in light phase of anesthesia. Depth of anesthesia can have significant influence on e-ECAP threshold and it is important to reduce the depth of anesthesia to achieve better results. PMID:25145642

  19. 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

  20. Modeling situated abstraction : action coalescence via multidimensional coherence.

    SciTech Connect

    Sallach, D. L.; Decision and Information Sciences; Univ. of Chicago

    2007-01-01

    Situated social agents weigh dozens of priorities, each with its own complexities. Domains of interest are intertwined, and progress in one area either complements or conflicts with other priorities. Interpretive agents address these complexities through: (1) integrating cognitive complexities through the use of radial concepts, (2) recognizing the role of emotion in prioritizing alternatives and urgencies, (3) using Miller-range constraints to avoid oversimplified notions omniscience, and (4) constraining actions to 'moves' in multiple prototype games. Situated agent orientations are dynamically grounded in pragmatic considerations as well as intertwined with internal and external priorities. HokiPoki is a situated abstraction designed to shape and focus strategic agent orientations. The design integrates four pragmatic pairs: (1) problem and solution, (2) dependence and power, (3) constraint and affordance, and (4) (agent) intent and effect. In this way, agents are empowered to address multiple facets of a situation in an exploratory, or even arbitrary, order. HokiPoki is open to the internal orientation of the agent as it evolves, but also to the communications and actions of other agents.

  1. In the elderly, failure to update internal models leads to over-optimistic predictions about upcoming actions.

    PubMed

    Lafargue, Gilles; Noël, Myriam; Luyat, Marion

    2013-01-01

    Before an action is performed, the brain simulates the body's dynamic behavior in relation to the environment, estimates the possible outcomes and assesses the feasibility of potential actions. Here, we tested a hypothesis whereby age-related changes in sensorimotor abilities result in failure to update internal models of action in the elderly. Young and older adults were required to judge in advance whether or not they could stand on an inclined plane (Experiment 1). Relative to young adults, elderly adults overestimated their postural capabilities: although the two groups made similar feasibility judgments, elderly participants showed significantly worse postural performance levels. This tendency to overestimate their own ability persisted when elderly adults had to not only estimate the feasibility of an action but also endanger themselves by walking towards an obstacle that was too high for them to clear (Experiment 2). An age-related failure to update internal models may prompt the elderly to make over-optimistic predictions about upcoming actions. In turn, this may favor risky motor decision-making and promote falls. PMID:23326312

  2. Diosgenin, 4-hydroxyisoleucine, and fiber from fenugreek: mechanisms of actions and potential effects on metabolic syndrome.

    PubMed

    Fuller, Scott; Stephens, Jacqueline M

    2015-03-01

    Metabolic syndrome and its complications continue to rise in prevalence and show no signs of abating in the immediate future. Therefore, the search for effective treatments is a high priority in biomedical research. Products derived from botanicals have a time-honored history of use in the treatment of metabolic diseases including type 2 diabetes. Trigonella foenum-graecum, commonly known as fenugreek, is an annual herbaceous plant that has been a staple of traditional herbal medicine in many cultures. Although fenugreek has been studied in both clinical and basic research settings, questions remain about its efficacy and biologic mechanisms of action. Diosgenin, 4-hydroxyisoleucine, and the fiber component of the plant are the most intensively studied bioactive constituents present in fenugreek. These compounds have been demonstrated to exert beneficial effects on several physiologic markers including glucose tolerance, inflammation, insulin action, liver function, blood lipids, and cardiovascular health. Although insights into the molecular mechanisms underlying the favorable effects of fenugreek have been gained, we still do not have definitive evidence establishing its role as a therapeutic agent in metabolic disease. This review aims to summarize the currently available evidence on the physiologic effects of the 3 best-characterized bioactive compounds of fenugreek, with particular emphasis on biologic mechanisms of action relevant in the context of metabolic syndrome. PMID:25770257

  3. The Potential of Growth Mixture Modelling

    ERIC Educational Resources Information Center

    Muthen, Bengt

    2006-01-01

    The authors of the paper on growth mixture modelling (GMM) give a description of GMM and related techniques as applied to antisocial behaviour. They bring up the important issue of choice of model within the general framework of mixture modelling, especially the choice between latent class growth analysis (LCGA) techniques developed by Nagin and…

  4. Conceptual models to guide best practices in organization and development of State Action Coalitions.

    PubMed

    Cramer, Mary E; Lazure, Linda; Morris, Kathy J; Valerio, Marilyn; Morris, Rosanna

    2013-01-01

    The RWJF/AARP National Campaign for Action established a goal of establishing Action Coalitions in every state by 2012. Last year, a small Steering Committee formed in Nebraska and used two conceptual models to guide the organization and development of its Action Coalition. The purpose of this article is to present the Internal Coalition Outcome Hierarchy (ICOH) model that guided development of partnership and coalition building. The second model, Determining Program Feasibility, provided a framework for data collection and analysis to identify the opportunities and challenges for strategic program planning to accomplish identified key priorities for Nebraska. A discussion of the models' applications is included and offered as best practices for others seeking to form partnership/coalitions and establish action plans and priorities. PMID:22921306

  5. Action recognition using spatiotemporal features and hybrid generative/discriminative models

    NASA Astrophysics Data System (ADS)

    Liu, Jia; Yang, Jie

    2012-04-01

    We propose a new method for human action recognition based on multiple features and a hybrid generative/discriminative model. Specifically, we propose a new action representation based on computing a rich set of descriptors from Affine-SIFT key point trajectories. A new hybrid generative/discriminative approach based on support vector machine and topic model is proposed using Fisher kernel method for action recognition. Fisher score for the topic model is evaluated by the variational inference algorithm. To obtain efficient and compact representations for actions, we develop a feature fusion method to combine spatial-temporal local motion descriptors and demonstrate how this kernel framework can be used to combine different types of features and models into a single classifier. Our experiments, conducted on a number of popular datasets, show performance improvements over the corresponding generative approach and are competitive with the best results reported in the literature.

  6. PHYSIOLOCIGALLY BASED PHARMACOKINETIC (PBPK) MODELING AND MODE OF ACTION IN DOSE-RESPONSE ASSESSMENT

    EPA Science Inventory

    PHYSIOLOGICALLY BASED PHARMACOKINETIC (PBPK) MODELING AND MODE OF ACTION IN DOSE-RESPONSE ASSESSMENT. Barton HA. Experimental Toxicology Division, National Health and Environmental Effects Laboratory, ORD, U.S. EPA
    Dose-response analysis requires quantitatively linking infor...

  7. RECENT ENHANCEMENTS TO THE DIETARY EXPOSURE POTENTIAL MODEL

    EPA Science Inventory

    Presentation describes recent enhancements & new applications of the Dietary Exposure Potential Model (DEPM), a model developed to assist in design & interpretation of dietary exposure measurements. Model is an interactive system that provides dietary exposure estimates using dat...

  8. Action Potential Energetics at the Organismal Level Reveal a Trade-Off in Efficiency at High Firing Rates

    PubMed Central

    Gilmour, Kathleen M.; Moorhead, Mayron J.; Perry, Steve F.; Markham, Michael R.

    2014-01-01

    The energetic costs of action potential (AP) production constrain the evolution of neural codes and brain networks. Cellular-level estimates of AP-related costs are typically based on voltage-dependent Na+ currents that drive active transport by the Na+/K+ ATPase to maintain the Na+ and K+ ion concentration gradients necessary for AP production. However, these estimates of AP cost have not been verified at the organismal level. Electric signaling in the weakly electric fish Eigenmannia virescens requires that specialized cells in an electric organ generate APs with large Na+ currents at high rates (200–600 Hz). We measured these currents using a voltage-clamp protocol and then estimated the energetic cost at the cellular level using standard methods. We then used this energy-intensive signaling behavior to measure changes in whole-animal energetics for small changes in electric discharge rate. At low rates, the whole-animal measure of AP cost was similar to our cellular-level estimates. However, AP cost increased nonlinearly with increasing firing rates. We show, with a biophysical model, that this nonlinearity can arise from the increasing cost of maintaining AP amplitude at high rates. Our results confirm that estimates of energetic costs based on Na+ influx are appropriate for low baseline firing rates, but that extrapolating to high firing rates may underestimate true costs in cases in which AP amplitude does not decrease. Moreover, the trade-off between energetic cost and firing rate suggests an additional constraint on the evolution of high-frequency signaling in neuronal systems. PMID:24381281

  9. Evaluation of nystatin containing chitosan hydrogels as potential dual action bio-active restorative materials: in vitro approach.

    PubMed

    Perchyonok, V Tamara; Reher, Vanessa; Zhang, Shengmiao; Basson, Nicki; Grobler, Sias

    2014-01-01

    Healing is a specific biological process related to the general phenomenon of growth and tissue regeneration and is a process generally affected by several systemic conditions or as detrimental side-effects of chemotherapy- and radiotherapy-induced inflammation of the oral mucosa. The objectives of this study is to evaluate the novel chitosan based functional drug delivery systems, which can be successfully incorporated into "dual action bioactive restorative materials", capable of inducing in vitro improved wound healing prototype and containing an antibiotic, such as nystatin, krill oil as an antioxidant and hydroxyapatite as a molecular bone scaffold, which is naturally present in bone and is reported to be successfully used in promoting bone integration when implanted as well as promoting healing. The hydrogels were prepared using a protocol as previously reported by us. The physico-chemical features, including surface morphology (SEM), release behaviors, stability of the therapeutic agent-antioxidant-chitosan, were measured and compared to the earlier reported chitosan-antioxidant containing hydrogels. Structural investigations of the reactive surface of the hydrogel are reported. Release of nystatin was investigated for all newly prepared hydrogels. Bio-adhesive studies were performed in order to assess the suitability of these designer materials. Free radical defense capacity of the biomaterials was evaluated using established in vitro model. The bio-adhesive capacity of the materials in the in vitro system was tested and quantified. It was found that the favorable synergistic effect of free radical built-in defense mechanism of the new functional materials increased sustainable bio-adhesion and therefore acted as a functional multi-dimensional restorative material with potential application in wound healing in vitro. PMID:25459982

  10. Evaluation of Nystatin Containing Chitosan Hydrogels as Potential Dual Action Bio-Active Restorative Materials: in Vitro Approach

    PubMed Central

    Perchyonok, V. Tamara; Reher, Vanessa; Zhang, Shengmiao; Basson, Nicki; Grobler, Sias

    2014-01-01

    Healing is a specific biological process related to the general phenomenon of growth and tissue regeneration and is a process generally affected by several systemic conditions or as detrimental side-effects of chemotherapy- and radiotherapy-induced inflammation of the oral mucosa. The objectives of this study is to evaluate the novel chitosan based functional drug delivery systems, which can be successfully incorporated into “dual action bioactive restorative materials”, capable of inducing in vitro improved wound healing prototype and containing an antibiotic, such as nystatin, krill oil as an antioxidant and hydroxyapatite as a molecular bone scaffold, which is naturally present in bone and is reported to be successfully used in promoting bone integration when implanted as well as promoting healing. The hydrogels were prepared using a protocol as previously reported by us. The physico-chemical features, including surface morphology (SEM), release behaviors, stability of the therapeutic agent-antioxidant-chitosan, were measured and compared to the earlier reported chitosan-antioxidant containing hydrogels. Structural investigations of the reactive surface of the hydrogel are reported. Release of nystatin was investigated for all newly prepared hydrogels. Bio-adhesive studies were performed in order to assess the suitability of these designer materials. Free radical defense capacity of the biomaterials was evaluated using established in vitro model. The bio-adhesive capacity of the materials in the in vitro system was tested and quantified. It was found that the favorable synergistic effect of free radical built-in defense mechanism of the new functional materials increased sustainable bio-adhesion and therefore acted as a functional multi-dimensional restorative material with potential application in wound healing in vitro. PMID:25459982

  11. Effect of activation sequence on transmural patterns of repolarization and action potential duration in rabbit ventricular myocardium

    PubMed Central

    Myles, Rachel C.; Bernus, Olivier; Burton, Francis L.; Cobbe, Stuart M.

    2010-01-01

    Although transmural heterogeneity of action potential duration (APD) is established in single cells isolated from different tissue layers, the extent to which it produces transmural gradients of repolarization in electrotonically coupled ventricular myocardium remains controversial. The purpose of this study was to examine the relative contribution of intrinsic cellular gradients of APD and electrotonic influences to transmural repolarization in rabbit ventricular myocardium. Transmural optical mapping was performed in left ventricular wedge preparations from eight rabbits. Transmural patterns of activation, repolarization, and APD were recorded during endocardial and epicardial stimulation. Experimental results were compared with modeled data during variations in electrotonic coupling. A transmural gradient of APD was evident during endocardial stimulation, which reflected differences previously seen in isolated cells, with the longest APD at the endocardium and the shortest at the epicardium (endo: 165 ± 5 vs. epi: 147 ± 4 ms; P < 0.05). During epicardial stimulation, this gradient reversed (epi: 162 ± 4 vs. endo: 148 ± 6 ms; P < 0.05). In both activation sequences, transmural repolarization followed activation and APD shortened along the activation path such that significant transmural gradients of repolarization did not occur. This correlation between transmural activation time and APD was recapitulated in simulations and varied with changes in intercellular coupling, confirming that it is mediated by electrotonic current flow between cells. These data suggest that electrotonic influences are important in determining the transmural repolarization sequence in rabbit ventricular myocardium and that they are sufficient to overcome intrinsic differences in the electrophysiological properties of the cells across the ventricular wall. PMID:20889843

  12. Potential of rapid adjustment of brief interceptive action using predicted information.

    PubMed

    Ikudome, Sachi; Nakamoto, Hiroki; Yotani, Kengo; Unenaka, Satoshi; Mori, Shiro

    2015-07-01

    Interceptive actions, such as hitting a ball in baseball or tennis, feature a moving target whose parameters (i.e., velocity or trajectory) differ across trials. This means that players are required to make rapid trial-by-trial adjustments. The purpose of this study was to determine whether a brief interceptive action could be adjusted using predicted sensory consequence of movement (pSCM) information, even under severe time constraints where the participants could not adjust their movement using only visual feedback. Participants performed an interceptive action for targets with two different velocities with different occurrence probabilities (20%, 50%, and 80%). Prior to movement onset, we applied transcranial magnetic stimulation (TMS) to the supplementary motor area (SMA), as TMS of the SMA is known to disrupt pSCM activity. We hypothesized that if pSCM information were used to adjust the motor parameters of a brief interception, then TMS would significantly increase the constant temporal error (i.e., the difference between the sum of reaction time and movement time and the total target visible time) for a target velocity with a low probability (20%). This hypothesis is based on the previous findings that the pSCM plays an important role in the adjustment of relatively brief interception. We found that while interceptions that lasted about 250 ms after movement onset were unaffected, interceptions that lasted about 350 ms after movement onset could be influenced by TMS. However, TMS interfered with performance provided that the delivery of the pulse occurred 100 ms before movement onset. This finding suggests that pSCM information that is used for a rapid adjustment is generated only in that specific time interval. PMID:26010202

  13. Model-based action planning involves cortico-cerebellar and basal ganglia networks.

    PubMed

    Fermin, Alan S R; Yoshida, Takehiko; Yoshimoto, Junichiro; Ito, Makoto; Tanaka, Saori C; Doya, Kenji

    2016-01-01

    Humans can select actions by learning, planning, or retrieving motor memories. Reinforcement Learning (RL) associates these processes with three major classes of strategies for action selection: exploratory RL learns state-action values by exploration, model-based RL uses internal models to simulate future states reached by hypothetical actions, and motor-memory RL selects past successful state-action mapping. In order to investigate the neural substrates that implement these strategies, we conducted a functional magnetic resonance imaging (fMRI) experiment while humans performed a sequential action selection task under conditions that promoted the use of a specific RL strategy. The ventromedial prefrontal cortex and ventral striatum increased activity in the exploratory condition; the dorsolateral prefrontal cortex, dorsomedial striatum, and lateral cerebellum in the model-based condition; and the supplementary motor area, putamen, and anterior cerebellum in the motor-memory condition. These findings suggest that a distinct prefrontal-basal ganglia and cerebellar network implements the model-based RL action selection strategy. PMID:27539554

  14. Model-based action planning involves cortico-cerebellar and basal ganglia networks

    PubMed Central

    Fermin, Alan S. R.; Yoshida, Takehiko; Yoshimoto, Junichiro; Ito, Makoto; Tanaka, Saori C.; Doya, Kenji

    2016-01-01

    Humans can select actions by learning, planning, or retrieving motor memories. Reinforcement Learning (RL) associates these processes with three major classes of strategies for action selection: exploratory RL learns state-action values by exploration, model-based RL uses internal models to simulate future states reached by hypothetical actions, and motor-memory RL selects past successful state-action mapping. In order to investigate the neural substrates that implement these strategies, we conducted a functional magnetic resonance imaging (fMRI) experiment while humans performed a sequential action selection task under conditions that promoted the use of a specific RL strategy. The ventromedial prefrontal cortex and ventral striatum increased activity in the exploratory condition; the dorsolateral prefrontal cortex, dorsomedial striatum, and lateral cerebellum in the model-based condition; and the supplementary motor area, putamen, and anterior cerebellum in the motor-memory condition. These findings suggest that a distinct prefrontal-basal ganglia and cerebellar network implements the model-based RL action selection strategy. PMID:27539554

  15. Conservation laws of wave action and potential enstrophy for Rossby waves in a stratified atmosphere

    NASA Technical Reports Server (NTRS)

    Straus, D. M.

    1983-01-01

    The evolution of wave energy, enstrophy, and wave motion for atmospheric Rossby waves in a variable mean flow are discussed from a theoretical and pedagogic standpoint. In the absence of mean flow gradients, the wave energy density satisfies a local conservation law, with the appropriate flow velocity being the group velocity. In the presence of mean flow variations, wave energy is not conserved, but wave action is, provided the mean flow is independent of longitude. Wave enstrophy is conserved for arbitrary variations of the mean flow. Connections with Eiiassen-Palm flux are also discussed.

  16. Conservation laws of wave action and potential enstrophy for Rossby waves in a stratified atmosphere

    NASA Technical Reports Server (NTRS)

    Straus, D. M.

    1983-01-01

    The evolution of wave energy, enstrophy, and wave motion for atmospheric Rossby waves in a variable mean flow are discussed from a theoretical and pedagogic standpoint. In the absence of mean flow gradients, the wave energy density satisfies a local conservation law, with the appropriate flow velocity being the group velocity. In the presence of mean flow variations, wave energy is not conserved, but wave action is, provided the mean flow is independent of longitude. Wave enstrophy is conserved for arbitrary variations of the mean flow. Connections with Eliassen-Palm flux are also discussed.

  17. A value-based practice model of rehabilitation: consumers' recommendations in action.

    PubMed

    Yoshida, Karen K; Self, Hazel M; Renwick, Rebecca M; Forma, Laura L; King, Audrey J; Fell, Leslie A

    2015-01-01

    The purpose of this paper is to present a model of rehabilitation practice that is based on the recommendations of consumers who used rehabilitation services and have a life-changing physical impairment (spinal cord injury - SCI). This value-based practice model is based on two qualitative studies. The first study developed the framework (social adaptation) for a new practice model based on values. The second study, described in this paper, used the framework to learn about recommendations for change in the rehabilitation process. Participants in the second study were 80 volunteers who live with a SCI in the community, across the province of Ontario, Canada. A snowball strategy was used to recruit interested participants. Participants were involved in face-to-face interviews which included questions on what helped and hindered their initial rehabilitation process, and their recommendations for change. In this paper, we described a model that demonstrates how consumer input is essential in shaping a comprehensive rehabilitation process. The model is based on overarching value statements that express the worthiness of all individuals, the value of the lived experience of disability and the responsibility of the rehabilitation process to enable client autonomy. Four "values in action" are articulated: caring and respect for the individual and his/her personhood; applying the lived experience of disability; fostering autonomy; and promoting hopefulness. These values have been initially described in another paper based on a specific subset of 15 women living with SCI related to body issues during rehabilitation. This paper builds on this value work and we develop key practices for a progressive rehabilitation culture and model, based on the larger study group of 80 participants (men and women with SCI). This value-based model, when integrated with traditional, physical improvement-focused rehabilitation, has the potential to create a more effective process by offering

  18. What’s Needed from Climate Modeling to Advance Actionable Science for Water Utilities?

    NASA Astrophysics Data System (ADS)

    Barsugli, J. J.; Anderson, C. J.; Smith, J. B.; Vogel, J. M.

    2009-12-01

    “…perfect information on climate change is neither available today nor likely to be available in the future, but … over time, as the threats climate change poses to our systems grow more real, predicting those effects with greater certainty is non-discretionary. We’re not yet at a level at which climate change projections can drive climate change adaptation.” (Testimony of WUCA Staff Chair David Behar to the House Committee on Science and Technology, May 5, 2009) To respond to this challenge, the Water Utility Climate Alliance (WUCA) has sponsored a white paper titled “Options for Improving Climate Modeling to Assist Water Utility Planning for Climate Change. ” This report concerns how investments in the science of climate change, and in particular climate modeling and downscaling, can best be directed to help make climate projections more actionable. The meaning of “model improvement” can be very different depending on whether one is talking to a climate model developer or to a water manager trying to incorporate climate projections in to planning. We first surveyed the WUCA members on present and potential uses of climate model projections and on climate inputs to their various system models. Based on those surveys and on subsequent discussions, we identified four dimensions along which improvement in modeling would make the science more “actionable”: improved model agreement on change in key parameters; narrowing the range of model projections; providing projections at spatial and temporal scales that match water utilities system models; providing projections that water utility planning horizons. With these goals in mind we developed four options for improving global-scale climate modeling and three options for improving downscaling that will be discussed. However, there does not seem to be a single investment - the proverbial “magic bullet” -- which will substantially reduce the range of model projections at the scales at which utility

  19. A new interaction potential for swarming models

    NASA Astrophysics Data System (ADS)

    Carrillo, J. A.; Martin, S.; Panferov, V.

    2013-10-01

    We consider a self-propelled particle system which has been used to describe certain types of collective motion of animals, such as fish schools and bird flocks. Interactions between particles are specified by means of a pairwise potential, repulsive at short ranges and attractive at longer ranges. The exponentially decaying Morse potential is a typical choice, and is known to reproduce certain types of collective motion observed in nature, particularly aligned flocks and rotating mills. We introduce a class of interaction potentials, that we call Quasi-Morse, for which flock and rotating mills states are also observed numerically, however in that case the corresponding macroscopic equations allow for explicit solutions in terms of special functions, with coefficients that can be obtained numerically without solving the particle evolution. We compare the obtained solutions with long-time dynamics of the particle systems and find a close agreement for several types of flock and mill solutions.

  20. A Model of Values and Actions for Personal Knowledge Management

    ERIC Educational Resources Information Center

    Zuber-Skerritt, Ortrun

    2005-01-01

    Purpose: The purpose of this paper is to present a "soft methodology" model in knowledge management that addresses the problem of accessing and managing one particular type of knowledge: personal (implicit/tacit) knowledge. Design/methodology/approach: The model is based on the theories and methodologies of grounded theory, adult learning,…

  1. Model potential calculations of lithium transitions.

    NASA Technical Reports Server (NTRS)

    Caves, T. C.; Dalgarno, A.

    1972-01-01

    Semi-empirical potentials are constructed that have eigenvalues close in magnitude to the binding energies of the valence electron in lithium. The potentials include the long range polarization force between the electron and the core. The corresponding eigenfunctions are used to calculate dynamic polarizabilities, discrete oscillator strengths, photoionization cross sections and radiative recombination coefficients. A consistent application of the theory imposes a modification on the transition operator, but its effects are small for lithium. The method presented can be regarded as a numerical generalization of the widely used Coulomb approximation.

  2. The Use of Conceptual versus Physical Models in Teaching Action Research to Culturally Diverse Student Populations: A Preliminary Analysis.

    ERIC Educational Resources Information Center

    McMurray, Adela J.

    2002-01-01

    Graduate business administration students (n=55) were asked which model they used for action research projects: conceptual or a physical model visually depicting action research. The physical model was favored by 69%; most agreed that it helped them understand the process of action research, was easy to use, and flexibly applied to various…

  3. Acting in solidarity: Testing an extended dual pathway model of collective action by bystander group members.

    PubMed

    Saab, Rim; Tausch, Nicole; Spears, Russell; Cheung, Wing-Yee

    2015-09-01

    We examined predictors of collective action among bystander group members in solidarity with a disadvantaged group by extending the dual pathway model of collective action, which proposes one efficacy-based and one emotion-based path to collective action (Van Zomeren, Spears, Fischer, & Leach, 2004). Based on two proposed functions of social identity performance (Klein, Spears, & Reicher, 2007), we distinguished between the efficacy of collective action at consolidating the identity of a protest movement and its efficacy at achieving social change (political efficacy). We expected identity consolidation efficacy to positively predict collective action tendencies directly and indirectly via political efficacy. We also expected collective action tendencies to be positively predicted by moral outrage and by sympathy in response to disadvantaged outgroup's suffering. These hypotheses were supported in two surveys examining intentions to protest for Palestine in Britain (Study 1), and intentions to attend the June 4th vigil in Hong Kong to commemorate the Tiananmen massacre among a sample of Hong Kong citizens (Study 2). The contributions of these findings to research on the dual pathway model of collective action and the different functions of collective action are discussed. PMID:25406712

  4. Oculomotor learning revisited: a model of reinforcement learning in the basal ganglia incorporating an efference copy of motor actions

    PubMed Central

    Fee, Michale S.

    2012-01-01

    In its simplest formulation, reinforcement learning is based on the idea that if an action taken in a particular context is followed by a favorable outcome, then, in the same context, the tendency to produce that action should be strengthened, or reinforced. While reinforcement learning forms the basis of many current theories of basal ganglia (BG) function, these models do not incorporate distinct computational roles for signals that convey context, and those that convey what action an animal takes. Recent experiments in the songbird suggest that vocal-related BG circuitry receives two functionally distinct excitatory inputs. One input is from a cortical region that carries context information about the current “time” in the motor sequence. The other is an efference copy of motor commands from a separate cortical brain region that generates vocal variability during learning. Based on these findings, I propose here a general model of vertebrate BG function that combines context information with a distinct motor efference copy signal. The signals are integrated by a learning rule in which efference copy inputs gate the potentiation of context inputs (but not efference copy inputs) onto medium spiny neurons in response to a rewarded action. The hypothesis is described in terms of a circuit that implements the learning of visually guided saccades. The model makes testable predictions about the anatomical and functional properties of hypothesized context and efference copy inputs to the striatum from both thalamic and cortical sources. PMID:22754501

  5. The New Vocationalism: A Potential Model.

    ERIC Educational Resources Information Center

    Elliott, Donna; May, Susan A.

    In light of the increasing emphasis on "vocationalism"--preparing students for work--in education and the media today, a model is proposed through which the major components of this "new vocationalism" could be operationalized. The model integrates academic and vocational education. It involves a total system change in education that describes the…

  6. A novel potential therapeutic avenue for autism: Design, synthesis and pharmacophore generation of SSRIs with dual action

    PubMed Central

    Ghoneim, Ola M.; Ibrahim, Diaa A.; El-Deeb, Ibrahim M.; Lee, So Ha; Booth, Raymond G.

    2014-01-01

    Autism symptoms are currently modulated by Selective Serotonin Reuptake Inhibitors (SSRIs). SSRIs slow onset of action limits their efficiency. The established synergistic activity of SSRIs and 5HT1B/1D autoreceptors antagonists motivated us to incorporate SSRIs and 5HT1B/1D antagonists in one ‘hybrid’ molecule. A library of virtual ‘hybrid’ molecules was designed using the tethering technique. A pharmacophore model was generated derived from 16 structurally diverse SSRIs (Ki = 0.013–5000 nM) and used as 3D query. Compounds with fit values (≥2) were chosen for synthesis and subsequent in vitro biological evaluation. Our pharmacophore model is a promising milestone to a class of SSRIs with dual action. PMID:21982496

  7. Combined Hand Gesture — Speech Model for Human Action Recognition

    PubMed Central

    Cheng, Sheng-Tzong; Hsu, Chih-Wei; Li, Jian-Pan

    2013-01-01

    This study proposes a dynamic hand gesture detection technology to effectively detect dynamic hand gesture areas, and a hand gesture recognition technology to improve the dynamic hand gesture recognition rate. Meanwhile, the corresponding relationship between state sequences in hand gesture and speech models is considered by integrating speech recognition technology with a multimodal model, thus improving the accuracy of human behavior recognition. The experimental results proved that the proposed method can effectively improve human behavior recognition accuracy and the feasibility of system applications. Experimental results verified that the multimodal gesture-speech model provided superior accuracy when compared to the single modal versions. PMID:24351628

  8. The potential for multi-disciplinary primary health care services to take action on the social determinants of health: actions and constraints

    PubMed Central

    2013-01-01

    Background The Commission on the Social Determinants of Health and the World Health Organization have called for action to address the social determinants of health. This paper considers the extent to which primary health care services in Australia are able to respond to this call. We report on interview data from an empirical study of primary health care centres in Adelaide and Alice Springs, Australia. Methods Sixty-eight interviews were held with staff and managers at six case study primary health care services, regional health executives, and departmental funders to explore how their work responded to the social determinants of health and the dilemmas in doing so. The six case study sites included an Aboriginal Community Controlled Organisation, a sexual health non-government organisation, and four services funded and managed by the South Australian government. Results While respondents varied in the extent to which they exhibited an understanding of social determinants most were reflexive about the constraints on their ability to take action. Services’ responses to social determinants included delivering services in a way that takes account of the limitations individuals face from their life circumstances, and physical spaces in the primary health care services being designed to do more than simply deliver services to individuals. The services also undertake advocacy for policies that create healthier communities but note barriers to them doing this work. Our findings suggest that primary health care workers are required to transverse “dilemmatic space” in their work. Conclusions The absence of systematic supportive policy, frameworks and structure means that it is hard for PHC services to act on the Commission on the Social Determinants of Health’s recommendations. Our study does, however, provide evidence of the potential for PHC services to be more responsive to social determinants given more support and by building alliances with communities and

  9. Potential mechanisms of action of lithium in bipolar disorder. Current understanding.

    PubMed

    Malhi, Gin S; Tanious, Michelle; Das, Pritha; Coulston, Carissa M; Berk, Michael

    2013-02-01

    Lithium has been used for over half a century for the treatment of bipolar disorder as the archetypal mood stabilizer, and has a wealth of empirical evidence supporting its efficacy in this role. Despite this, the specific mechanisms by which lithium exerts its mood-stabilizing effects are not well understood. Given the inherently complex nature of the pathophysiology of bipolar disorder, this paper aims to capture what is known about the actions of lithium ranging from macroscopic changes in mood, cognition and brain structure, to its effects at the microscopic level on neurotransmission and intracellular and molecular pathways. A comprehensive literature search of databases including MEDLINE, EMBASE and PsycINFO was conducted using relevant keywords and the findings from the literature were then reviewed and synthesized. Numerous studies report that lithium is effective in the treatment of acute mania and for the long-term maintenance of mood and prophylaxis; in comparison, evidence for its efficacy in depression is modest. However, lithium possesses unique anti-suicidal properties that set it apart from other agents. With respect to cognition, studies suggest that lithium may reduce cognitive decline in patients; however, these findings require further investigation using both neuropsychological and functional neuroimaging probes. Interestingly, lithium appears to preserve or increase the volume of brain structures involved in emotional regulation such as the prefrontal cortex, hippocampus and amygdala, possibly reflecting its neuroprotective effects. At a neuronal level, lithium reduces excitatory (dopamine and glutamate) but increases inhibitory (GABA) neurotransmission; however, these broad effects are underpinned by complex neurotransmitter systems that strive to achieve homeostasis by way of compensatory changes. For example, at an intracellular and molecular level, lithium targets second-messenger systems that further modulate neurotransmission. For

  10. Cardiovascular Actions and Therapeutic Potential of Tetramethylpyrazine (Active Component Isolated from Rhizoma Chuanxiong): Roles and Mechanisms

    PubMed Central

    Guo, Ming; Liu, Yue; Shi, Dazhuo

    2016-01-01

    Tetramethylpyrazine (TMP), a pharmacologically active component isolated from the rhizome of the Chinese herb Rhizoma Chuanxiong (Chuanxiong), has been clinically used in China and Southeast Asian countries for the prevention and treatment of cardiovascular diseases (CVDs) for about fifty years. The pharmacological effects of TMP on the cardiovascular system have attracted great interest. Emerging experimental studies and clinical trials have demonstrated that TMP prevents atherosclerosis as well as ischemia-reperfusion injury. The cardioprotective effects of TMP are mainly related to its antioxidant, anti-inflammatory, or calcium-homeostasis effects. This review focuses on the roles and mechanisms of action of TMP in the cardiovascular system and provides a novel perspective on TMP's clinical use. PMID:27314011

  11. Larval therapy from antiquity to the present day: mechanisms of action, clinical applications and future potential

    PubMed Central

    Whitaker, Iain S; Twine, Christopher; Whitaker, Michael J; Welck, Mathew; Brown, Charles S; Shandall, Ahmed

    2007-01-01

    When modern medicine fails, it is often useful to draw ideas from ancient treatments. The therapeutic use of fly larvae to debride necrotic tissue, also known as larval therapy, maggot debridement therapy or biosurgery, dates back to the beginnings of civilisation. Despite repeatedly falling out of favour largely because of patient intolerance to the treatment, the practice of larval therapy is increasing around the world because of its efficacy, safety and simplicity. Clinical indications for larval treatment are varied, but, in particular, are wounds infected with multidrug‐resistant bacteria and the presence of significant co‐morbidities precluding surgical intervention. The flies most often used in larval therapy are the facultative calliphorids, with the greenbottle blowfly (Lucilia sericata) being the most widely used species. This review summarises the fascinating and turbulent history of larval therapy from its origin to the present day, including mechanisms of action and evidence for its clinical applications. It also explores future research directions. PMID:17551073

  12. Assessing potential targets of calcium action in light-modulated gravitropism

    NASA Technical Reports Server (NTRS)

    Roux, S. J.

    1995-01-01

    Light, through the mediation of the pigment phytochrome, modulates the gravitropic response of the shoots and roots of many plants. The transduction of both light and gravity stimuli appears to involve Ca(2+)-regulated steps, one or more of which may represent points of intersection between the two transduction chains. To be confident that Ca2+ plays a critical role in stimulus-response coupling for gravitropism, it will be important to identify specific targets of Ca2+ action whose function can be clearly linked to the regulation of growth. Calcium typically exerts its influence on cell metabolism through binding to and activating key regulatory proteins. The three best characterized of these proteins in plants are the calmodulins, calcium-dependent protein kinases, and annexins. In this review we summarize what is known about the structure and function of these proteins and speculate on how their activation by Ca2+ could influence the differential growth response of gravitropism.

  13. Metal-organic frameworks: mechanisms of antibacterial action and potential applications.

    PubMed

    Wyszogrodzka, Gabriela; Marszałek, Bartosz; Gil, Barbara; Dorożyński, Przemysław

    2016-06-01

    The growing resistance of pathogens to conventional antibiotics has become a public health problem and raises the need to seek new effective solutions. Metal-organic frameworks (MOFs) are porous, hybrid materials comprising metal ions linked by organic binding ligands. The possibility of using a variety of chemical building components in MOFs enables the formation of structures with desired properties. They can act as a reservoir of metal ions, providing their gradual release and resulting in a sustained antibacterial action analogous to that proposed for metal/metal oxide nanoparticles (NPs) but different to that of antibiotics. These features make MOFs promising candidates for pharmaceutical and biomedical applications, as illustrated by examples discussed in this review. PMID:27091434

  14. Nuclear Targeting with an Auger Electron Emitter Potentiates the Action of a Widely Used Antineoplastic Drug.

    PubMed

    Imstepf, Sebastian; Pierroz, Vanessa; Raposinho, Paula; Bauwens, Matthias; Felber, Michael; Fox, Thomas; Shapiro, Adam B; Freudenberg, Robert; Fernandes, Célia; Gama, Sofia; Gasser, Gilles; Motthagy, Felix; Santos, Isabel R; Alberto, Roger

    2015-12-16

    We present the combination of the clinically well-proven chemotherapeutic agent, Doxorubicin, and (99m)Tc, an Auger and internal conversion electron emitter, into a dual-action agent for therapy. Chemical conjugation of Doxorubicin to (99m)Tc afforded a construct which autonomously ferries a radioactive payload into the cell nucleus. At this site, damage is exerted by dose deposition from Auger radiation. The (99m)Tc-conjugate exhibited a dose-dependent inhibition of survival in a selected panel of cancer cells and an in vivo study in healthy mice evidenced a biodistribution which is comparable to that of the parent drug. The homologous Rhenium conjugate was found to effectively bind to DNA, inhibited human Topoisomerase II, and exhibited cytotoxicity in vitro. The collective in vitro and in vivo data demonstrate that the presented metallo-conjugates closely mimic native Doxorubicin. PMID:26473388

  15. Model to characterize strain generated potentials in bone.

    PubMed

    Mahmud, F A; Hastings, G W; Martini, M

    1988-01-01

    A model has been developed to characterize the strain generated potentials (SGPs) in bone. The model relates the SGP signal to the rotation (reorientation) of the spontaneous dipoles of bone in response to mechanical deformation. The effects of bone structural conditions and the measuring circuitry on the recorded potential are both accounted for by the model. PMID:3347035

  16. Mosquito larvicidal and pupaecidal potential of prodigiosin from Serratia marcescens and understanding its mechanism of action.

    PubMed

    Suryawanshi, Rahul K; Patil, Chandrashekhar D; Borase, Hemant P; Narkhede, Chandrakant P; Salunke, Bipinchandra K; Patil, Satish V

    2015-09-01

    Mosquitoes spread lethal diseases like malaria and dengue fever to humans. Considering mosquito vector control as one of the best alternatives to reduce new infections, here we have analyzed the effect of purified pigment prodigiosin extracted from Serratia marcescens (NMCC 75) against larval and pupal stages of Aedes aegypti and Anopheles stephensi mosquitoes. Mosquito larvicidal activities of purified prodigiosin revealed LC50 values of 14 ± 1.2, 15.6 ± 1.48, 18 ± 1.3, 21 ± 0.87 µg/ml against early IInd, IIIrd, IVth instar and pupal stages of Ae. aegypti, respectively. LC50 values for An. stephensi were found to be 19.7 ± 1.12, 24.7 ± 1.47, 26.6 ± 1.67, 32.2 ± 1.79 µg/ml against early IInd, IIIrd, IVth instar and pupae of An. stephensi, respectively. Further investigations toward understanding modes of action revealed variations in the activities of esterases, acetylcholine esterases, phosphatases, proteases and total proteins in the fourth instar larvae of Ae. aegypti indicating intrinsic difference in biochemical features due to prodigiosin treatment. Although there was no inhibition of enzymes like catalase and oxidase but may have profound inhibitory effect on carbonic anhydrase or H(+)-V-ATPase which is indicated by change in the pH of midgut and caeca of mosquito larvae. This reduced pH may be possibly due to the proton pump inhibitory activity of prodigiosin. Pure prodigiosin can prove to be an important molecule for mosquito control at larval and pupal stages of Ae. aegypti and An. stephensi. This is the first report on the mosquito pupaecidal activity of prodigiosin and its possible mechanism of action. PMID:26267052

  17. HMGB1 Inhibition During Zymosan-Induced Inflammation: The Potential Therapeutic Action of Riboflavin.

    PubMed

    Mazur-Bialy, Agnieszka Irena; Pocheć, Ewa

    2016-04-01

    Sepsis, also known as systemic inflammatory response syndrome, is a life-threatening condition caused by a pathogenic agent and leading to multiple organ dysfunction syndrome. One of the factors responsible for the excessive intensification of the inflammatory response in the course of inflammation is high-mobility group protein B1 (HMGB1). HMG-1 is a nuclear protein which, after being released to the intercellular space, has a highly pro-inflammatory effect and acts as a late mediator of lethal damage. The purpose of this study was to examine whether the anti-inflammatory action of riboflavin is accompanied by inhibition of HMGB1 release during peritoneal inflammation and zymosan stimulation of macrophages. Peritonitis was induced in male BALB/c and C57BL/6J mice via intraperitoneal injection of zymosan (40 mg/kg). RAW 264.7 macrophages were activated with zymosan (250 µg/ml). Riboflavin (mice, 50 mg/kg; RAW 264.7, 25 µg/ml) was administered 30 min before zymosan, simultaneously with, or 2, 4, 6 h after zymosan. Additionally, mRNA expression of HMGB1 and its intracellular and serum levels were evaluated. The research showed that riboflavin significantly reduces both the expression and the release of HMGB1; however, the effect of riboflavin was time-dependent. The greatest efficacy was found when riboflavin was given 30 min prior to zymosan, and also 2 and 4 h (C57BL/6J; RAW 264.7) or 4 and 6 h (BALB/c) after zymosan. Research showed that riboflavin influences the level of HMGB1 released in the course of inflammation; however, further study is necessary to determine its mechanisms of action. PMID:26445809

  18. The chemopreventive action of equol enantiomers in a chemically induced animal model of breast cancer

    PubMed Central

    Brown, Nadine M.; Belles, Carrie A.; Lindley, Stephanie L.; Zimmer-Nechemias, Linda D.; Zhao, Xueheng; Witte, David P.; Kim, Mi-Ok; Setchell, Kenneth D.R.

    2010-01-01

    We describe for the first time the chemopreventive effects of S-(−)equol and R-(+)equol, diastereoisomers with contrasting affinities for estrogen receptors (ERs). S-(−)equol, a ligand for ERβ, is an intestinally derived metabolite formed by many humans and by rodents consuming diets containing soy isoflavones. Whether the well-documented chemopreventive effect of a soy diet could be explained by equol's action was unclear because neither diastereoisomers had been tested in animal models of chemoprevention. Sprague–Dawley rats (n = 40–41 per group) were fed a soy-free AIN-93G diet or an AIN-93G diet supplemented with 250 mg/kg of S-(−)equol or R-(+)equol beginning day 35. On day 50, mammary tumors were induced by dimethylbenz[a]anthracene and thereafter, animals were palpated for number and location of tumors. On day 190, animals were killed and mammary tumors were removed and verified by histology, and the degree of invasiveness and differentiation was determined. S-(−)equol and R-(+)equol plasma concentrations measured on days 35, 100 and 190 by tandem mass spectrometry confirmed diet compliance and no biotransformation of either diastereoisomer. In this model, S-(−)equol had no chemopreventive action, nor was it stimulatory. In contrast, R-(+)equol compared with Controls reduced palpable tumors (P = 0.002), resulted in 43% fewer tumors (P = 0.004), increased tumor latency (88.5 versus 66 days, P = 0.003), and tumors were less invasive but showed no difference in pattern grade or mitosis. Both enantiomers had no effect on absolute uterine weight but caused a significant reduction in body weight gain. In conclusion, the novel finding that the unnatural enantiomer, R-(+)equol, was potently chemopreventive warrants investigation of its potential for breast cancer prevention and treatment. PMID:20110282

  19. Computational Model of Primary Visual Cortex Combining Visual Attention for Action Recognition.

    PubMed

    Shu, Na; Gao, Zhiyong; Chen, Xiangan; Liu, Haihua

    2015-01-01

    Humans can easily understand other people's actions through visual systems, while computers cannot. Therefore, a new bio-inspired computational model is proposed in this paper aiming for automatic action recognition. The model focuses on dynamic properties of neurons and neural networks in the primary visual cortex (V1), and simulates the procedure of information processing in V1, which consists of visual perception, visual attention and representation of human action. In our model, a family of the three-dimensional spatial-temporal correlative Gabor filters is used to model the dynamic properties of the classical receptive field of V1 simple cell tuned to different speeds and orientations in time for detection of spatiotemporal information from video sequences. Based on the inhibitory effect of stimuli outside the classical receptive field caused by lateral connections of spiking neuron networks in V1, we propose surround suppressive operator to further process spatiotemporal information. Visual attention model based on perceptual grouping is integrated into our model to filter and group different regions. Moreover, in order to represent the human action, we consider the characteristic of the neural code: mean motion map based on analysis of spike trains generated by spiking neurons. The experimental evaluation on some publicly available action datasets and comparison with the state-of-the-art approaches demonstrate the superior performance of the proposed model. PMID:26132270

  20. Computational Model of Primary Visual Cortex Combining Visual Attention for Action Recognition

    PubMed Central

    Shu, Na; Gao, Zhiyong; Chen, Xiangan; Liu, Haihua

    2015-01-01

    Humans can easily understand other people’s actions through visual systems, while computers cannot. Therefore, a new bio-inspired computational model is proposed in this paper aiming for automatic action recognition. The model focuses on dynamic properties of neurons and neural networks in the primary visual cortex (V1), and simulates the procedure of information processing in V1, which consists of visual perception, visual attention and representation of human action. In our model, a family of the three-dimensional spatial-temporal correlative Gabor filters is used to model the dynamic properties of the classical receptive field of V1 simple cell tuned to different speeds and orientations in time for detection of spatiotemporal information from video sequences. Based on the inhibitory effect of stimuli outside the classical receptive field caused by lateral connections of spiking neuron networks in V1, we propose surround suppressive operator to further process spatiotemporal information. Visual attention model based on perceptual grouping is integrated into our model to filter and group different regions. Moreover, in order to represent the human action, we consider the characteristic of the neural code: mean motion map based on analysis of spike trains generated by spiking neurons. The experimental evaluation on some publicly available action datasets and comparison with the state-of-the-art approaches demonstrate the superior performance of the proposed model. PMID:26132270

  1. Renormalized effective actions for the O(N) model at next-to-leading order of the 1/N expansion

    SciTech Connect

    Fejos, G.; Patkos, A.; Szep, Zs.

    2009-07-15

    A fully explicit renormalized quantum action functional is constructed for the O(N) model in the auxiliary field formulation at next-to-leading order (NLO) of the 1/N expansion. Counterterms are consistently and explicitly derived for arbitrary constant vacuum expectation value of the scalar and auxiliary fields. The renormalized NLO pion propagator is exact at this order and satisfies Goldstone's theorem. Elimination of the auxiliary field sector at the level of the functional provides with O(N{sup 0}) accuracy the renormalized effective action of the model in terms of the original variables. Alternative elimination of the pion and sigma propagators provides the renormalized NLO effective potential for the expectation values of the N vector and of the auxiliary field with the same accuracy.

  2. The spatio-temporal characteristics of action potential initiation in layer 5 pyramidal neurons: a voltage imaging study.

    PubMed

    Popovic, Marko A; Foust, Amanda J; McCormick, David A; Zecevic, Dejan

    2011-09-01

    The spatial pattern of Na(+) channel clustering in the axon initial segment (AIS) plays a critical role in tuning neuronal computations, and changes in Na(+) channel distribution have been shown to mediate novel forms of neuronal plasticity in the axon. However, immunocytochemical data on channel distribution may not directly predict spatio-temporal characteristics of action potential initiation, and prior electrophysiological measures are either indirect (extracellular) or lack sufficient spatial resolution (intracellular) to directly characterize the spike trigger zone (TZ). We took advantage of a critical methodological improvement in the high sensitivity membrane potential imaging (V(m) imaging) technique to directly determine the location and length of the spike TZ as defined in functional terms. The results show that in mature axons of mouse cortical layer 5 pyramidal cells, action potentials initiate in a region ∼20 μm in length centred between 20 and 40 μm from the soma. From this region, the AP depolarizing wave invades initial nodes of Ranvier within a fraction of a millisecond and propagates in a saltatory fashion into axonal collaterals without failure at all physiologically relevant frequencies. We further demonstrate that, in contrast to the saltatory conduction in mature axons, AP propagation is non-saltatory (monotonic) in immature axons prior to myelination. PMID:21669974

  3. Potentiation of bradykinin action on smooth muscle by a scorpion venom extract.

    PubMed

    Araujo, R L; Gomez, M V

    1976-08-01

    Gel filtration of the water extract of the venom of the scorpion T. serrulatus showed four peaks; the first peak (P1) is devoid of toxic activity but increases the bradykinin-induced contraction of isolated rat uterus and guinea-pig ileum. The stepwise fractionation of the pooled P1 peak was performed in a DEAE-cellulose column and the bradykinin potentiating activity was found in the second protein peak. Finger-printing of this material showed that the bradykinin potentiating material migrates to the anode, giving two spots when submitted to chromatography, the activity being found in the spot that presents the greatest Rf. The potentiator is destroyed by heating at 97 degrees C, is not dialysable and is destroyed by incubation with pronase. Some of these properties differentiate it from the BPF's from snake venoms. PMID:976731

  4. Building a Model PE Curriculum: Education Reform in Action

    ERIC Educational Resources Information Center

    Moore, John

    2012-01-01

    The blueprint to build a model physical education (PE) curriculum begins by establishing a sound curricular foundation based on a lesson plan template that incorporates clear and concise program goals, the alignment of lessons to state or national content standards, and the collection, analysis and use of objective assessment data that informs…

  5. Teachers' Practices and Mental Models: Transformation through Reflection on Action

    ERIC Educational Resources Information Center

    Manrique, María Soledad; Sánchez Abchi, Verónica

    2015-01-01

    This contribution explores the relationship between teaching practices, teaching discourses and teachers' implicit representations and mental models and the way these dimensions change through teacher education (T.E). In order to study these relationships, and based on the assumptions that representations underlie teaching practices and that T.E…

  6. Characteristics of Effective Training: Developing a Model To Motivate Action.

    ERIC Educational Resources Information Center

    Wise, Dena; Ezell, Patsy

    2003-01-01

    The Parenting and Consumer Education project identified effective models for training welfare-to-work facilitators. Premises were the importance of process, learner responsibility, and improvement of social networks. Effective training was learner focused, inspiring, and motivating; demonstrated productive behaviors and effective life skills; and…

  7. Community Reintegration: The Value of Educational-Action-Training Models.

    ERIC Educational Resources Information Center

    Versluys, Hilda P.

    1984-01-01

    The article describes the principles that guide program development, the use of therapeutic and educational activities, and the components of transitional program models for disabled individuals re-entering the community following discharge from rehabilitation facilities. The role of the occupatonal therapist in successful reintegration is…

  8. Preparing Women Leaders: The Astin Social Change Model in Action.

    ERIC Educational Resources Information Center

    Cook, Jennifer E.; Young, Madelyn V.

    1999-01-01

    The Converse College Institute for Leadership has used the Astin Social Change Model to create a holistic approach to women's leadership education. This article describes the program framework and content, which blends academics and out-of-classroom experiences in an interconnected approach to leadership training. (Author/DB)

  9. Accountability: An Action Model for the Public Schools.

    ERIC Educational Resources Information Center

    DeMont, Bill[ie; DeMont, Roger

    The model proposed in this book specifies that there are four types of interrelated practices that determine the extent to which accountability is realized. These are (1) the identification of primary accountability agents and their respective program responsibilities, (2) the execution of internal program reviews by those program officers, (3)…

  10. Visual Stimuli Evoked Action Potentials Trigger Rapidly Propagating Dendritic Calcium Transients in the Frog Optic Tectum Layer 6 Neurons.

    PubMed

    Svirskis, Gytis; Baranauskas, Gytis; Svirskiene, Natasa; Tkatch, Tatiana

    2015-01-01

    The superior colliculus in mammals or the optic tectum in amphibians is a major visual information processing center responsible for generation of orientating responses such as saccades in monkeys or prey catching avoidance behavior in frogs. The conserved structure function of the superior colliculus the optic tectum across distant species such as frogs, birds monkeys permits to draw rather general conclusions after studying a single species. We chose the frog optic tectum because we are able to perform whole-cell voltage-clamp recordings fluorescence imaging of tectal neurons while they respond to a visual stimulus. In the optic tectum of amphibians most visual information is processed by pear-shaped neurons possessing long dendritic branches, which receive the majority of synapses originating from the retinal ganglion cells. Since the first step of the retinal input integration is performed on these dendrites, it is important to know whether this integration is enhanced by active dendritic properties. We demonstrate that rapid calcium transients coinciding with the visual stimulus evoked action potentials in the somatic recordings can be readily detected up to the fine branches of these dendrites. These transients were blocked by calcium channel blockers nifedipine CdCl2 indicating that calcium entered dendrites via voltage-activated L-type calcium channels. The high speed of calcium transient propagation, >300 μm in <10 ms, is consistent with the notion that action potentials, actively propagating along dendrites, open voltage-gated L-type calcium channels causing rapid calcium concentration transients in the dendrites. We conclude that such activation by somatic action potentials of the dendritic voltage gated calcium channels in the close vicinity to the synapses formed by axons of the retinal ganglion cells may facilitate visual information processing in the principal neurons of the frog optic tectum. PMID:26414356

  11. Visual Stimuli Evoked Action Potentials Trigger Rapidly Propagating Dendritic Calcium Transients in the Frog Optic Tectum Layer 6 Neurons

    PubMed Central

    Svirskis, Gytis; Baranauskas, Gytis; Svirskiene, Natasa; Tkatch, Tatiana

    2015-01-01

    The superior colliculus in mammals or the optic tectum in amphibians is a major visual information processing center responsible for generation of orientating responses such as saccades in monkeys or prey catching avoidance behavior in frogs. The conserved structure function of the superior colliculus the optic tectum across distant species such as frogs, birds monkeys permits to draw rather general conclusions after studying a single species. We chose the frog optic tectum because we are able to perform whole-cell voltage-clamp recordings fluorescence imaging of tectal neurons while they respond to a visual stimulus. In the optic tectum of amphibians most visual information is processed by pear-shaped neurons possessing long dendritic branches, which receive the majority of synapses originating from the retinal ganglion cells. Since the first step of the retinal input integration is performed on these dendrites, it is important to know whether this integration is enhanced by active dendritic properties. We demonstrate that rapid calcium transients coinciding with the visual stimulus evoked action potentials in the somatic recordings can be readily detected up to the fine branches of these dendrites. These transients were blocked by calcium channel blockers nifedipine CdCl2 indicating that calcium entered dendrites via voltage-activated L-type calcium channels. The high speed of calcium transient propagation, >300 μm in <10 ms, is consistent with the notion that action potentials, actively propagating along dendrites, open voltage-gated L-type calcium channels causing rapid calcium concentration transients in the dendrites. We conclude that such activation by somatic action potentials of the dendritic voltage gated calcium channels in the close vicinity to the synapses formed by axons of the retinal ganglion cells may facilitate visual information processing in the principal neurons of the frog optic tectum. PMID:26414356

  12. Loss of Local Astrocyte Support Disrupts Action Potential Propagation and Glutamate Release Synchrony from Unmyelinated Hippocampal Axon Terminals In Vitro

    PubMed Central

    Sobieski, Courtney; Jiang, Xiaoping; Crawford, Devon C.

    2015-01-01

    Neuron–astrocyte interactions are critical for proper CNS development and function. Astrocytes secrete factors that are pivotal for synaptic development and function, neuronal metabolism, and neuronal survival. Our understanding of this relationship, however, remains incomplete due to technical hurdles that have prevented the removal of astrocytes from neuronal circuits without changing other important conditions. Here we overcame this obstacle by growing solitary rat hippocampal neurons on microcultures that were comprised of either an astrocyte bed (+astrocyte) or a collagen bed (−astrocyte) within the same culture dish. −Astrocyte autaptic evoked EPSCs, but not IPSCs, displayed an altered temporal profile, which included increased synaptic delay, increased time to peak, and severe glutamate release asynchrony, distinct from previously described quantal asynchrony. Although we observed minimal alteration of the somatically recorded action potential waveform, action potential propagation was altered. We observed a longer latency between somatic initiation and arrival at distal locations, which likely explains asynchronous EPSC peaks, and we observed broadening of the axonal spike, which likely underlies changes to evoked EPSC onset. No apparent changes in axon structure were observed, suggesting altered axonal excitability. In conclusion, we propose that local astrocyte support has an unappreciated role in maintaining glutamate release synchrony by disturbing axonal signal propagation. SIGNIFICANCE STATEMENT Certain glial cell types (oligodendrocytes, Schwann cells) facilitate the propagation of neuronal electrical signals, but a role for astrocytes has not been identified despite many other functions of astrocytes in supporting and modulating neuronal signaling. Under identical global conditions, we cultured neurons with or without local astrocyte support. Without local astrocytes, glutamate transmission was desynchronized by an alteration of the waveform

  13. 4-bromopropofol decreases action potential generation in spinal neurons by inducing a glycine receptor‐mediated tonic conductance

    PubMed Central

    Eckle, V S; Grasshoff, C; Mirakaj, V; O'Neill, P M; Berry, N G; Leuwer, M; Antkowiak, B

    2014-01-01

    Background and Purpose Impaired function of spinal strychnine-sensitive glycine receptors gives rise to chronic pain states and movement disorders. Therefore, increased activity of glycine receptors should help to treat such disorders. Although compounds targeting glycine receptors with a high selectivity are lacking, halogenated analogues of propofol have recently been considered as potential candidates. Therefore we asked whether 4-bromopropofol attenuated the excitability of spinal neurons by promoting glycine receptor-dependent inhibition. Experimental Approach The actions of sub-anaesthetic concentrations of propofol and 4-bromopropofol were investigated in spinal tissue cultures prepared from mice. Drug-induced alterations in action potential firing were monitored by extracellular multi-unit recordings. The effects on GABAA and glycine receptor-mediated inhibition were quantified by whole-cell voltage-clamp recordings. Key Results Low concentrations of 4-bromopropofol (50 nM) reduced action potential activity of ventral horn neurons by about 30%, compared with sham-treated slices. This effect was completely abolished by strychnine (1 μM). In voltage-clamped neurons, 4-bromopropofol activated glycine receptors, generating a tonic current of 65 ± 10 pA, while GABAA- and glycine receptor-mediated synaptic transmission remained unaffected. Conclusions and Implications The highest glycine levels in the CNS are found in the ventral horn of the spinal cord, a region mediating pain-induced motor reflexes and participating in the control of muscle tone. 4-Bromopropofol may serve as a starting point for the development of non-sedative, non-addictive, muscle relaxants and analgesics to be used to treat low back pain. PMID:25131750

  14. Evaluating the Pedagogical Potential of Hybrid Models

    ERIC Educational Resources Information Center

    Levin, Tzur; Levin, Ilya

    2013-01-01

    The paper examines how the use of hybrid models--that consist of the interacting continuous and discrete processes--may assist in teaching system thinking. We report an experiment in which undergraduate students were asked to choose between a hybrid and a continuous solution for a number of control problems. A correlation has been found between…

  15. Overexpression of the Large-Conductance, Ca2+-Activated K+ (BK) Channel Shortens Action Potential Duration in HL-1 Cardiomyocytes

    PubMed Central

    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. PMID:26091273

  16. A discriminative model of motion and cross ratio for view-invariant action recognition.

    PubMed

    Huang, Kaiqi; Zhang, Yeying; Tan, Tieniu

    2012-04-01

    Action recognition is very important for many applications such as video surveillance, human-computer interaction, and so on; view-invariant action recognition is hot and difficult as well in this field. In this paper, a new discriminative model is proposed for video-based view-invariant action recognition. In the discriminative model, motion pattern and view invariants are perfectly fused together to make a better combination of invariance and distinctiveness. We address a series of issues, including interest point detection in image sequence, motion feature extraction and description, and view-invariant calculation. First, motion detection is used to extract motion information from videos, which is much more efficient than traditional background modeling and tracking-based methods. Second, as for feature representation, we exact variety of statistical information from motion and view-invariant feature based on cross ratio. Last, in the action modeling, we apply a discriminative probabilistic model-hidden conditional random field to model motion patterns and view invariants, by which we could fuse the statistics of motion and projective invariability of cross ratio in one framework. Experimental results demonstrate that our method can improve the ability to distinguish different categories of actions with high robustness to view change in real circumstances. PMID:22438508

  17. Ameliorating treatment-refractory depression with intranasal ketamine: potential NMDA receptor actions in the pain circuitry representing mental anguish.

    PubMed

    Opler, Lewis A; Opler, Mark G A; Arnsten, Amy F T

    2016-02-01

    This article reviews the antidepressant actions of ketamine, an N-methyl-D-aspartame glutamate receptor (NMDAR) antagonist, and offers a potential neural mechanism for intranasal ketamine's ultra-rapid actions based on the key role of NMDAR in the nonhuman primate prefrontal cortex (PFC). Although intravenous ketamine infusions can lift mood within hours, the current review describes how intranasal ketamine administration can have ultra-rapid antidepressant effects, beginning within minutes (5-40 minutes) and lasting hours, but with repeated treatments needed for sustained antidepressant actions. Research in rodents suggests that increased synaptogenesis in PFC may contribute to the prolonged benefit of ketamine administration, beginning hours after administration. However, these data cannot explain the relief that occurs within minutes of intranasal ketamine delivery. We hypothesize that the ultra-rapid effects of intranasal administration in humans may be due to ketamine blocking the NMDAR circuits that generate the emotional representations of pain (eg, Brodmann Areas 24 and 25, insular cortex), cortical areas that can be overactive in depression and which sit above the nasal epithelium. In contrast, NMDAR blockade in the dorsolateral PFC following systemic administration of ketamine may contribute to cognitive deficits. This novel view may help to explain how intravenous ketamine can treat the symptoms of depression yet worsen the symptoms of schizophrenia. PMID:25619798

  18. Lactate Transport and Receptor Actions in Retina: Potential Roles in Retinal Function and Disease.

    PubMed

    Kolko, Miriam; Vosborg, Fia; Henriksen, Ulrik L; Hasan-Olive, Md Mahdi; Diget, Elisabeth Holm; Vohra, Rupali; Gurubaran, Iswariya Raja Sridevi; Gjedde, Albert; Mariga, Shelton Tendai; Skytt, Dorte M; Utheim, Tor Paaske; Storm-Mathisen, Jon; Bergersen, Linda H

    2016-06-01

    In retina, like in brain, lactate equilibrates across cell membranes via monocarboxylate transporters and in the extracellular space by diffusion, forming a basis for the action of lactate as a transmitter of metabolic signals. In the present paper, we argue that the lactate receptor GPR81, also known as HCAR1, may contribute importantly to the control of retinal cell functions in health and disease. GPR81, a G-protein coupled receptor, is known to downregulate cAMP both in adipose and nervous tissue. The receptor also acts through other down-stream mechanisms to control functions, such as excitability, metabolism and inflammation. Recent publications predict effects of the lactate receptor on neurodegeneration. Neurodegenerative diseases in retina, where the retinal ganglion cells die, notably glaucoma and diabetic retinopathy, may be linked to disturbed lactate homeostasis. Pilot studies reveal high GPR81 mRNA in retina and indicate GPR81 localization in Müller cells and retinal ganglion cells. Moreover, monocarboxylate transporters are expressed in retinal cells. We envision that lactate receptors and transporters could be useful future targets of novel therapeutic strategies to protect neurons and prevent or counteract glaucoma as well as other retinal diseases. PMID:26677077

  19. Immunomodulatory effects of fluoxetine: A new potential pharmacological action for a classic antidepressant drug?

    PubMed

    Di Rosso, María Emilia; Palumbo, María Laura; Genaro, Ana María

    2016-07-01

    Selective serotonin reuptake inhibitors are frequently used antidepressants. In particular, fluoxetine is usually chosen for the treatment of the symptoms of depression, obsessive-compulsive, panic attack and bulimia nervosa. Antidepressant therapy has been associated with immune dysfunction. However, there is contradictory evidence about the effect of fluoxetine on the immune system. Experimental findings indicate that lymphocytes express the serotonin transporter. Moreover it has been shown that fluoxetine is able to modulate the immune function through a serotonin-dependent pathway and through a novel independent mechanism. In addition, several studies have shown that fluoxetine can alter tumor cell viability. Thus, it was recently demonstrated in vivo that chronic fluoxetine treatment inhibits tumor growth by increasing antitumor T-cell activity. Here we briefly review some of the literature referring to how fluoxetine is able to modify, for better or worse, the functionality of the immune system. These results of our analysis point to the relevance of the novel pharmacological action of this drug as an immunomodulator helping to treat several pathologies in which immune deficiency and/or deregulation is present. PMID:26644208

  20. Direct inhibition of arcuate proopiomelanocortin neurons: a potential mechanism for the orexigenic actions of dynorphin

    PubMed Central

    Zhang, Xiaobing; van den Pol, Anthony N

    2013-01-01

    Dynorphin, an endogenous ligand of kappa (κ) opioid receptors, has multiple roles in the brain, and plays a positive role in energy balance and food intake. However, the mechanism for this is unclear. With immunocytochemistry, we find that axonal dynorphin immunoreactivity in the arcuate nucleus is strong, and that a large number of dynorphin-immunoreactive boutons terminate on or near anorexigenic proopiomelanocortin (POMC) cells. Here we provide evidence from whole-cell patch-clamp recording that dynorphin-A (Dyn-A) directly and dose-dependently inhibits arcuate nucleus POMC neurons. Dyn-A inhibition was eliminated by the κ opioid receptor antagonist nor-BNI, but not by the μ receptor antagonist CTAP. The inhibitory effect was mimicked by the κ2 receptor agonist GR89696, but not by the κ1 receptor agonist U69593. No presynaptic effect of κ2 agonists was found. These results suggest that Dyn-A inhibits POMC neurons through activation of the κ2 opioid receptor. In whole-cell voltage clamp, Dyn-A opened G-protein-coupled inwardly rectifying potassium (GIRK)-like channels on POMC neurons. Dynorphin attenuated glutamate and GABA neurotransmission to POMC neurons. In contrast to the strong inhibition of POMC neurons by Dyn-A, we found a weaker direct inhibitory effect of Dyn-A on arcuate nucleus neuropeptide Y (NPY) neurons mediated by both κ1 and κ2 receptors. Taken together, these results indicate a direct inhibitory effect of Dyn-A on POMC neurons through activation of the κ2 opioid receptor and GIRK channels. A number of orexigenic hypothalamic neurons release dynorphin along with other neuropeptides. The inhibition of anorexigenic POMC neurons may be one mechanism underlying the orexigenic actions of dynorphin. PMID:23318874

  1. In vitro antimalarial activity and chloroquine potentiating action of two bisbenzylisoquinoline enantiomer alkaloids isolated from Strychnopsis thouarsii and Spirospermum penduliflorum.

    PubMed

    Ratsimamanga-Urverg, S; Rasoanaivo, P; Ramiaramanana, L; Milijaona, R; Rafatro, H; Verdier, F; Rakoto-Ratsimamanga, A; Le Bras, J

    1992-12-01

    The bisbenzylisoquinolines 7-O-demethyltetrandrine and limacine, respectively, isolated from Strychnopsis thouarsii Baill. and Spirospermum penduliflorum Thou. were evaluated for their intrinsic antimalarial activity in vitro and chloroquine potentiating action against the chloroquine-resistant Plasmodium falciparum FCM 29 originating from Cameroon. They both showed significant antiplasmodial potency in vitro with very similar IC50 values of respectively, 740 nM and 789 nM (IC50 = 214 nM for chloroquine used as standard drug), which demonstrated that the stereochemistry of the C-1 and C-1' configuration likely plays a role in the chloroquine potentiating effect of these drugs. If confirmed in vivo, these results may account for the traditional use of the two plants as antimalarials and adjuvant to chloroquine in Madagascan folklore remedies. PMID:1484894

  2. MOAtox: A Comprehensive Mode of Action and Acute Aquatic Toxicity Database for Predictive Model Development

    EPA Science Inventory

    tThe mode of toxic action (MOA) has been recognized as a key determinant of chemical toxicity andas an alternative to chemical class-based predictive toxicity modeling. However, the development ofquantitative structure activity relationship (QSAR) and other models has been limite...

  3. Operationalizing the Concept of Value--An Action Research-Based Model

    ERIC Educational Resources Information Center

    Naslund, Dag; Olsson, Annika; Karlsson, Sture

    2006-01-01

    Purpose: While the importance of measuring customer satisfaction levels is well established, less research exists on how organizations operationalize such knowledge. The purpose of this paper is to describe an action research (AR) case study resulting in a workshop model to operationalize the concept of value. The model facilitates organizational…

  4. Education as Sustainability: An Action Research Study of the Burns Model of Sustainability Pedagogy

    ERIC Educational Resources Information Center

    Burns, Heather

    2009-01-01

    Postsecondary teaching and learning must be reoriented to equip learners with the knowledge, skills, and values they will need for creating a more sustainable world. This action research study examined the effects of implementing the "Burns model of sustainability pedagogy" in university courses taught by the researcher. This model is comprised of…

  5. Contribution of ion currents to beat-to-beat variability of action potential duration in canine ventricular myocytes.

    PubMed

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

    2015-07-01

    Although beat-to-beat variability (short-term variability, SV) of action potential duration (APD) is considered as a predictor of imminent cardiac arrhythmias, the underlying mechanisms are still not clear. In the present study, therefore, we aimed to determine the role of the major cardiac ion currents, APD, stimulation frequency, and changes in the intracellular Ca(2+) concentration ([Ca(2+)]i) on the magnitude of SV. Action potentials were recorded from isolated canine ventricular cardiomyocytes using conventional microelectrode techniques. SV was an exponential function of APD, when APD was modified by current injections. Drug effects were characterized as relative SV changes by comparing the drug-induced changes in SV to those in APD according to the exponential function obtained with current pulses. Relative SV was increased by dofetilide, HMR 1556, nisoldipine, and veratridine, while it was reduced by BAY K8644, tetrodotoxin, lidocaine, and isoproterenol. Relative SV was also increased by increasing the stimulation frequency and [Ca(2+)]i. In summary, relative SV is decreased by ion currents involved in the negative feedback regulation of APD (I Ca, I Ks, and I Kr), while it is increased by I Na and I to. We conclude that drug-induced effects on SV should be evaluated in relation with the concomitant changes in APD. Since relative SV was decreased by ion currents playing critical role in the negative feedback regulation of APD, blockade of these currents, or the beta-adrenergic pathway, may carry also some additional proarrhythmic risk in addition to their well-known antiarrhythmic action. PMID:25081243

  6. Nuclear Winter Revisited: Still the Most Dangerous Potential Environmental Consequence of Human Actions

    NASA Astrophysics Data System (ADS)

    Robock, A.; Oman, L.; Stenchikov, G.

    2006-12-01

    Twenty years ago, the results of climate model simulations of the response to smoke and dust from a massive nuclear exchange between the superpowers could be summarized as "nuclear winter," with rapid temperature, precipitation, and insolation drops at the surface that would threaten global agriculture. The global nuclear arsenal has fallen by a factor of three since then, but there has been an expansion of the number of nuclear weapons states, with other states trying to develop nuclear arsenals. We use a modern climate model to re- examine the climate response to a range of nuclear wars, producing 5, 50, and 150 Tg of smoke, using tiny, moderate, and large portions of the global arsenal, and find that there would be significant climatic responses to all the scenarios. This is the first time that an atmosphere-ocean general circulation model has been used for such a simulation, and the first time that 10-yr simulations have been conducted. The response to the moderate and large scenarios can still be characterized as nuclear winter, with global catastrophic consequences, but the tiny scenario would still produce climate changes unprecedented in recorded human history. The changes are more long-lasting than previously thought, because the new model, NASA GISS ModelE, is able to represent the atmosphere up to 80 km, and simulates plume rise to the middle and upper stratosphere, producing a long aerosol lifetime. The indirect effects of the use of even a small number of nuclear weapons would have devastating consequences for the planet, and policy responses to the problem of nuclear proliferation need to take into account these environmental effects.

  7. Changes in intracellular calcium concentration influence beat-to-beat variability of action potential duration in canine ventricular myocytes.

    PubMed

    Kistamas, K; Szentandrassy, N; Hegyi, B; Vaczi, K; Ruzsnavszky, F; Horvath, B; Banyasz, T; Nanasi, P P; Magyar, J

    2015-02-01

    The aim of the present work was to study the influence of changes in intracellular calcium concentration ([Ca(2+)]i) on beat-to-beat variability (short term variability, SV) of action potential duration (APD) in isolated canine ventricular cardiomyocytes. Series of action potentials were recorded from enzymatically isolated canine ventricular cells using conventional microelectrode technique. Drug effects on SV were evaluated as relative SV changes determined by plotting the drug-induced changes in SV against corresponding changes in APD and comparing these data to the exponential SV-APD function obtained with inward and outward current injections. Exposure of myocytes to the Ca(2+) chelator BAPTA-AM (5 μM) decreased, while Ca(2+) ionophore A23187 (1 μM) increased the magnitude of relative SV. Both effects were primarily due to the concomitant changes in APD. Relative SV was reduced by BAPTA-AM under various experimental conditions including pretreatment with veratridine, BAY K8644, dofetilide or E-4031. Contribution of transient changes of [Ca(2+)]i due to Ca(2+) released from the sarcoplasmic reticulum (SR) was studied using 10 μM ryanodine and 1 μM cyclopiazonic acid: relative SV was reduced by both agents. Inhibition of the Na(+)-Ca(2+) exchanger by 1 μM SEA0400 increased relative SV. It is concluded that elevation of [Ca(2+)]i increases relative SV significantly. More importantly, Ca(2+) released from the SR is an important component of this effect. PMID:25716967

  8. Combined electric field and gap junctions on propagation of action potentials in cardiac muscle and smooth muscle in PSpice simulation.

    PubMed

    Sperelakis, Nicholas

    2003-10-01

    Propagation of action potentials in cardiac muscle and smooth muscle were simulated using the PSpice program. Excitation was transmitted from cell to cell along a strand of 6 cells (cardiac muscle) or 10 cells (smooth muscle) either not connected (control) or connected by low-resistance tunnels (gap-junction connexons). A significant negative cleft potential (V(jv) ) develops in the narrow junctional cleft when the pre-JM fires. V(jc) depolarizes the postjunctional membrane (post-JM) to threshold by a patch-clamp action. With few connecting tunnels, cell-to-cell transmission by the EF mechanism was facilitated. With many tunnels, propagation was dominated by the low-resistance mechanism, and propagation velocity (theta) became very fast and nonphysiological. In conclusion, when the 2 mechanisms for cell-to-cell transfer of excitation were combined, the two mechanisms facilitated each other in a synergistic manner. When there were many connecting tunnels, the tunnel mechanism was dominant. PMID:14661164

  9. An exploratory investigation of various modes of action and potential adverse outcomes of fluoxetine in marine mussels.

    PubMed

    Franzellitti, Silvia; Buratti, Sara; Capolupo, Marco; Du, Bowen; Haddad, Samuel P; Chambliss, C Kevin; Brooks, Bryan W; Fabbri, Elena

    2014-06-01

    The present study investigated possible adverse outcome pathways (AOPs) of the antidepressant fluoxetine (FX) in the marine mussel Mytilus galloprovincialis. An evaluation of molecular endpoints involved in modes of action (MOAs) of FX and biomarkers for sub-lethal toxicity were explored in mussels after a 7-day administration of nominal FX concentrations encompassing a range of environmentally relevant values (0.03-300ng/L). FX bioaccumulated in mussel tissues after treatment with 30 and 300ng/L FX, resulting in bioconcentration factor (BCF) values ranging from 200 to 800, which were higher than expected based solely on hydrophobic partitioning models. Because FX acts as a selective serotonin (5-HT) re-uptake inhibitor increasing serotonergic neurotransmission at mammalian synapses, cell signaling alterations triggered by 5-HT receptor occupations were assessed. cAMP levels and PKA activities were decreased in digestive gland and mantle/gonads of FX-treated mussels, consistent with an increased occupation of 5-HT1 receptors negatively coupled to the cAMP/PKA pathway. mRNA levels of a ABCB gene encoding the P-glycoprotein were also significantly down-regulated. This membrane transporter acts in detoxification towards xenobiotics and in altering pharmacokinetics of antidepressants; moreover, it is under a cAMP/PKA transcriptional regulation in mussels. Potential stress effects of FX were investigated using a battery of biomarkers for mussel health status that included lysosomal parameters, antioxidant enzyme activities, lipid peroxidation, and acetylcholinesterase activity. FX reduced the health status of mussels and induced lysosomal alterations, as suggested by reduction of lysosomal membrane stability in haemocytes and by lysosomal accumulation of neutral lipids in digestive gland. No clear antioxidant responses to FX were detected in digestive gland, while gills displayed significant increases of catalase and glutathione-s-transferase activities and a

  10. Use of Chemical Mixtures to Differentiate Mechanisms of Endocrine Action in a Small Fish Model

    EPA Science Inventory

    Various assays with adult fish have been developed to identify potential endocrine-disrupting chemicals (EDCs) which may cause toxicity via alterations in the hypothalamic-pituitary-gonadal (HPG) axis via different mechanisms/modes of action (MOA). These assays can be sensitive ...

  11. A wavelet-like filter based on neuron action potentials for analysis of human scalp electroencephalographs.

    PubMed

    Glassman, Elena L

    2005-11-01

    This paper describes the development and testing of a wavelet-like filter, named the SNAP, created from a neural activity simulation and used, in place of a wavelet, in a wavelet transform for improving EEG wavelet analysis, intended for brain-computer interfaces. The hypothesis is that an optimal wavelet can be approximated by deriving it from underlying components of the EEG. The SNAP was compared to standard wavelets by measuring Support Vector Machine-based EEG classification accuracy when using different wavelets/filters for EEG analysis. When classifying P300 evoked potentials, the error, as a function of the wavelet/filter used, ranged from 6.92% to 11.99%, almost twofold. Classification using the SNAP was more accurate than that with any of the six standard wavelets tested. Similarly, when differentiating between preparation for left- or right-hand movements, classification using the SNAP was more accurate (10.03% error) than for four out of five of the standard wavelets (9.54% to 12.00% error) and internationally competitive (7% error) on the 2001 NIPS competition test set. Phenomena shown only in maps of discriminatory EEG activity may explain why the SNAP appears to have promise for improving EEG wavelet analysis. It represents the initial exploration of a potential family of EEG-specific wavelets. PMID:16285389

  12. The sandwich model: the 'music and dance' of therapeutic action.

    PubMed

    Harrison, Alexandra M

    2014-04-01

    My premise is that a 'layered' approach is necessary to understand the process of exchanges that result in therapeutic change. I imagine these processes occurring in three layers - although the number of domains in which change is taking place is actually infinite - such as in a sandwich. The top layer, or top slice of bread of the sandwich, represents a broad view of the change process; it is non-linear and includes the feature of uncertainty, a general principle of dynamic systems theory. The middle layer, or the meat of the sandwich, is explained by theories that are immediately and clinically useful to a therapist, such as psychoanalytic theories. These are primarily linear theories and use language and symbols to 'tell a story of what happened'. The bottom layer, or bottom slice of bread of the sandwich, is the micro-process; this layer includes the moment-to-moment patterns of coordinated rhythms that both communicate meaning and provide the essential scaffold for all higher-level change processes. The micro-process also requires a non-linear theory to make sense of its variability and emergent properties. Taking a bite out of the sandwich will include a 'polysemic bundle of communicative behaviors' (Harrison and Tronick, 2011). I will illustrate the 'sandwich model' with the clinical case of the analytic treatment of a 5 year-old boy. PMID:24354856

  13. Two potential quark models for double heavy baryons

    NASA Astrophysics Data System (ADS)

    Puchkov, A. M.; Kozhedub, A. V.

    2016-01-01

    Baryons containing two heavy quarks (QQ' q) are treated in the Born-Oppenheimer approximation. Two non-relativistic potential models are proposed, in which the Schrödinger equation admits a separation of variables in prolate and oblate spheroidal coordinates, respectively. In the first model, the potential is equal to the sum of Coulomb potentials of the two heavy quarks, separated from each other by a distance - R and linear potential of confinement. In the second model the center distance parameter R is assumed to be purely imaginary. In this case, the potential is defined by the two-sheeted mapping with singularities being concentrated on a circle rather than at separate points. Thus, in the first model diquark appears as a segment, and in the second - as a circle. In this paper we calculate the mass spectrum of double heavy baryons in both models, and compare it with previous results.

  14. The developing cognitive substrate of sequential action control in 9- to 12-month-olds: evidence for concurrent activation models.

    PubMed

    Verschoor, S A; Paulus, M; Spapé, M; Biro, S; Hommel, B

    2015-05-01

    Nine-month-olds start to perform sequential actions. Yet, it remains largely unknown how they acquire and control such actions. We studied infants' sequential-action control by employing a novel gaze-contingent eye tracking paradigm. Infants experienced occulo-motor action sequences comprising two elementary actions. To contrast chaining, concurrent and integrated models of sequential-action control, we then selectively activated secondary actions to assess interactions with the primary actions. Behavioral and pupillometric results suggest 12-month-olds acquire sequential action without elaborate strategy through exploration. Furthermore, the inhibitory mechanisms ensuring ordered performance develop between 9 and 12 months of age, and are best captured by concurrent models. PMID:25704583

  15. The extracellular potential of a myelinated nerve fiber in an unbounded medium and in nerve cuff models.

    PubMed Central

    Struijk, J J

    1997-01-01

    A model is presented for the calculation of single myelinated fiber action potentials in an unbounded homogeneous medium and in nerve cuff electrodes. The model consists of a fiber model, used to calculate the action currents at the nodes of Ranvier, and a cylindrically symmetrical volume conductor model in which the fiber's nodes are represented as point current sources. The extracellular action potentials were shown to remain unchanged if the fiber diameter and the volume conductor geometry are scaled by the same factor (principle of corresponding states), both in an unbounded homogeneous medium and in an inhomogeneous volume conductor. The influence of several cuff electrode parameters, among others, cuff length and cuff diameter, were studied, and the results were compared, where possible, with theoretical and experimental results as reported in the literature. Images FIGURE 2 PMID:9168022

  16. Adjuvant potential of resiquimod with inactivated Newcastle disease vaccine and its mechanism of action in chicken.

    PubMed

    Sachan, Swati; Ramakrishnan, Saravanan; Annamalai, Arunsaravanakumar; Sharma, Bal Krishan; Malik, Hina; Saravanan, B C; Jain, Lata; Saxena, Meeta; Kumar, Ajay; Krishnaswamy, Narayanan

    2015-08-26

    Resiquimod (R-848), an imidazoquinoline compound, is a potent synthetic Toll-like receptor (TLR) 7 agonist. Although the solitary adjuvant potential of R-848 is well established in mammals, such reports are not available in avian species hitherto. Hence, the adjuvant potential of R-848 was tested in SPF chicken in this study. Two week old chicks were divided into four groups (10 birds/group) viz., control (A), inactivated Newcastle disease virus (NDV) vaccine prepared from velogenic strain (B), commercial oil adjuvanted inactivated NDV vaccine prepared from lentogenic strain (C) and inactivated NDV vaccine prepared from velogenic strain with R-848 (D). Booster was given two weeks post primary vaccination. Humoral immune response was assessed by haemagglutination inhibition (HI) test and ELISA while the cellular immune response was quantified by lymphocyte transformation test (LTT) and flow cytometry post-vaccination. Entire experiment was repeated twice to check the reproducibility. Highest HI titre was observed in group D at post booster weeks 1 and 2 that corresponds to mean log2 HI titre of 6.4 ± 0.16 and 6.8 ± 0.13, respectively. The response was significantly higher than that of group B or C (P<0.01). LTT stimulation index (P ≤ 0.01) as well as CD4(+) and CD8(+) cells in flow cytometry (P<0.05) were significantly high and maximum in group D. Group D conferred complete protection against virulent NDV challenge, while it was only 80% in group B and C. To understand the effects of R-848, the kinetics of immune response genes in spleen were analyzed using quantitative real-time PCR after R-848 administration (50 μg/bird, i.m. route). Resiquimod significantly up-regulated the expression of IFN-α, IFN-β, IFN-γ, IL-1β, IL-4, iNOS and MHC-II genes (P<0.01). In conclusion, the study demonstrated the adjuvant potential of R-848 when co-administered with inactivated NDV vaccine in SPF chicken which is likely due to the up-regulation of immune response genes

  17. Dipeptidyl Peptidase IV as a Potential Target for Selective Prodrug Activation and Chemotherapeutic Action in Cancers

    PubMed Central

    2015-01-01

    The efficacy of chemotherapeutic drugs is often offset by severe side effects attributable to poor selectivity and toxicity to normal cells. Recently, the enzyme dipeptidyl peptidase IV (DPPIV) was considered as a potential target for the delivery of chemotherapeutic drugs. The purpose of this study was to investigate the feasibility of targeting chemotherapeutic drugs to DPPIV as a strategy to enhance their specificity. The expression profile of DPPIV was obtained for seven cancer cell lines using DNA microarray data from the DTP database, and was validated by RT-PCR. A prodrug was then synthesized by linking the cytotoxic drug melphalan to a proline-glycine dipeptide moiety, followed by hydrolysis studies in the seven cell lines with a standard substrate, as well as the glycyl-prolyl-melphalan (GP-Mel). Lastly, cell proliferation studies were carried out to demonstrate enzyme-dependent activation of the candidate prodrug. The relative RT-PCR expression levels of DPPIV in the cancer cell lines exhibited linear correlation with U95Av2 Affymetrix data (r2 = 0.94), and with specific activity of a standard substrate, glycine-proline-p-nitroanilide (r2 = 0.96). The significantly higher antiproliferative activity of GP-Mel in Caco-2 cells (GI50 = 261 μM) compared to that in SK-MEL-5 cells (GI50 = 807 μM) was consistent with the 9-fold higher specific activity of the prodrug in Caco-2 cells (5.14 pmol/min/μg protein) compared to SK-MEL-5 cells (0.68 pmol/min/μg protein) and with DPPIV expression levels in these cells. Our results demonstrate the great potential to exploit DPPIV as a prodrug activating enzyme for efficient chemotherapeutic drug targeting. PMID:25365774

  18. Sustained Exocytosis after Action Potential-Like Stimulation at Low Frequencies in Mouse Chromaffin Cells Depends on a Dynamin-Dependent Fast Endocytotic Process

    PubMed Central

    Moya-Díaz, José; Álvarez, Yanina D.; Montenegro, Mauricio; Bayonés, Lucas; Belingheri, Ana V.; González-Jamett, Arlek M.; Cárdenas, Ana M.; Marengo, Fernando D.

    2016-01-01

    Under basal conditions the action potential firing rate of adrenal chromaffin cells is lower than 0.5 Hz. The maintenance of the secretory response at such frequencies requires a continuous replenishment of releasable vesicles. However, the mechanism that allows such vesicle replenishment remains unclear. Here, using membrane capacitance measurements on mouse chromaffin cells, we studied the mechanism of replenishment of a group of vesicles released by a single action potential-like stimulus (APls). The exocytosis triggered by APls (ETAP) represents a fraction (40%) of the immediately releasable pool, a group of vesicles highly coupled to voltage dependent calcium channels. ETAP was replenished with a time constant of 0.73 ± 0.11 s, fast enough to maintain synchronous exocytosis at 0.2–0.5 Hz stimulation. Regarding the mechanism involved in rapid ETAP replenishment, we found that it depends on the ready releasable pool; indeed depletion of this vesicle pool significantly delays ETAP replenishment. On the other hand, ETAP replenishment also correlates with a dynamin-dependent fast endocytosis process (τ = 0.53 ± 0.01 s). In this regard, disruption of dynamin function markedly inhibits the fast endocytosis and delays ETAP replenishment, but also significantly decreases the synchronous exocytosis during repetitive APls stimulation at low frequencies (0.2 and 0.5 Hz). Considering these findings, we propose a model in where both the transfer of vesicles from ready releasable pool and fast endocytosis allow rapid ETAP replenishment during low stimulation frequencies. PMID:27507935

  19. Sustained Exocytosis after Action Potential-Like Stimulation at Low Frequencies in Mouse Chromaffin Cells Depends on a Dynamin-Dependent Fast Endocytotic Process.

    PubMed

    Moya-Díaz, José; Álvarez, Yanina D; Montenegro, Mauricio; Bayonés, Lucas; Belingheri, Ana V; González-Jamett, Arlek M; Cárdenas, Ana M; Marengo, Fernando D

    2016-01-01

    Under basal conditions the action potential firing rate of adrenal chromaffin cells is lower than 0.5 Hz. The maintenance of the secretory response at such frequencies requires a continuous replenishment of releasable vesicles. However, the mechanism that allows such vesicle replenishment remains unclear. Here, using membrane capacitance measurements on mouse chromaffin cells, we studied the mechanism of replenishment of a group of vesicles released by a single action potential-like stimulus (APls). The exocytosis triggered by APls (ETAP) represents a fraction (40%) of the immediately releasable pool, a group of vesicles highly coupled to voltage dependent calcium channels. ETAP was replenished with a time constant of 0.73 ± 0.11 s, fast enough to maintain synchronous exocytosis at 0.2-0.5 Hz stimulation. Regarding the mechanism involved in rapid ETAP replenishment, we found that it depends on the ready releasable pool; indeed depletion of this vesicle pool significantly delays ETAP replenishment. On the other hand, ETAP replenishment also correlates with a dynamin-dependent fast endocytosis process (τ = 0.53 ± 0.01 s). In this regard, disruption of dynamin function markedly inhibits the fast endocytosis and delays ETAP replenishment, but also significantly decreases the synchronous exocytosis during repetitive APls stimulation at low frequencies (0.2 and 0.5 Hz). Considering these findings, we propose a model in where both the transfer of vesicles from ready releasable pool and fast endocytosis allow rapid ETAP replenishment during low stimulation frequencies. PMID:27507935

  20. The Things You Do: Internal Models of Others’ Expected Behaviour Guide Action Observation

    PubMed Central

    Schenke, Kimberley C.; Wyer, Natalie A.; Bach, Patric

    2016-01-01

    Predictions allow humans to manage uncertainties within social interactions. Here, we investigate how explicit and implicit person models–how different people behave in different situations–shape these predictions. In a novel action identification task, participants judged whether actors interacted with or withdrew from objects. In two experiments, we manipulated, unbeknownst to participants, the two actors action likelihoods across situations, such that one actor typically interacted with one object and withdrew from the other, while the other actor showed the opposite behaviour. In Experiment 2, participants additionally received explicit information about the two individuals that either matched or mismatched their actual behaviours. The data revealed direct but dissociable effects of both kinds of person information on action identification. Implicit action likelihoods affected response times, speeding up the identification of typical relative to atypical actions, irrespective of the explicit knowledge about the individual’s behaviour. Explicit person knowledge, in contrast, affected error rates, causing participants to respond according to expectations instead of observed behaviour, even when they were aware that the explicit information might not be valid. Together, the data show that internal models of others’ behaviour are routinely re-activated during action observation. They provide first evidence of a person-specific social anticipation system, which predicts forthcoming actions from both explicit information and an individuals’ prior behaviour in a situation. These data link action observation to recent models of predictive coding in the non-social domain where similar dissociations between implicit effects on stimulus identification and explicit behavioural wagers have been reported. PMID:27434265

  1. K+ accumulation and K+ conductance inactivation during action potential trains in giant axons of the squid Sepioteuthis.

    PubMed Central

    Inoue, I; Tsutsui, I; Brown, E R

    1997-01-01

    1. During action potential trains in giant axons from the squid Sepioteuthis, decline of the peak level of the undershoot potential was observed. The time course of the decline of the undershoot could be fitted with a three-exponential function with time constants of approximately 25, approximately 400 and approximately 7,000 ms, respectively. 2. When the osmolarity of the external solution was doubled by adding glucose (1.2 M), the fast component of undershoot decline, but not the medium and slow components, was significantly reduced. 3. Under voltage clamp in high osmolarity solutions where K+ accumulation was completely removed, repeated depolarizing pulses at 40 Hz (designed to mimic a train of action potentials) elicited K+ currents whose peak value declined. The decline is consistent with inactivation of the K+ conductance (gK). The decline of gK was fitted by a two-exponential function with time constants of approximately 400 and approximately 7,000 ms, respectively. 4. Interventions designed to modify Schwann cell physiology, such as high frequency stimulation (100 Hz, 2 min), externally applied ouabain (100-500 microM), L-glutamate (100 microM), ACh (100 microM), Co2+ (5mM), Ba2+ (2mM), or removal of external Ca2+ by EGTA, had no significant effects on the fast, medium or slow components of undershoot decline. 5. The results suggest that the fast component of undershoot decline represents K+ accumulation in the space between Schwann cell and axolemma. The medium and slow components are the result of axonal gK inactivation. Schwann cells appear to be involved in K+ clearance only to the extent that they provide an efficient physical pathway for the clearance of K+ by extracellular diffusion. PMID:9147323

  2. Big data to smart data in Alzheimer's disease: The brain health modeling initiative to foster actionable knowledge.

    PubMed

    Geerts, Hugo; Dacks, Penny A; Devanarayan, Viswanath; Haas, Magali; Khachaturian, Zaven S; Gordon, Mark Forrest; Maudsley, Stuart; Romero, Klaus; Stephenson, Diane

    2016-09-01

    Massive investment and technological advances in the collection of extensive and longitudinal information on thousands of Alzheimer patients results in large amounts of data. These "big-data" databases can potentially advance CNS research and drug development. However, although necessary, they are not sufficient, and we posit that they must be matched with analytical methods that go beyond retrospective data-driven associations with various clinical phenotypes. Although these empirically derived associations can generate novel and useful hypotheses, they need to be organically integrated in a quantitative understanding of the pathology that can be actionable for drug discovery and development. We argue that mechanism-based modeling and simulation approaches, where existing domain knowledge is formally integrated using complexity science and quantitative systems pharmacology can be combined with data-driven analytics to generate predictive actionable knowledge for drug discovery programs, target validation, and optimization of clinical development. PMID:27238630

  3. Documentation of a Model Action Plan to Deter Illicit Nuclear Trafficking

    SciTech Connect

    Smith, D; Kristo, M; Niemeyer, S; Dudder, G

    2006-07-28

    Theft, illegal possession, smuggling, or attempted unauthorized sale of nuclear and radiological materials remains a worldwide problem. The Nuclear Smuggling International Technical Working Group (ITWG) has adopted a model action plan to guide investigation of these cases through a systematic approach to nuclear forensics. The model action plan was recently documented and provides recommendations concerning incident response, collection of evidence in conformance with required legal standards, laboratory sampling and distribution of samples, radioactive materials analysis, including categorization and characterization of samples, forensics analysis of conventional evidence, and case development including interpretation of forensic signatures.

  4. Documentation of a model action plan to deter illicit nuclear trafficking

    SciTech Connect

    Smith, D. K.; Kristo, M. J.; Niemeyer, S.; Dudder, Gordon B.

    2008-05-04

    Theft, illegal possession, smuggling, or attempted unathorized sale of nuclear and radiological materials remains a worldwide problem. The Nuclear Smuggling International Technical Working Group (ITWG) has adopted a model action plan to guide investigation of these cases through a systematic approach to nuclear forensics. The