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Sample records for action potentials generated

  1. 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

  2. Modeling of action potential generation in NG108-15 cells.

    PubMed

    Molnar, Peter; Hickman, James J

    2014-01-01

    In order to explore the possibility of identifying toxins based on their effect on the shape of action potentials, we created a computer model of the action potential generation in NG108-15 cells (a neuroblastoma/glioma hybrid cell line). To generate the experimental data for model validation, voltage-dependent sodium, potassium and high-threshold calcium currents, as well as action potentials, were recorded from NG108-15 cells with conventional whole-cell patch-clamp methods. Based on the classic Hodgkin-Huxley formalism and the linear thermodynamic description of the rate constants, ion-channel parameters were estimated using an automatic fitting method. Utilizing the established parameters, action potentials were generated using the Hodgkin-Huxley formalism and were fitted to the recorded action potentials. To demonstrate the applicability of the method for toxin detection and discrimination, the effect of tetrodotoxin (a sodium channel blocker) and tefluthrin (a pyrethroid that is a sodium channel opener) were studied. The two toxins affected the shape of the action potentials differently, and their respective effects were identified based on the predicted changes in the fitted parameters.

  3. Ca2+ involvement in the action potential generation of myenteric neurones in the rat oesophagus.

    PubMed

    De Laet, A; Cornelissen, W; Adriaensen, D; Van Bogaert, P-P; Scheuermann, D W; Timmermans, J-P

    2002-04-01

    Intracellular recordings were used to study the physiological behaviour of rat oesophageal myenteric neurones, which are embedded in striated muscle. Injection of depolarizing pulses evoked action potentials with a clear 'shoulder' in all neurones. This shoulder disappeared under low Ca2+/high Mg2+ conditions. Tetrodotoxin (TTX; 1 micromol L-1) did not impede spike firing, whereas under combined TTX and low Ca2+/high Mg2+ conditions the action potentials were completely abolished, indicating that TTX- resistant action potentials are mediated by a Ca2+ current. Further experiments with omega-conotoxin GVIA (100 nmol L-1) revealed that these Ca2+ currents enter the cell via N-type voltage-activated Ca2+ channels (see also accompanying paper). Tetraethylammonium (10 mmol L-1) caused broadening of the action potentials, which probably resulted from prolonged Ca2+ influx due to blockade of the delayed rectifier K+ channel. Although Ca2+ appears to be involved in the spike generation of all rat oesophageal myenteric neurones, only a minority (14%) shows a slow afterhyperpolarization. Thus, no strict correlation exists between the presence of a shoulder and a slow afterhyperpolarization. Furthermore, morphological identification of 25 of the impaled neurones revealed that there was no strict correlation between morphology and electrophysiological behaviour. Consequently, rat oesophageal myenteric neurones appear to differ in several aspects from myenteric neurones in smooth muscle regions of the gastrointestinal tract.

  4. Computer Simulations Support a Morphological Contribution to BDNF Enhancement of Action Potential Generation

    PubMed Central

    Hiester, Brian G.; Jones, Kevin R.

    2016-01-01

    Brain-derived neurotrophic factor (BDNF) regulates both action potential (AP) generation and neuron morphology. However, whether BDNF-induced changes in neuron morphology directly impact AP generation is unclear. We quantified BDNF’s effect on cultured cortical neuron morphological parameters and found that BDNF stimulates dendrite growth and addition of dendrites while increasing both excitatory and inhibitory presynaptic inputs in a spatially restricted manner. To gain insight into how these combined changes in neuron structure and synaptic input impact AP generation, we used the morphological parameters we gathered to generate computational models. Simulations suggest that BDNF-induced neuron morphologies generate more APs under a wide variety of conditions. Synapse and dendrite addition have the greatest impact on AP generation. However, subtle alterations in excitatory/inhibitory synapse ratio and strength have a significant impact on AP generation when synaptic activity is low. Consistent with these simulations, BDNF rapidly enhances spontaneous activity in cortical cultures. We propose that BDNF promotes neuron morphologies that are intrinsically more efficient at translating barrages of synaptic activity into APs, which is a previously unexplored aspect of BDNF’s function. PMID:27683544

  5. Evidence that the compound action potential (CAP) from the auditory nerve is a stationary potential generated across dura mater.

    PubMed

    Brown, Daniel J; Patuzzi, Robert B

    2010-08-01

    We have investigated the generation of the compound action potential (CAP) from the auditory nerve of guinea pigs. Responses to acoustic tone-bursts were recorded from the round window (RW), throughout the cochlear fluids, from the surface of the cochlear nucleus, from the central end of the auditory nerve after removal of the cochlear nucleus, from the scalp vertex, and from the contralateral ear. Responses were compared before, during and after experimental manipulations including pharmacological blockade of the auditory nerve, section of the auditory nerve, section of the efferent nerves, removal of the cochlear nucleus, and focal cooling of the cochlear nerve and/or cochlear nucleus. Regardless of the waveform changes occurring with these manipulations, the responses were similar in waveform but inverted polarity across the internal auditory meatus. The CAP waveforms were very similar before and after removal of the cochlear nucleus, apart from transient changes that could last many minutes. This suggests that the main CAP components are generated entirely by the eighth nerve. Based on previous studies and a clear understanding of the generation of extracellular potentials, we suggest that the early components in the responses recorded from the round window, from the cochlear fluids, from the surface of the cochlear nucleus, or from the scalp are a far-field or stationary potential, generated when the circulating action currents associated with each auditory neurone encounters a high extracellular resistance as it passes through the dura mater.

  6. Pattern-dependent Role of NMDA receptors in Action Potential Generation: Consequences on ERK Activation

    PubMed Central

    Zhao, Meilan; Adams, J. Paige

    2005-01-01

    Synaptic long-term potentiation is maintained through gene transcription, but how the nucleus is recruited remains controversial. Activation of extracellular-signal regulated kinases 1 and 2 (ERKs) with synaptic stimulation has been shown to require NMDA receptors (NMDARs), yet stimulation intensities sufficient to recruit action potentials (APs) also appear to be required. This has led us to ask the question whether NMDARs are necessary for AP generation as they relate to ERK activation. To test this, we examined the effects of NMDAR blockade on APs induced with synaptic stimulation using whole-cell current clamp recordings from CA1 pyramidal cells in hippocampal slices. NMDAR antagonists were found to potently inhibit APs generated with 5 and 100 Hz synaptic stimulation. Blockade of APs, and ERK activation, could be overcome with the addition of the GABA-A antagonist bicuculline, indicating that APs are sufficient to activate signals such as ERK in the nucleus and throughout the neuron in the continued presence of NMDAR antagonists. Interestingly, no effects of the NMDAR antagonists were observed when theta-burst stimulation (TBS) was used. This resistance to the antagonists is conferred by temporal summation during the bursts. These results clarify findings from a previous study showing that ERK activation induced with TBS is resistant to APV, in contrast to that induced with 5 Hz or 100 Hz stimulation, which is sensitive. By showing that NMDAR blockade inhibits AP generation, we demonstrate that a major role NMDARs play in cell-wide and nuclear ERK activation is through their contribution to action potential generation. PMID:16049179

  7. 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

    2014-04-09

    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.

  8. Encoding of High Frequencies Improves with Maturation of Action Potential Generation in Cultured Neocortical Neurons

    PubMed Central

    Nikitin, Evgeny S.; Bal, Natalia V.; Malyshev, Aleksey; Ierusalimsky, Victor N.; Spivak, Yulia; Balaban, Pavel M.; Volgushev, Maxim

    2017-01-01

    The ability of neocortical neurons to detect and encode rapid changes at their inputs is crucial for basic neuronal computations, such as coincidence detection, precise synchronization of activity and spike-timing dependent plasticity. Indeed, populations of cortical neurons can respond to subtle changes of the input very fast, on a millisecond time scale. Theoretical studies and model simulations linked the encoding abilities of neuronal populations to the fast onset dynamics of action potentials (APs). Experimental results support this idea, however mechanisms of fast onset of APs in cortical neurons remain elusive. Studies in neuronal cultures, that are allowing for accurate control over conditions of growth and microenvironment during the development of neurons and provide better access to the spike initiation zone, may help to shed light on mechanisms of AP generation and encoding. Here we characterize properties of AP encoding in neocortical neurons grown for 11–25 days in culture. We show that encoding of high frequencies improves upon culture maturation, which is accompanied by the development of passive electrophysiological properties and AP generation. The onset of APs becomes faster with culture maturation. Statistical analysis using correlations and linear model approaches identified the onset dynamics of APs as a major predictor of age-dependent changes of encoding. Encoding of high frequencies strongly correlated also with the input resistance of neurons. Finally, we show that maturation of encoding properties of neurons in cultures is similar to the maturation of encoding in neurons studied in slices. These results show that maturation of AP generators and encoding is, to a large extent, determined genetically and takes place even without normal micro-environment and activity of the whole brain in vivo. This establishes neuronal cultures as a valid experimental model for studying mechanisms of AP generation and encoding, and their maturation. PMID

  9. 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

  10. 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.

  11. Pattern-dependent role of NMDA receptors in action potential generation: consequences on extracellular signal-regulated kinase activation.

    PubMed

    Zhao, Meilan; Adams, J Paige; Dudek, Serena M

    2005-07-27

    Synaptic long-term potentiation is maintained through gene transcription, but how the nucleus is recruited remains controversial. Activation of extracellular signal-regulated kinases (ERKs) 1 and 2 with synaptic stimulation has been shown to require NMDA receptors (NMDARs), yet stimulation intensities sufficient to recruit action potentials (APs) also appear to be required. This has led us to ask the question of whether NMDARs are necessary for AP generation as they relate to ERK activation. To test this, we examined the effects of NMDAR blockade on APs induced with synaptic stimulation using whole-cell current-clamp recordings from CA1 pyramidal cells in hippocampal slices. NMDAR antagonists were found to potently inhibit APs generated with 5 and 100 Hz synaptic stimulation. Blockade of APs and ERK activation could be overcome with the addition of the GABAA antagonist bicuculline, indicating that APs are sufficient to activate signals such as ERK in the nucleus and throughout the neuron in the continued presence of NMDAR antagonists. Interestingly, no effects of the NMDAR antagonists were observed when theta-burst stimulation (TBS) was used. This resistance to the antagonists is conferred by temporal summation during the bursts. These results clarify findings from a previous study showing that ERK activation induced with TBS is resistant to 2-amino-5-phosphonovalerate, in contrast to that induced with 5 or 100 Hz stimulation, which is sensitive. By showing that NMDAR blockade inhibits AP generation, we demonstrate that a major role that NMDARs play in cell-wide and nuclear ERK activation is through their contribution to action potential generation.

  12. Next-generation sequencing identifies high frequency of mutations in potentially clinically actionable genes in sebaceous carcinoma.

    PubMed

    Tetzlaff, Michael T; Singh, Rajesh R; Seviour, Elena G; Curry, Jonathan L; Hudgens, Courtney W; Bell, Diana; Wimmer, Daniel A; Ning, Jing; Czerniak, Bogdan A; Zhang, Li; Davies, Michael A; Prieto, Victor G; Broaddus, Russell R; Ram, Prahlad; Luthra, Rajyalakshmi; Esmaeli, Bita

    2016-09-01

    Sebaceous carcinoma (SC) is a rare but aggressive malignancy with frequent recurrence and metastases. Surgery is the mainstay of therapy, but effective systemic therapies are lacking because the molecular alterations driving SC remain poorly understood. To identify these, we performed whole-exome next-generation sequencing of 409 cancer-associated genes on 27 SCs (18 primary/locally recurrent ocular, 5 paired metastatic ocular, and 4 primary extraocular) from 20 patients. In ocular SC, we identified 139 non-synonymous somatic mutations (median/lesion 3; range 0-23). Twenty-five of 139 mutations (18%) occurred in potentially clinically actionable genes in 6 of 16 patients. The most common mutations were mutations in TP53 (n = 9), RB1 (n = 6), PIK3CA (n = 2), PTEN (n = 2), ERBB2 (n = 2), and NF1 (n = 2). TP53 and RB1 mutations were restricted to ocular SC and correlated with aberrant TP53 and RB protein expression. Systematic pathway analyses demonstrated convergence of these mutations to activation of the PI3K signalling cascade, and PI3K pathway activation was confirmed in tumours with PTEN and/or PIK3CA mutations. Considerable inter-tumoural heterogeneity was observed between paired primary and metastatic ocular SCs. In primary extraocular SC, we identified 77 non-synonymous somatic mutations (median/lesion 22.5; range 3-29). This overall higher mutational load was attributed to a microsatellite instability phenotype in three of four patients and somatically acquired mutations in mismatch repair genes in two of four patients. Eighteen of 77 mutations (23%) were in potentially clinically actionable genes in three of four patients, including BTK, FGFR2, PDGFRB, HRAS, and NF1 mutations. Identification of potentially clinically actionable mutations in 9 of 20 SC patients (45%) underscores the importance of next-generation sequencing to expand the spectrum of genotype-matched targeted therapies. Frequent activation of PI3K signalling pathways provides a strong

  13. Microparticles generated by decompression stress cause central nervous system injury manifested as neurohypophysial terminal action potential broadening.

    PubMed

    Yang, Ming; Kosterin, Paul; Salzberg, Brian M; Milovanova, Tatyana N; Bhopale, Veena M; Thom, Stephen R

    2013-11-01

    The study goal was to use membrane voltage changes during neurohypophysial action potential (AP) propagation as an index of nerve function to evaluate the role that circulating microparticles (MPs) play in causing central nervous system injury in response to decompression stress in a murine model. Mice studied 1 h following decompression from 790 kPa air pressure for 2 h exhibit a 45% broadening of the neurohypophysial AP. Broadening did not occur if mice were injected with the MP lytic agent polyethylene glycol telomere B immediately after decompression, were rendered thrombocytopenic, or were treated with an inhibitor of nitric oxide synthase-2 (iNOS) prior to decompression, or in knockout (KO) mice lacking myeloperoxidase or iNOS. If MPs were harvested from control (no decompression) mice and injected into naive mice, no AP broadening occurred, but AP broadening was observed with injections of equal numbers of MPs from either wild-type or iNOS KO mice subjected to decompression stress. Although not required for AP broadening, MPs from decompressed mice, but not control mice, exhibit NADPH oxidase activation. We conclude that inherent differences in MPs from decompressed mice, rather than elevated MPs numbers, mediate neurological injury and that a component of the perivascular response to MPs involves iNOS. Additional study is needed to determine the mechanism of AP broadening and also mechanisms for MP generation associated with exposure to elevated gas pressure.

  14. Kv3 potassium conductance is necessary and kinetically optimized for high-frequency action potential generation in hippocampal interneurons.

    PubMed

    Lien, Cheng-Chang; Jonas, Peter

    2003-03-15

    Kv3 channels are thought to be essential for the fast-spiking (FS) phenotype in GABAergic interneurons, but how these channels confer the ability to generate action potentials (APs) at high frequency is unknown. To address this question, we developed a fast dynamic-clamp system (approximately 50 kHz) that allowed us to add a Kv3 model conductance to CA1 oriens alveus (OA) interneurons in hippocampal slices. Selective pharmacological block of Kv3 channels by 0.3 mm 4-aminopyridine or 1 mm tetraethylammonium ions led to a marked broadening of APs during trains of short stimuli and a reduction in AP frequency during 1 sec stimuli. The addition of artificial Kv3 conductance restored the original AP pattern. Subtraction of Kv3 conductance by dynamic clamp mimicked the effects of the blockers. Application of artificial Kv3 conductance also led to FS in OA interneurons after complete K+ channel block and even induced FS in hippocampal pyramidal neurons in the absence of blockers. Adding artificial Kv3 conductance with altered deactivation kinetics revealed a nonmonotonic relationship between mean AP frequency and deactivation rate, with a maximum slightly above the original value. Insertion of artificial Kv3 conductance with either lowered activation threshold or inactivation also led to a reduction in the mean AP frequency. However, the mechanisms were distinct. Shifting the activation threshold induced adaptation, whereas adding inactivation caused frequency-dependent AP broadening. In conclusion, Kv3 channels are necessary for the FS phenotype of OA interneurons, and several of their gating properties appear to be optimized for high-frequency repetitive activity.

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

    NASA Astrophysics Data System (ADS)

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

    2013-06-01

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

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

    PubMed

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

    2013-07-21

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

  17. Imaging action potentials with calcium indicators.

    PubMed

    MacLean, Jason N; Yuste, Rafael

    2009-11-01

    The understanding of neuronal circuits has been, and will continue to be, greatly advanced by the simultaneous imaging of action potentials in neuronal ensembles. This protocol describes "bulk" loading of brain slices with acetoxymethyl (AM) ester calcium indicators in order to monitor action potential activity in large populations of neurons simultaneously. The imaging of calcium influx into neurons provides an indirect, but accurate, measure of action potential generation in individual neurons. Single-cell resolution, and thus the easy identification of every active cell, is the key advantage of the technique.

  18. Simulation of action potential propagation in plants.

    PubMed

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

    2011-12-21

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

  19. Chloride conducting light activated channel GtACR2 can produce both cessation of firing and generation of action potentials in cortical neurons in response to light.

    PubMed

    Malyshev, A Y; Roshchin, M V; Smirnova, G R; Dolgikh, D A; Balaban, P M; Ostrovsky, M A

    2017-02-15

    Optogenetics is a powerful technique in neuroscience that provided a great success in studying the brain functions during the last decade. Progress of optogenetics crucially depends on development of new molecular tools. Light-activated cation-conducting channelrhodopsin2 was widely used for excitation of cells since the emergence of optogenetics. In 2015 a family of natural light activated chloride channels GtACR was identified which appeared to be a very promising tool for using in optogenetics experiments as a cell silencer. Here we examined properties of GtACR2 channel expressed in the rat layer 2/3 pyramidal neurons by means of in utero electroporation. We have found that despite strong inhibition the light stimulation of GtACR2-positive neurons can surprisingly lead to generation of action potentials, presumably initiated in the axonal terminals. Thus, when using the GtACR2 in optogenetics experiments, its ability to induce action potentials should be taken into account. Our results also open an interesting possibility of using the GtACR2 both as cell silencer and cell activator in the same experiment varying the pattern of light stimulation.

  20. The action potential of Dionaea muscipula Ellis.

    PubMed

    Hodick, D; Sievers, A

    1988-04-01

    The intention of this investigation was to acquire more concise information about the nature of the action potential of Dionaea muscipula Ellis and the different types of cells generating and conducting it. It is shown by microelectrode measurements that, besides the sensory cells, all the major tissues of the trap lobes are excitable, firing action potentials with pronounced after-hyperpolarizations. The action potentials are strictly dependent on Ca(2+). Their peak depolarizations are shifted 25-27 mV in a positive direction after a tenfold increase in external Ca(2+) concentration. Perfusions with 1 mM ethylene glycol-bis(β-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) or 1 mM LaCl3 completely inhibit excitability. Magnesium ions only slightly affect the peak depolarizations but considerably prolong action potentials. Sodium azide and 2,4-dinitrophenol also abolish excitation, probably by reducing the intracellular ATP concentration. Furthermore, it is tested whether the sensory cells can be distinguished from the other cells of the trap by their electrical behaviour. The resting potentials of sensory cells (-161±7 mV) and mesophyll cells (-155±8 mV) are of the same magnitude. Changes in external ion concentrations affect resting and action potentials in both cell types in a similar way. Additional freeze-fracture studies of both cell types reveal similar numbers and distributions of intramembrane particles on the fracture faces of the plasma membrane, which is most likely the mechanosensor. These findings stress the view that the high mechanosensitivity of the sensory hair results from its anatomy and not from a specialized perception mechanism. It is proposed that trap closure is triggered by a rise in the cytoplasmic concentration of Ca(2+) or a Ca(2+)-activated regulatory complex, which must exceed a threshold concentration. Since the Ca(2+) influx during a single action potential does not suffice to reach this threshold, at least two stimulations

  1. Action Potential Initiation in Neocortical Inhibitory Interneurons

    PubMed Central

    Li, Tun; Tian, Cuiping; Scalmani, Paolo; Frassoni, Carolina; Mantegazza, Massimo; Wang, Yonghong; Yang, Mingpo; Wu, Si; Shu, Yousheng

    2014-01-01

    Action potential (AP) generation in inhibitory interneurons is critical for cortical excitation-inhibition balance and information processing. However, it remains unclear what determines AP initiation in different interneurons. We focused on two predominant interneuron types in neocortex: parvalbumin (PV)- and somatostatin (SST)-expressing neurons. Patch-clamp recording from mouse prefrontal cortical slices showed that axonal but not somatic Na+ channels exhibit different voltage-dependent properties. The minimal activation voltage of axonal channels in SST was substantially higher (∼7 mV) than in PV cells, consistent with differences in AP thresholds. A more mixed distribution of high- and low-threshold channel subtypes at the axon initial segment (AIS) of SST cells may lead to these differences. Surprisingly, NaV1.2 was found accumulated at AIS of SST but not PV cells; reducing NaV1.2-mediated currents in interneurons promoted recurrent network activity. Together, our results reveal the molecular identity of axonal Na+ channels in interneurons and their contribution to AP generation and regulation of network activity. PMID:25203314

  2. Computer Simulation of the Neuronal Action Potential.

    ERIC Educational Resources Information Center

    Solomon, Paul R.; And Others

    1988-01-01

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

  3. 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…

  4. Distributed Generation to Support Development-Focused Climate Action

    SciTech Connect

    Cox, Sadie; Gagnon, Pieter; Stout, Sherry; Zinaman, Owen; Watson, Andrea; Hotchkiss, Eliza

    2016-09-01

    This paper explores the role of distributed generation, with a high renewable energy contribution, in supporting low emission climate-resilient development. The paper presents potential impacts on development (via energy access), greenhouse gas emission mitigation, and climate resilience directly associated with distributed generation, as well as specific actions that may enhance or increase the likelihood of climate and development benefits. This paper also seeks to provide practical and timely insights to support distributed generation policymaking and planning within the context of common climate and development goals as the distributed generation landscape rapidly evolves globally. Country-specific distributed generation policy and program examples, as well as analytical tools that can inform efforts internationally, are also highlighted throughout the paper.

  5. Conscious awareness of action potentiates sensorimotor learning.

    PubMed

    Boutin, Arnaud; Blandin, Yannick; Massen, Cristina; Heuer, Herbert; Badets, Arnaud

    2014-10-01

    Many everyday skills are unconsciously learned through repetitions of the same behaviour by binding independent motor acts into unified sets of actions. However, our ability to be consciously aware of producing newly and highly trained motor skills raises the question of the role played by conscious awareness of action upon skill acquisition. In this study we strengthened conscious awareness of self-produced sequential finger movements by way of asking participants to judge their performance in terms of maximal fluency after each trial. Control conditions in which participants did not make any judgment or performance-unrelated judgments were also included. Findings indicate that conscious awareness of action, enhanced via subjective appraisal of motor efficiency, potentiates sensorimotor learning and skilful motor production in optimising the processing and sequencing of action units, as compared to the control groups. The current work lends support to the claim that the learning and skilful expression of sensorimotor behaviours might be grounded upon our ability to be consciously aware of our own motor capability and efficiency.

  6. Weber potential from finite velocity of action?

    NASA Astrophysics Data System (ADS)

    Wesley, J. P.

    1992-12-01

    The Weber potential energy U for charges q and q' separated by the distance R is U = (qq'/R)[1 - (dR/dt)2/2c2]. If this potential arises from a finite velocity c of energy transfer Q', where the retarded rate of transfer from q' to q is dQ(t-R/c)/dt = Q'[1 - (dR/dt)/c] and where the advanced rate from q to q' is dQ(t+R/c)/dt = Q'[1 + (dR/dt)/c], then the resultant time-average root-mean-square action is given by{{Q'}}sqrt {1 - {{({{{{{dR}}} {{{dt}}}}} )^2} {{{c}}^{{2}} }}} ≈ {{Q'}}[ {{{1 - }}{{( {{{{{dR}}} {{{dt}}}}} )^2 {{{{dR}}} {{{dt}}}}})^2 {2{{c}}^{{2}} }}}]. Identifying Q' with the Coulomb potential energy qq'/R, the Weber potential is obtained. Using the same argument, Newtonian gravitation yields a corresponding Weber potential energy, qq'/R being replaced by ( - Gmm'/R).

  7. The Characteristics of Action Potentials in Primo Vessels and the Effects of Acetylcholine Injection to the Action Potentials

    PubMed Central

    Cho, Seong Jin; Lim, Jaekwan; Yeon, Sun Hee; Kwon, O. Sang; Choi, Kwang-Ho; Choi, Sun-Mi; Ryu, Yeon-Hee

    2013-01-01

    In a previous study, we found that Primo vessels generate different action potentials in smooth muscles, but this study compared the pulse shape to distinguish the two tissues. Thus, a more sophisticated extracellular experiment was performed in this study using an acetylcholine injection; we then observed changes in the amplitude, FWHM (full width at half maximum), and period to explore Primo vessel function. A third type of pulse was recorded for Primo vessels. We observed fast depolarizing and repolarizing phases for this pulse. Further, its FWHM was 30 ms between smooth muscles and neurons. Acetylcholine affected only the period. The amplitude and FWHM were consistent after injection. Primo-vessels generated action potentials at twice the frequency after injection. From the results, we speculate that Primo-vessels perform a role in transferring signals in a different manner, which may be relevant for acupuncture treatment. PMID:23861710

  8. Action-potential modulation during axonal conduction.

    PubMed

    Sasaki, Takuya; Matsuki, Norio; Ikegaya, Yuji

    2011-02-04

    Once initiated near the soma, an action potential (AP) is thought to propagate autoregeneratively and distribute uniformly over axonal arbors. We challenge this classic view by showing that APs are subject to waveform modulation while they travel down axons. Using fluorescent patch-clamp pipettes, we recorded APs from axon branches of hippocampal CA3 pyramidal neurons ex vivo. The waveforms of axonal APs increased in width in response to the local application of glutamate and an adenosine A(1) receptor antagonist to the axon shafts, but not to other unrelated axon branches. Uncaging of calcium in periaxonal astrocytes caused AP broadening through ionotropic glutamate receptor activation. The broadened APs triggered larger calcium elevations in presynaptic boutons and facilitated synaptic transmission to postsynaptic neurons. This local AP modification may enable axonal computation through the geometry of axon wiring.

  9. Sodium action potentials in the dendrites of cerebellar Purkinje cells.

    PubMed

    Regehr, W G; Konnerth, A; Armstrong, C M

    1992-06-15

    We report here that in cerebellar Purkinje cells from which the axon has been removed, positive voltage steps applied to the voltage-clamped soma produce spikes of active current. The spikes are inward, are all-or-none, have a duration of approximately 1 ms, and are reversibly eliminated by tetrodotoxin, a Na channel poison. From cell to cell, the amplitude of the spikes ranges from 4 to 20 nA. Spike latency decreases as the depolarizing step is made larger. These spikes clearly arise at a site where the voltage is not controlled, remote from the soma. From these facts we conclude that Purkinje cell dendrites contain a sufficient density of Na channels to generate action potentials. Activation by either parallel fiber or climbing fiber synapses produces similar spikes, suggesting that normal input elicits Na action potentials in the dendrites. These findings greatly alter current views of how dendrites in these cells respond to synaptic input.

  10. 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

  11. 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

  12. 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.

  13. Action potential broadening in a presynaptic channelopathy.

    PubMed

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

    2016-07-06

    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.

  14. Warm body temperature facilitates energy efficient cortical action potentials.

    PubMed

    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.

  15. 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

  16. Investigating conceptions of intentional action by analyzing participant generated scenarios

    PubMed Central

    Skulmowski, Alexander; Bunge, Andreas; Cohen, Bret R.; Kreilkamp, Barbara A. K.; Troxler, Nicole

    2015-01-01

    We describe and report on results of employing a new method for analyzing lay conceptions of intentional and unintentional action. Instead of asking people for their conceptual intuitions with regard to construed scenarios, we asked our participants to come up with their own scenarios and to explain why these are examples of intentional or unintentional actions. By way of content analysis, we extracted contexts and components that people associated with these action types. Our participants associated unintentional actions predominantly with bad outcomes for all persons involved and linked intentional actions more strongly to positive outcomes, especially concerning the agent. People’s conceptions of intentional action seem to involve more aspects than commonly assumed in philosophical models of intentional action that solely stress the importance of intentions, desires, and beliefs. The additional aspects include decisions and thoughts about the action. In addition, we found that the criteria that participants generated for unintentional actions are not a mere inversion of those used in explanations for intentional actions. Associations between involuntariness and unintentional action seem to be stronger than associations between aspects of voluntariness and intentional action. PMID:26594182

  17. Action potential initiation and propagation in rat neocortical pyramidal neurons.

    PubMed

    Stuart, G; Schiller, J; Sakmann, B

    1997-12-15

    1. Initiation and propagation of action potentials evoked by extracellular synaptic stimulation was studied using simultaneous dual and triple patch pipette recordings from different locations on neocortical layer 5 pyramidal neurons in brain slices from 4-week-old rats (P26-30) at physiological temperatures. 2. Simultaneous cell-attached and whole-cell voltage recordings from the apical trunk (up to 700 microns distal to the soma) and the soma indicated that proximal synaptic stimulation (layer 4) initiated action potentials first at the soma, whereas distal stimulation (upper layer 2/3) could initiate dendritic regenerative potentials prior to somatic action potentials following stimulation at higher intensity. 3. Somatic action potentials, once initiated, propagated back into the apical dendrites in a decremented manner which was frequency dependent. The half-width of back propagating action potentials increased and their maximum rate of rise decreased with distance from the soma, with the peak of these action potentials propagating with a conduction velocity of approximately 0.5 m s-1. 4. Back-propagation of action potentials into the dendritic tree was associated with dendritic calcium electrogenesis, which was particularly prominent during bursts of somatic action potentials. 5. When dendritic regenerative potentials were evoked prior to somatic action potentials, the more distal the dendritic recording was made from the soma the longer the time between the onset of the dendritic regenerative potential relative to somatic action potential. This suggested that dendritic regenerative potentials were initiated in the distal apical dendrites, possibly in the apical tuft. 6. At any one stimulus intensity, the initiation of dendritic regenerative potentials prior to somatic action potentials could fluctuate, and was modulated by depolarizing somatic or hyperpolarizing dendritic current injection. 7. Dendritic regenerative potentials could be initiated prior to

  18. 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.

  19. Conduction velocity of antigravity muscle action potentials.

    PubMed

    Christova, L; Kosarov, D; Christova, P

    1992-01-01

    The conduction velocity of the impulses along the muscle fibers is one of the parameters of the extraterritorial potentials of the motor units allowing for the evaluation of the functional state of the muscles. There are no data about the conduction velocities of antigravity muscleaction potentials. In this paper we offer a method for measuring conduction velocity of potentials of single MUs and the averaged potentials of the interference electromiogram (IEMG) lead-off by surface electrodes from mm. sternocleidomastoideus, trapezius, deltoideus (caput laterale) and vastus medialis. The measured mean values of the conduction velocity of antigravity muscles potentials can be used for testing the functional state of the muscles.

  20. Atrial cell action potential parameter fitting using genetic algorithms.

    PubMed

    Syed, Z; Vigmond, E; Nattel, S; Leon, L J

    2005-09-01

    Understanding of the considerable variation in action potential (AP) shape throughout the heart is necessary to explain normal and pathological cardiac function. Existing mathematical models reproduce typical APs, but not all measured APs, as fitting the sets of non-linear equations is a tedious process. The study describes the integration of a pre-existing mathematical model of an atrial cell AP with a genetic algorithm to provide an automated tool to generate APs for arbitrary cells by fitting ionic channel conductances. Using the Nygren model as the base, the technique was first verified by starting with random values and fitting the Nygren model to itself with an error of only 0.03%. The Courtemanche model, which has a different morphology from that of the Nygren model, was successfully fitted. The AP duration restitution curve generated by the fit matched that of the target model very well. Finally, experimentally recorded APs were reproduced. To match AP duration restitution behaviour properly, it was necessary simultaneously to fit over several stimulation frequencies. Also, fitting of the upstroke was better if the stimulating current pulse replicated that found in situ as opposed to a rectangular pulse. In conclusion, the modelled parameters were successfully able to reproduce any given atrial AP. This tool can be useful for determining parameters in new AP models, reproducing specific APs, as well as determining the locus of drug action by examining changes in conductance values.

  1. Mathematical Distinction in Action Potential between Primo-Vessels and Smooth Muscle

    PubMed Central

    Cho, Seong-Jin; Lee, Sang-Hun; Zhang, Wenji; Lee, Sae-Bhom; Choi, Kwang-Ho; Choi, Sun-Mi; Ryu, Yeon-Hee

    2012-01-01

    We studied the action potential of Primo-vessels in rats to determine the electrophysiological characteristics of these structures. We introduced a mathematical analysis method, a normalized Fourier transform that displays the sine and cosine components separately, to compare the action potentials of Primo-vessels with those for the smooth muscle. We found that Primo-vessels generated two types of action potential pulses that differed from those of smooth muscle: (1) Type I pulse had rapid depolarizing and repolarizing phases, and (2) Type II pulse had a rapid depolarizing phase and a gradually slowing repolarizing phase. PMID:22319544

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

    PubMed Central

    Crago, Patrick E; Makowski, Nathan S

    2014-01-01

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

  3. 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

  4. Theophylline-induced potentiation of the antinociceptive action of baclofen.

    PubMed

    Sawynok, J

    1983-02-01

    1--Theophylline (35, 50 mg/kg) potentiated the antinociceptive action of intraperitoneally administered baclofen in the tail flick and hot plate tests. Potentiation was most marked when the pretreatment time was 1 h, but some potentiation was still apparent following a 2 h pretreatment. 2--Theophylline alone (50 mg/kg) produced only slight alterations in reaction latency in the two tests. 3--When baclofen was applied directly into the spinal subarachnoid space, a 1 h pretreatment with theophylline produced minimal effects, but a 2 h pretreatment produced an increase in the antinociceptive action of baclofen. 4--These results suggest that theophylline can potentiate the antinociceptive action of baclofen by actions at both supraspinal and spinal sites.

  5. Vector Potential Generation for Numerical Relativity Simulations

    NASA Astrophysics Data System (ADS)

    Silberman, Zachary; Faber, Joshua; Adams, Thomas; Etienne, Zachariah; Ruchlin, Ian

    2017-01-01

    Many different numerical codes are employed in studies of highly relativistic magnetized accretion flows around black holes. Based on the formalisms each uses, some codes evolve the magnetic field vector B, while others evolve the magnetic vector potential A, the two being related by the curl: B=curl(A). Here, we discuss how to generate vector potentials corresponding to specified magnetic fields on staggered grids, a surprisingly difficult task on finite cubic domains. The code we have developed solves this problem in two ways: a brute-force method, whose scaling is nearly linear in the number of grid cells, and a direct linear algebra approach. We discuss the success both algorithms have in generating smooth vector potential configurations and how both may be extended to more complicated cases involving multiple mesh-refinement levels. NSF ACI-1550436

  6. Hedonic value of intentional action provides reinforcement for voluntary generation but not voluntary inhibition of action.

    PubMed

    Parkinson, Jim; Haggard, Patrick

    2013-12-01

    Intentional inhibition refers to stopping oneself from performing an action at the last moment, a vital component of self-control. It has been suggested that intentional inhibition is associated with negative hedonic value, perhaps due to the frustration of cancelling an intended action. Here we investigate hedonic implications of the free choice to act or inhibit. Participants gave aesthetic ratings of arbitrary visual stimuli that immediately followed voluntary decisions to act or to inhibit action. We found that participants for whom decisions to act produced a strong positive hedonic value for the immediately following visual stimulus made more choices to act than those with weaker hedonic value for action. This finding is consistent with reinforcement learning of action decisions. However, participants who experienced inhibition as generating more positive hedonic value did not choose to inhibit more than other participants. Thus, voluntary inhibition of action did not act as reinforcement for future inhibitory behaviour. Our finding that inhibition of action lacks motivational capacity may explain why self-control is both difficult and limited.

  7. Dopamine gates action potential backpropagation in midbrain dopaminergic neurons.

    PubMed

    Gentet, Luc J; Williams, Stephen R

    2007-02-21

    Dopamine is released from both axonal and somatodendritic sites of midbrain dopaminergic neurons in an action potential-dependent manner. In contrast to the majority of central neurons, the axon of dopaminergic neurons typically originates from a dendritic site, suggesting a specialized computational function. Here, we examine the initiation and spread of action potentials in dopaminergic neurons of the substantia nigra pars reticulata and reveal that the displacement of the axon to a dendritic site allows highly compartmentalized electrical signaling. In response to a train of synaptic input, action potentials initiated at axon-bearing dendritic sites formed a variable trigger for invasion to the soma and contralateral dendritic tree, with action potentials often confined to the axon-bearing dendrite. The application of dopamine increased this form of electrical compartmentalization, an effect mediated by a tonic membrane potential hyperpolarization leading to an increased availability of a class of voltage-dependent potassium channel. These data suggest that the release of dopamine from axonal and somatodendritic sites are dissociable, and that dopamine levels within the midbrain are dynamically controlled by the somatodendritic spread of action potentials.

  8. Components of action potential repolarization in cerebellar parallel fibres

    PubMed Central

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

    2014-01-01

    Repolarization of the presynaptic action potential is essential for transmitter release, excitability and energy expenditure. Little is known about repolarization in thin, unmyelinated axons forming en passant synapses, which represent the most common type of axons in the mammalian brain's grey matter. We used rat cerebellar parallel fibres, an example of typical grey matter axons, to investigate the effects of K+ channel blockers on repolarization. We show that repolarization is composed of a fast tetraethylammonium (TEA)-sensitive component, determining the width and amplitude of the spike, and a slow margatoxin (MgTX)-sensitive depolarized after-potential (DAP). These two components could be recorded at the granule cell soma as antidromic action potentials and from the axons with a newly developed miniaturized grease-gap method. A considerable proportion of fast repolarization remained in the presence of TEA, MgTX, or both. This residual was abolished by the addition of quinine. The importance of proper control of fast repolarization was demonstrated by somatic recordings of antidromic action potentials. In these experiments, the relatively broad K+ channel blocker 4-aminopyridine reduced the fast repolarization, resulting in bursts of action potentials forming on top of the DAP. We conclude that repolarization of the action potential in parallel fibres is supported by at least three groups of K+ channels. Differences in their temporal profiles allow relatively independent control of the spike and the DAP, whereas overlap of their temporal profiles provides robust control of axonal bursting properties. PMID:25239461

  9. A fast algorithm for estimating actions in triaxial potentials

    NASA Astrophysics Data System (ADS)

    Sanders, Jason L.; Binney, James

    2015-03-01

    We present an approach to approximating rapidly the actions in a general triaxial potential. The method is an extension of the axisymmetric approach presented by Binney, and operates by assuming that the true potential is locally sufficiently close to some Stäckel potential. The choice of Stäckel potential and associated ellipsoidal coordinates is tailored to each individual input phase-space point. We investigate the accuracy of the method when computing actions in a triaxial Navarro-Frenk-White potential. The speed of the algorithm comes at the expense of large errors in the actions, particularly for the box orbits. However, we show that the method can be used to recover the observables of triaxial systems from given distribution functions to sufficient accuracy for the Jeans equations to be satisfied. Consequently, such models could be used to build models of external galaxies as well as triaxial components of our own Galaxy. When more accurate actions are required, this procedure can be combined with torus mapping to produce a fast convergent scheme for action estimation.

  10. 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.

  11. Video-Based Point Cloud Generation Using Multiple Action Cameras

    NASA Astrophysics Data System (ADS)

    Teo, T.

    2015-05-01

    Due to the development of action cameras, the use of video technology for collecting geo-spatial data becomes an important trend. The objective of this study is to compare the image-mode and video-mode of multiple action cameras for 3D point clouds generation. Frame images are acquired from discrete camera stations while videos are taken from continuous trajectories. The proposed method includes five major parts: (1) camera calibration, (2) video conversion and alignment, (3) orientation modelling, (4) dense matching, and (5) evaluation. As the action cameras usually have large FOV in wide viewing mode, camera calibration plays an important role to calibrate the effect of lens distortion before image matching. Once the camera has been calibrated, the author use these action cameras to take video in an indoor environment. The videos are further converted into multiple frame images based on the frame rates. In order to overcome the time synchronous issues in between videos from different viewpoints, an additional timer APP is used to determine the time shift factor between cameras in time alignment. A structure form motion (SfM) technique is utilized to obtain the image orientations. Then, semi-global matching (SGM) algorithm is adopted to obtain dense 3D point clouds. The preliminary results indicated that the 3D points from 4K video are similar to 12MP images, but the data acquisition performance of 4K video is more efficient than 12MP digital images.

  12. Drug-induced changes in action potential duration are proportional to action potential duration in rat ventricular myocardium.

    PubMed

    Bárándi, László; Harmati, Gábor; Horváth, Balázs; Szentandrássy, Norbert; Magyar, János; Varró, András; Nánási, Péter P; Bányász, Tamás

    2010-09-01

    Several cardioactive agents exhibit direct or reverse rate-dependent effects on action potential duration (APD) depending on the experimental conditions. Recently, a new theory has been proposed, suggesting that the reverse rate-dependent mode of drug-action may be a common property of canine, rabbit, guinea pig and human cardiac tissues, and this phenomenon is based on the dependence of drug-action on baseline APD. The aim of the present work was to examine the limitations of this hypothesis by studying the APD lengthening effect of K(+) channel blockers and the APD shortening effect of Ca(2+) channel blockers during the electrical restitution process of rat ventricular action potentials. Rat ventricular muscle was chosen because it has a set of ion currents markedly different from those of other species, its APD is shorter by one order of magnitude than that of the "plateau-forming" larger mammals, and most importantly, its APD increases at higher heart rates - opposite to many other species. The restitution of APD was studied as a function of the diastolic interval, a parameter indicating the proximity of action potentials. It was found that drug-induced APD changes in rat myocardium are proportional with the pre-drug value of APD but not with the diastolic interval, indicating that not the proximity of consecutive action potentials, but the baseline APD itself may determine the magnitude of drug-induced APD changes.

  13. Ultrafast action potentials mediate kilohertz signaling at a central synapse.

    PubMed

    Ritzau-Jost, Andreas; Delvendahl, Igor; Rings, Annika; Byczkowicz, Niklas; Harada, Harumi; Shigemoto, Ryuichi; Hirrlinger, Johannes; Eilers, Jens; Hallermann, Stefan

    2014-10-01

    Fast synaptic transmission is important for rapid information processing. To explore the maximal rate of neuronal signaling and to analyze the presynaptic mechanisms, we focused on the input layer of the cerebellar cortex, where exceptionally high action potential (AP) frequencies have been reported in vivo. With paired recordings between presynaptic cerebellar mossy fiber boutons and postsynaptic granule cells, we demonstrate reliable neurotransmission up to ∼1 kHz. Presynaptic APs are ultrafast, with ∼100 μs half-duration. Both Kv1 and Kv3 potassium channels mediate the fast repolarization, rapidly inactivating sodium channels ensure metabolic efficiency, and little AP broadening occurs during bursts of up to 1.5 kHz. Presynaptic Cav2.1 (P/Q-type) calcium channels open efficiently during ultrafast APs. Furthermore, a subset of synaptic vesicles is tightly coupled to Ca(2+) channels, and vesicles are rapidly recruited to the release site. These data reveal mechanisms of presynaptic AP generation and transmitter release underlying neuronal kHz signaling.

  14. Model-based source localization of extracellular action potentials.

    PubMed

    Somogyvári, Zoltán; Zalányi, László; Ulbert, István; Erdi, Péter

    2005-09-30

    A new model-based analysis method was set up for revealing information encrypted in extracellular spatial potential patterns of neocortical action potentials. Spikes were measured by extracellular linear multiple microelectrode in vivo cat's primary auditory cortex and were analyzed based on current source density (CSD) distribution models. Validity of the monopole and other point source approximations were tested on the measured potential patterns by numerical fitting. We have found, that point source models could not provide accurate description of the measured patterns. We introduced a new model of the CSD distribution on a spiking cell, called counter-current model (CCM). This new model was shown to provide better description of the spatial current distribution of the cell during the initial negative deflection of the extracellular action potential, from the onset of the spike to the negative peak. The new model was tested on simulated extracellular potentials. We proved numerically, that all the parameters of the model could be determined accurately based on measurements. Thus, fitting of the CCM allowed extraction of these parameters from the measurements. Due to model fitting, CSD could be calculated with much higher accuracy as done with the traditional method because distance dependence of the spatial potential patterns was explicitly taken into consideration in our method. Average CSD distribution of the neocortical action potentials was calculated and spatial decay constant of the dendritic trees was determined by applying our new method.

  15. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2016-03-01

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

  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. Action potential and contraction of Dionaea muscipula (Venus flytrap).

    PubMed

    DI PALMA, J R; MOHL, R; BEST, W

    1961-03-24

    Observation of the action potential and contraction of the leaf of Dionaea muscipula Ellis revealed several interesting phenomena. Two successive stimuli are generally necessary to cause contraction. The first and ineffective stimulus is associated with slow depolarization. The second stimulus has much more rapid depolarization and initiates contraction.

  20. 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…

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

    PubMed Central

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

    1970-01-01

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

  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.

  3. Generativity Does Not Necessarily Satisfy All Your Needs: Associations among Cultural Demand for Generativity, Generative Concern, Generative Action, and Need Satisfaction in the Elderly in Four Cultures

    ERIC Educational Resources Information Center

    Hofer, Jan; Busch, Holger; Au, Alma; Polácková Šolcová, Iva; Tavel, Peter; Tsien Wong, Teresa

    2016-01-01

    The present study examines the association between various facets of generativity, that is, cultural demand for generativity, generative concern, and generative action, with the satisfaction of the needs for relatedness, competence, and autonomy in samples of elderly from Cameroon, China (Hong Kong), the Czech Republic, and Germany. Participants…

  4. Ionic currents underlying the action potential of Rana pipiens oocytes.

    PubMed

    Schlichter, L C

    1989-07-01

    Ionic currents in immature, ovulated Rana pipiens oocytes (metaphase I) were studied using the voltage-clamp technique. At this stage of maturity the oocyte can produce action potentials in response to depolarizing current or as an "off response" to hyperpolarizing current. Reducing external Na+ to 1/10 normal (choline substituted) eliminated the action potentials and both the negative-slope region and zero-crossing of the I-V relation. Reducing external Cl- to 1/10 or 1/100 normal (methanesulfonate substituted) lengthened the action potential. The outward current was reduced and a net inward current was revealed. By changing external Na+, Cl-, and K+ concentrations and using blocking agents (SITS, TEA), three voltage- and time-dependent currents were identified, INa, IK and ICl. The Na+ current activated at about 0 mV and reversed at very positive values which decreased during maturation. Inward Na+ current produced the upstroke of the action potential. During each voltage-clamp step the Na+ current activated slowly (seconds) and did not inactivate within many minutes. The Na+ current was not blocked by TTX at micromolar concentrations. The K+ current was present only in the youngest oocytes. Because IK was superimposed on a large leakage current, it appeared to reverse at the resting potential. When leakage currents were subtracted, the reversal potential for IK was more negative than -110 mV in Ringer's solution. IK was outwardly rectifying and strongly activated above -50 mV. The outward K+ current produced an after hyperpolarization at the end of each action potential. IK was blocked completely and reversibly by 20 mM external TEA. The Cl- current activated at about +10 mV and was outwardly rectifying. ICl was blocked completely and reversibly by 400 microM SITS added to the bathing medium. This current helped repolarize the membrane following an action potential in the youngest oocytes and was the only repolarizing current in more mature oocytes that had lost

  5. K+-induced twitch potentiation is not due to longer action potential.

    PubMed

    Yensen, Craig; Matar, Wadih; Renaud, Jean-Marc

    2002-07-01

    The objective of this study was to determine whether an increased duration of the action potential contributes to the K+-induced twitch potentiation at 37 degrees C. Twitch contractions were elicited by field stimulation, and action potentials were measured with conventional microelectrodes. For mouse extensor digitorum longus (EDL) muscle, twitch force was greater at 7-13 mM K+ than at 4.7 mM (control). For soleus muscle, twitch force potentiation was observed between 7 and 11 mM K+. Time to peak and half-relaxation time were not affected by the increase in extracellular K+ concentration in EDL muscle, whereas both parameters became significantly longer in soleus muscle. Decrease in overshoot and prolongation of the action potential duration observed at 9 and 11 mM K+ were mimicked when muscles were respectively exposed to 25 and 50 nM tetrodotoxin (TTX; used to partially block Na+ channels). Despite similar action potentials, twitch force was not potentiated by TTX. It is therefore suggested that the K+-induced potentiation of the twitch in EDL muscle is not due to a prolongation of the action potential and contraction time, whereas a longer contraction, especially the relaxation phase, may contribute to the potentiation in soleus muscle.

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

    PubMed

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

    2015-07-01

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

  7. Exploring potential Pluto-generated neutral tori

    NASA Astrophysics Data System (ADS)

    Smith, Howard T.; Hill, Matthew; KollMann, Peter; McHutt, Ralph

    2015-11-01

    The NASA New Horizons mission to Pluto is providing unprecedented insight into this mysterious outer solar system body. Escaping molecular nitrogen is of particular interest and possibly analogous to similar features observed at moons of Saturn and Jupiter. Such escaping N2 has the potential of creating molecular nitrogen and N (as a result of molecular dissociation) tori or partial toroidal extended particle distributions. The presence of these features would present the first confirmation of an extended toroidal neutral feature on a planetary scale in our solar system. While escape velocities are anticipated to be lower than those at Enceladus, Io or even Europa, particle lifetimes are much longer in Pluto’s orbit because as a result of much weaker solar interaction processes along Pluto’s orbit (on the order of tens of years). Thus, with a ~248 year orbit, Pluto may in fact be generating an extended toroidal feature along it orbit.For this work, we modify and apply our 3-D Monte Carlo neutral torus model (previously used at Saturn, Jupiter and Mercury) to study/analyze the theoretical possibility and scope of potential Pluto-generated neutral tori. Our model injects weighted particles and tracks their trajectories under the influence of all gravitational fields with interactions with other particles, solar photons and Pluto collisions. We present anticipated N2 and N tori based on current estimates of source characterization and environmental conditions. We also present an analysis of sensitivity to assumed initial conditions. Such results can provide insight into the Pluto system as well as valuable interpretation of New Horizon’s observational data.

  8. Focused ultrasound effects on nerve action potential in vitro

    PubMed Central

    Colucci, Vincent; Strichartz, Gary; Jolesz, Ferenc; Vykhodtseva, Natalia; Hynynen, Kullervo

    2009-01-01

    Minimally invasive applications of thermal and mechanical energy to selective areas of the human anatomy have led to significant advances in treatment of and recovery from typical surgical interventions. Image-guided focused ultrasound allows energy to be deposited deep into the tissue, completely noninvasively. There has long been interest in using this focal energy delivery to block nerve conduction for pain control and local anesthesia. In this study, we have performed an in vitro study to further extend our knowledge of this potential clinical application. The sciatic nerves from the bullfrog (Rana catesbeiana) were subjected to focused ultrasound (at frequencies of 0.661MHz and 1.986MHz) and to heated Ringer’s solution. The nerve action potential was shown to decrease in the experiments and correlated with temperature elevation measured in the nerve. The action potential recovered either completely, partially, or not at all, depending on the parameters of the ultrasound exposure. The reduction of the baseline nerve temperature by circulating cooling fluid through the sonication chamber did not prevent the collapse of the nerve action potential; but higher power was required to induce the same endpoint as without cooling. These results indicate that a thermal mechanism of focused ultrasound can be used to block nerve conduction, either temporarily or permanently. PMID:19647923

  9. Using extracellular action potential recordings to constrain compartmental models.

    PubMed

    Gold, Carl; Henze, Darrell A; Koch, Christof

    2007-08-01

    We investigate the use of extracellular action potential (EAP) recordings for biophysically faithful compartmental models. We ask whether constraining a model to fit the EAP is superior to matching the intracellular action potential (IAP). In agreement with previous studies, we find that the IAP method under-constrains the parameters. As a result, significantly different sets of parameters can have virtually identical IAP's. In contrast, the EAP method results in a much tighter constraint. We find that the distinguishing characteristics of the waveform--but not its amplitude-resulting from the distribution of active conductances are fairly invariant to changes of electrode position and detailed cellular morphology. Based on these results, we conclude that EAP recordings are an excellent source of data for the purpose of constraining compartmental models.

  10. Stability of Cardiac Action Potential Duration under Periodic Pacing.

    PubMed

    Xiaodong, Han; Hailang, Song; Xiaomei, Wu; Cuiwei, Yang; Zuxiang, Fang

    2005-01-01

    Action potential duration (APD) alternans is believed to be a loss of stability and contributes much to the reentry arrhythmias. The purpose of this study is to analyze the stability conditions for one-dimension model and higher dimension model. These criterions are concluded by linear stability analysis in nonlinear dynamics. They should be useful for finding of cardiac control algorithms in low energy defibrillation and the designing of antiarrhythmic drug.

  11. Evidence for the Automatic Evaluation of Self-Generated Actions

    ERIC Educational Resources Information Center

    Aarts, Kristien; De Houwer, Jan; Pourtois, Gilles

    2012-01-01

    The accuracy of simple actions is swiftly determined through specific monitoring brain systems. However, it remains unclear whether this evaluation is accompanied by a rapid and compatible emotional appraisal of the action that allows to mark incorrect actions as negative/bad and conversely correct actions as positive/good. In this study, we used…

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

    PubMed

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

    2012-10-25

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

  13. Variations in onset of action potential broadening: effects on calcium current studied in chick ciliary ganglion neurones.

    PubMed

    Pattillo, J M; Artim, D E; Simples, J E; Meriney, S D

    1999-02-01

    1. The voltage dependence and kinetic properties of stage 40 ciliary ganglion calcium currents were determined using short (10 ms) voltage steps. These properties aided the interpretation of the action potential-evoked calcium current described below, and the comparison of our data with those observed in other preparations. 2. Three different natural action potential waveforms were modelled by a series of ramps to generate voltage clamp commands. Calcium currents evoked by these model action potentials were compared before and after alterations in the repolarization phase of each action potential. 3. Abrupt step repolarizations from various time points were used to estimate the time course of calcium current activation during each action potential. Calcium current evoked by fast action potentials (duration at half-amplitude, 0.5 or 1.0 ms) did not reach maximal activation until the action potential had repolarized by 40-50 %. In contrast, calcium current evoked by a slow action potential (duration at half-amplitude, 2.2 ms) was maximally activated near the peak of the action potential. 4. Slowing the rate of repolarization of the action potential (broadening) from different times was used to examine effects on peak and total calcium influx. With all three waveforms tested, broadening consistently increased total calcium influx (integral). However, peak calcium current was either increased or decreased depending on the duration of the control action potential tested and the specific timing of the initiation of broadening the repolarization phase. 5. The opposite effects on peak calcium current observed with action potential broadening beginning at different time points in repolarization may provide a mechanism for the variable effects of potassium channel blockers on transmitter release magnitude.

  14. 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.

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

    PubMed

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

    2013-07-01

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

  16. Variation potential in higher plants: Mechanisms of generation and propagation

    PubMed Central

    Vodeneev, Vladimir; Akinchits, Elena; Sukhov, Vladimir

    2015-01-01

    Long-distance intercellular electrical signals, including variation potential (VP) in higher plants, are a potential mechanism of coordinate functional responses in different plant cells under action of stressors. VP, which is caused by damaging factors (e.g., heating, crushing), is transient depolarization with an irregular shape. It can include a long-term depolarization and fast impulse depolarization (‘AP-like’ spikes). Mechanisms of VP generation and propagation are still under investigation. It is probable that VP is a local electrical response induced by propagation of hydraulic wave and (or) chemical agent. Both hypotheses are based on numerous experimental results but they predict VP velocities which are not in a good accordance with speed of variation potential propagation. Thus combination of hydraulic and chemical signals is the probable mechanism of VP propagation. VP generation is traditionally connected with transient H+-ATPase inactivation, but AP-like spikes are also connected with passive ions fluxes. Ca2+ influx is a probable mechanism which triggers H+-ATPase inactivation and ions channels activation at VP. PMID:26313506

  17. Information Encoding and Reconstruction from the Phase of Action Potentials

    PubMed Central

    Nadasdy, Zoltan

    2009-01-01

    Fundamental questions in neural coding are how neurons encode, transfer, and reconstruct information from the pattern of action potentials (APs) exchanged between different brain structures. We propose a general model of neural coding where neurons encode information by the phase of their APs relative to their subthreshold membrane oscillations. We demonstrate by means of simulations that AP phase retains the spatial and temporal content of the input under the assumption that the membrane potential oscillations are coherent across neurons and between structures and have a constant spatial phase gradient. The model explains many unresolved physiological observations and makes a number of concrete, testable predictions about the relationship between APs, local field potentials, and subthreshold membrane oscillations, and provides an estimate of the spatio-temporal precision of neuronal information processing. PMID:19668700

  18. Intracochlear and extracochlear ECAPs suggest antidromic action potentials.

    PubMed

    Miller, Charles A; Abbas, Paul J; Hay-McCutcheon, Marcia J; Robinson, Barbara K; Nourski, Kirill V; Jeng, Fuh-Cherng

    2004-12-01

    With experimental animals, the electrically evoked compound action potential (ECAP) can be recorded from multiple sites (e.g., round window, intracranial and intracochlear sites). However, human ECAPs are typically recorded from intracochlear electrodes of the implanted array. To bridge this difference, we obtained ECAPs from cats using both intracochlear and nerve-trunk recording sites. We also sought to determine how recording the site influences the acquired evoked potential and how those differences may provide insight into basic excitation properties. In the main experiment, ECAPs were recorded from four acutely deafened cats after implanting a Nucleus-style banded electrode array. Potentials were recorded from an electrode positioned on the nerve trunk and an intracochlear electrode. We manipulated stimulus level, electrode configuration (monopolar vs bipolar) and stimulus polarity, variables that influence the site of excitation. Intracochlear ECAPs were found to be an order of magnitude greater than those obtained with the nerve-trunk electrode. Also, compared with the nerve-trunk potentials, the intracochlear ECAPs more closely resembled those obtained from humans in that latencies were shorter and the waveform morphology was typically biphasic (a negative peak followed by a positive peak). With anodic monophasic stimuli, the ECAP had a unique positive-to-negative morphology which we attributed to antidromic action potentials resulting from a relatively central site of excitation. We also collected intracochlear ECAPs from twenty Nucleus 24 implant users. Compared with the feline ECAPs, the human potentials had smaller amplitudes and longer latencies. It is not clear what underlies these differences, although several factors are considered.

  19. Action currents, internodal potentials, and extracellular records of myelinated mammalian nerve fibers derived from node potentials.

    PubMed Central

    Marks, W B; Loeb, G E

    1976-01-01

    The potential distribution within the internodal axon of mammalian nerve fibers is derived by applying known node potential waveforms to the ends of an equivalent circuit model of the internode. The complete spatial/temporal profile of action potentials synthesized from the internodal profiles is used to compute the node current waveforn, and the extracellular action potential around fibers captured within a tubular electrode. For amphibia, the results agreed with empirical values. For mammals, the amplitude of the node currents plotted against conduction velocity was fitted by a straight line. The extracellular potential waveform depended on the location of the nodes within the tube. For tubes of length from 2 to 8 internodes, extracellular wave amplitude (mammals) was about one-third of the product of peak node current and tube resistance (center to ends). The extracellular potentials developed by longitudinal and radial currents in an anisotropic medium (fiber bundle) are compared. PMID:1276389

  20. A mathematical model of action potential in cells of vascular plants.

    PubMed

    Sukhov, Vladimir; Vodeneev, Vladimir

    2009-12-01

    A mathematical model of action potential (AP) in vascular plants cells has been worked out. The model takes into account actions of plasmalemma ion transport systems (K(+), Cl(-) and Ca(2+) channels; H(+)- and Ca(2+)-ATPases; 2H(+)/Cl(-) symporter; and H(+)/K(+) antiporter), changes of ion concentrations in the cell and in the extracellular space, cytoplasmic and apoplastic buffer capacities and the temperature dependence of active transport systems. The model of AP simulates a stationary level of the membrane potential and ion concentrations, generation of AP induced by electrical stimulation and gradual cooling and the impact of external Ca(2+) for AP development. The model supports a hypothesis about participation of H(+)-ATPase in AP generation.

  1. 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.

  2. 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

  3. 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.

  4. 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.

  5. Using affective knowledge to generate and validate a set of emotion-related, action words

    PubMed Central

    Havelka, Jelena; Brown, Charity; Giner-Sorolla, Roger

    2015-01-01

    Emotion concepts are built through situated experience. Abstract word meaning is grounded in this affective knowledge, giving words the potential to evoke emotional feelings and reactions (e.g., Vigliocco et al., 2009). In the present work we explore whether words differ in the extent to which they evoke ‘specific’ emotional knowledge. Using a categorical approach, in which an affective ‘context’ is created, it is possible to assess whether words proportionally activate knowledge relevant to different emotional states (e.g., ‘sadness’, ‘anger’, Stevenson, Mikels & James, 2007a). We argue that this method may be particularly effective when assessing the emotional meaning of action words (e.g., Schacht & Sommer, 2009). In study 1 we use a constrained feature generation task to derive a set of action words that participants associated with six, basic emotional states (see full list in Appendix S1). Generation frequencies were taken to indicate the likelihood that the word would evoke emotional knowledge relevant to the state to which it had been paired. In study 2 a rating task was used to assess the strength of association between the six most frequently generated, or ‘typical’, action words and corresponding emotion labels. Participants were presented with a series of sentences, in which action words (typical and atypical) and labels were paired e.g., “If you are feeling ‘sad’ how likely would you be to act in the following way?” … ‘cry.’ Findings suggest that typical associations were robust. Participants always gave higher ratings to typical vs. atypical action word and label pairings, even when (a) rating direction was manipulated (the label or verb appeared first in the sentence), and (b) the typical behaviours were to be performed by the rater themselves, or others. Our findings suggest that emotion-related action words vary in the extent to which they evoke knowledge relevant for different emotional states. When measuring

  6. Zinc-dependent action potentials in giant neurons of the snail, Euhadra quaestia.

    PubMed

    Kawa, K

    1979-09-14

    In giant neurons of subesophageal ganglion of the Japanese land snail, Euhadra quaestia Deshayes, permeation of Zn ions through Ca channels were investigated with a conventional current clamp method. All-or-none action potentials of long duration (90 to 120 sec) were evoked in 24 mM Zn containing salines. The overshoots were about +10 mV and the maximum rate of rises (MRRs) was about 2.9 V/sec. The amplitudes and the MRRs of the action potentials depended on external Zn ion concentrations. The action potentials were suppressed by specific Ca-channel inhibitors such as Co2+, La3+ and Verapamil, but they were resistant to Na-channel inhibitor, tetrodotoxin, even at 30 microM. It is concluded that these action potentials are generated by Zn ions permeating Ca channels in snail neuronal membrane. On the basis of Hagiwara and Takahashi's (S. Hagiwara & K. Takahashi, 1967, J. Gen. Physiol. 50:583) model of Ca channels, it is inferred that Zn ions are 5 to 10 times stronger in affinity to Ca channels than Ca ions, but 10 to 20 times less permeable.

  7. 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…

  8. Narrow and wide field amacrine cells fire action potentials in response to depolarization and light stimulation.

    PubMed

    Heflin, Stephanie J; Cook, Paul B

    2007-01-01

    Action potentials in amacrine cells are important for lateral propagation of signals across the inner retina, but it is unclear how many subclasses of amacrine cells contain voltage-gated sodium channels or can fire action potentials. This study investigated the ability of amacrine cells with narrow ( <200 microm) and wide (>200 microm) dendritic fields to fire action potentials in response to depolarizing current injections and light stimulation. The pattern of action potentials evoked by current injections revealed two distinct classes of amacrine cells; those that responded with a single action potential (single-spiking cells) and those that responded with repetitive action potentials (repetitive-spiking cells). Repetitive-spiking cells differed from single-spiking cells in several regards: Repetitive-spiking cells were more often wide field cells, while single-spiking cells were more often narrow field cells. Repetitive-spiking cells had larger action potential amplitudes, larger peak voltage-gated NaV currents lower action potential thresholds, and needed less current to induce action potentials. However, there was no difference in the input resistance, holding current or time constant of these two classes of cells. The intrinsic capacity to fire action potentials was mirrored in responses to light stimulation; single-spiking amacrine cells infrequently fired action potentials to light steps, while repetitive-spiking amacrine cells frequently fired numerous action potentials. These results indicate that there are two physiologically distinct classes of amacrine cells based on the intrinsic capacity to fire action potentials.

  9. Temperature dependence of action potential parameters in Aplysia neurons.

    PubMed

    Hyun, Nam Gyu; Hyun, Kwang-Ho; Lee, Kyungmin; Kaang, Bong-Kiun

    2012-01-01

    Although the effects of temperature changes on the activity of neurons have been studied in Aplysia, the reproducibility of the temperature dependence of the action potential (AP) parameters has not been verified. To this end, we performed experiments using Aplysia neurons. Fourteen AP parameters were analyzed using the long-term data series recorded during the experiments. Our analysis showed that nine of the AP parameters decreased as the temperature increased: the AP amplitude (A(AP)), membrane potential at the positive peak (V(pp)), interspike interval, first half (Δt(r1)) and last half (Δt(r2)) of the temperature rising phase, first half (Δt(f1)) and last half (Δt(f2)) of the temperature falling phase, AP (Δt(AP, 1/2)), and differentiated signal (Δt(DS, 1/2)) half-width durations. Five of the AP parameters increased with temperature: the differentiated signal amplitude (A(DS)), absolute value of the membrane potential at negative peak (|V(np)|), absolute value of the maximum slope of the AP during the temperature rising (|-MSR|) and falling (|MSF|) phases, and spiking frequency (Frequency). This work could provide the basis for a better understanding of the elementary processes underlying the temperature-dependent neuronal activity in Aplysia.

  10. Next generation interatomic potentials for condensed systems

    NASA Astrophysics Data System (ADS)

    Handley, Christopher Michael; Behler, Jörg

    2014-07-01

    The computer simulation of condensed systems is a challenging task. While electronic structure methods like density-functional theory (DFT) usually provide a good compromise between accuracy and efficiency, they are computationally very demanding and thus applicable only to systems containing up to a few hundred atoms. Unfortunately, many interesting problems require simulations to be performed on much larger systems involving thousands of atoms or more. Consequently, more efficient methods are urgently needed, and a lot of effort has been spent on the development of a large variety of potentials enabling simulations with significantly extended time and length scales. Most commonly, these potentials are based on physically motivated functional forms and thus perform very well for the applications they have been designed for. On the other hand, they are often highly system-specific and thus cannot easily be transferred from one system to another. Moreover, their numerical accuracy is restricted by the intrinsic limitations of the imposed functional forms. In recent years, several novel types of potentials have emerged, which are not based on physical considerations. Instead, they aim to reproduce a set of reference electronic structure data as accurately as possible by using very general and flexible functional forms. In this review we will survey a number of these methods. While they differ in the choice of the employed mathematical functions, they all have in common that they provide high-quality potential-energy surfaces, while the efficiency is comparable to conventional empirical potentials. It has been demonstrated that in many cases these potentials now offer a very interesting new approach to study complex systems with hitherto unreached accuracy.

  11. Toxin detection based on action potential shape analysis using a realistic mathematical model of differentiated NG108-15 cells

    PubMed Central

    Mohan, Dinesh K; Molnar, Peter; Hickman, James J.

    2010-01-01

    The NG108-15 neuroblastoma / glioma hybrid cell line has been frequently used for toxin detection, pharmaceutical screening and as a whole-cell biosensor. However, detailed analysis of its action potentials during toxin or drug administration has not been accomplished previously using patch clamp electrophysiology. In order to explore the possibility of identifying toxins based on their effect on the shape of intracellularly or extracellularly detected action potentials, we created a computer model of the action potential generation of this cell type. To generate the experimental data to validate the model, voltage dependent sodium, potassium and high-threshold calcium currents, as well as action potentials, were recorded from NG108-15 cells with conventional whole-cell patch-clamp methods. Based on the classic Hodgkin-Huxley formalism and the linear thermodynamic description of the rate constants, ion-channel parameters were estimated using an automatic fitting method. Utilizing the established parameters, action potentials were generated in the model and were optimized to represent the actual recorded action potentials to establish baseline conditions. To demonstrate the applicability of the method for toxin detection and discrimination, the effect of tetrodotoxin (a sodium channel blocker) and tefluthrin (a pyrethroid that is a sodium channel opener) were studied. The two toxins affected the shape of the action potentials differently and their respective effects were identified based on the changes in the fitted parameters. Our results represent one of the first steps to establish a complex model of NG108-15 cells for quantitative toxin detection based on action potential shape analysis of the experimental results. PMID:16460924

  12. Visual Cues Generated during Action Facilitate 14-Month-Old Infants' Mental Rotation

    ERIC Educational Resources Information Center

    Antrilli, Nick K.; Wang, Su-hua

    2016-01-01

    Although action experience has been shown to enhance the development of spatial cognition, the mechanism underlying the effects of action is still unclear. The present research examined the role of visual cues generated during action in promoting infants' mental rotation. We sought to clarify the underlying mechanism by decoupling different…

  13. Ionic channel function in action potential generation: current perspective.

    PubMed

    Baranauskas, Gytis

    2007-04-01

    Over 50 years ago, Hodgkin and Huxley laid down the foundations of our current understanding of ionic channels. An impressive progress has been made during the following years that culminated in the revelation of the details of potassium channel structure. Nevertheless, even today, we cannot separate well currents recorded in central mammalian neurons. Many modern concepts about the function of sodium and potassium currents are based on experiments performed in nonmammalian cells. The recent recognition of the fast delayed rectifier current indicates that we need to reevaluate the biophysical role of sodium and potassium currents. This review will consider high quality voltage clamp data obtained from the soma of central mammalian neurons in the view of our current knowledge about proteins forming ionic channels. Fast sodium currents and three types of outward potassium currents, the delayed rectifier, the subthreshold A-type, and the D-type potassium currents, are discussed here. An updated current classification with biophysical role of each current subtype is provided. This review shows that details of kinetics of both sodium and outward potassium currents differ significantly from the classical descriptions and these differences may be of functional significance.

  14. Apathy in schizophrenia as a deficit in the generation of options for action.

    PubMed

    Hartmann, Matthias N; Kluge, Agne; Kalis, Annemarie; Mojzisch, Andreas; Tobler, Philippe N; Kaiser, Stefan

    2015-05-01

    Negative symptoms are a core feature of schizophrenia and have been grouped into 2 factors: a motivational factor, which we refer to as apathy, and a diminished expression factor. Recent studies have shown that apathy is closely linked to functional outcome. However, knowledge about its mechanisms and its relation to decision-making is limited. In the current study, we examined whether apathy in schizophrenia is associated with predecisional deficits, that is, deficits in the generation of options for action. We applied verbal protocol analysis to investigate the quantity of options generated in ill-structured real world scenarios in 30 patients with schizophrenia or schizoaffective disorder and 21 healthy control participants. Patients generated significantly fewer options than control participants and clinical apathy ratings correlated negatively with the quantity of generated options. We show that the association between measures of psychopathology and option generation is most pronounced in regard to apathy symptoms and that it is only partially mediated by deficits in verbal fluency. This study provides empirical support for dysfunctional option generation as a possible mechanism for apathy in schizophrenia. Our data emphasize the potential importance of predecisional stages in the development and persistence of apathy symptoms in neuropsychiatric disorders and might also inform the development of novel treatment options in the realm of cognitive remediation.

  15. Potential anti-inflammatory actions of the elmiric (lipoamino) acids

    PubMed Central

    Burstein, Sumner H.; Adams, Jeffrey K.; Bradshaw, Heather B.; Fraioli, Cristian; Rossetti, Ronald G.; Salmonsen, Rebecca A.; Shaw, John W.; Walker, J. Michael; Zipkin, Robert E.; Zurier, Robert B.

    2007-01-01

    A library of amino acid-fatty acid conjugates (elmiric acids) was synthesized and evaluated for activity as potential anti-inflammatory agents. The compounds were tested in vitro for their effects on cell proliferation and prostaglandin production and compared with their effects on in vivo models of inflammation. LPS stimulated RAW 267.4 mouse macrophage cells was the in vitro model and phorbol ester-induced mouse ear edema served as the principal in vivo model. The prostaglandin responses were found to be strongly dependent on the nature of the fatty acid part of the molecule. Polyunsaturated acid conjugates produced a marked increase in media levels of i15-deoxy-PGJ2 with minimal effects on PGE production. It is reported in the literature that prostaglandin ratios in which the J series predominates over the E series promote the resolution of inflammatory conditions. Several of the elmiric acids tested here produced such favorable ratios suggesting that their potential anti-inflammatory activity occurs via a novel mechanism of action. The ear edema assay results were generally in agreement with the prostaglandin assay findings indicating a connection between them. PMID:17383881

  16. Global potential for wind-generated electricity.

    PubMed

    Lu, Xi; McElroy, Michael B; Kiviluoma, Juha

    2009-07-07

    The potential of wind power as a global source of electricity is assessed by using winds derived through assimilation of data from a variety of meteorological sources. The analysis indicates that a network of land-based 2.5-megawatt (MW) turbines restricted to nonforested, ice-free, nonurban areas operating at as little as 20% of their rated capacity could supply >40 times current worldwide consumption of electricity, >5 times total global use of energy in all forms. Resources in the contiguous United States, specifically in the central plain states, could accommodate as much as 16 times total current demand for electricity in the United States. Estimates are given also for quantities of electricity that could be obtained by using a network of 3.6-MW turbines deployed in ocean waters with depths <200 m within 50 nautical miles (92.6 km) of closest coastlines.

  17. Global potential for wind-generated electricity

    PubMed Central

    Lu, Xi; McElroy, Michael B.; Kiviluoma, Juha

    2009-01-01

    The potential of wind power as a global source of electricity is assessed by using winds derived through assimilation of data from a variety of meteorological sources. The analysis indicates that a network of land-based 2.5-megawatt (MW) turbines restricted to nonforested, ice-free, nonurban areas operating at as little as 20% of their rated capacity could supply >40 times current worldwide consumption of electricity, >5 times total global use of energy in all forms. Resources in the contiguous United States, specifically in the central plain states, could accommodate as much as 16 times total current demand for electricity in the United States. Estimates are given also for quantities of electricity that could be obtained by using a network of 3.6-MW turbines deployed in ocean waters with depths <200 m within 50 nautical miles (92.6 km) of closest coastlines. PMID:19549865

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

    PubMed

    Takagi, Hiroaki; Hashitani, Hikaru

    2016-10-15

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

  19. Action Generation Model Based on Changes in State Patterns

    NASA Astrophysics Data System (ADS)

    Gouko, Manabu; Tomi, Naoki; Nagano, Tomoaki; Ito, Koji

    In this paper, we propose a self-organized learning model that can generate behaviors for successfully performing various tasks. The model memorizes various relationships between changes in a state pattern and a motor command through learning. After the learning, the model can perform various tasks by generating the various behaviors automatically. We confirmed the performance of the model by applying it to a mobile robot simulation. The results indicate that suitable behaviors for all the tasks generated spontaneously. Additionally, we propose a sequential learning method which modifies the memorized various relationships while the model executes the task. And we confirmed the effectiveness of the sequential learning by the simulation.

  20. Metabolic Energy of Action Potentials Modulated by Spike Frequency Adaptation

    PubMed Central

    Yi, Guo-Sheng; Wang, Jiang; Li, Hui-Yan; Wei, Xi-Le; Deng, Bin

    2016-01-01

    Spike frequency adaptation (SFA) exists in many types of neurons, which has been demonstrated to improve their abilities to process incoming information by synapses. The major carrier used by a neuron to convey synaptic signals is the sequences of action potentials (APs), which have to consume substantial metabolic energies to initiate and propagate. Here we use conductance-based models to investigate how SFA modulates the AP-related energy of neurons. The SFA is attributed to either calcium-activated K+ (IAHP) or voltage-activated K+ (IM) current. We observe that the activation of IAHP or IM increases the Na+ load used for depolarizing membrane, while produces few effects on the falling phase of AP. Then, the metabolic energy involved in Na+ current significantly increases from one AP to the next, while for K+ current it is less affected. As a consequence, the total energy cost by each AP gets larger as firing rate decays down. It is also shown that the minimum Na+ charge needed for the depolarization of each AP is unaffected during the course of SFA. This indicates that the activation of either adaptation current makes APs become less efficient to use Na+ influx for their depolarization. Further, our simulations demonstrate that the different biophysical properties of IM and IAHP result in distinct modulations of metabolic energy usage for APs. These investigations provide a fundamental link between adaptation currents and neuronal energetics, which could facilitate to interpret how SFA participates in neuronal information processing. PMID:27909394

  1. Steroid inhibitors of androgen-potentiated actions on skin.

    PubMed

    Ebling, F J; Randall, V A

    1983-07-01

    Antiandrogens, such as cyproterone acetate, and oestrogens both inhibit sebaceous secretion in rats and have a potentiality for the treatment of hirsutism and acne in the human female. However, they act at different points. In castrated rats treated with testosterone, 3 micrograms/day oestradiol produced a greater decrease in sebum secretion than a dose of cyproterone acetate over 1000 times larger; moreover the antiandrogen reduced the incidence of sebaceous mitoses whereas the oestradiol did not. In hirsute women, oral administration of 100 mg of cyproterone acetate daily caused a 40% reduction in sebum secretion within 10 days; a further 20% was subsequently produced by combined therapy with cyproterone acetate and ethinyloestradiol. Significant decreases in the diameter and rate of growth of thigh hairs were not established until around the fourth monthly cycle of treatment. The actions were believed to be mainly peripheral, though contributory factors could also have been the small but significant reductions in plasma androgens produced by the antiandrogen, and the marked rise in sex hormone binding globulin produced by the oestrogen. That it is theoretically possible for cyproterone acetate or oestradiol to act locally follows from an unequivocal demonstration that either compound produced a local depression of sebum secretion when applied topically to rats.

  2. 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.

  3. Effects of troglitazone and pioglitazone on the action potentials and membrane currents of rabbit ventricular myocytes.

    PubMed

    Ikeda, S; Watanabe, T

    1998-09-18

    The effects of the antidiabetic thiazolidinediones troglitazone and pioglitazone on action potentials and membrane currents were studied in rabbit ventricular myocytes. Troglitazone (10 microM) reversibly reduced excitability of the myocytes and modified their action potential configuration. It significantly increased the stimulation threshold required to elicit action potentials and decreased action potential amplitude and the maximum upstroke velocity of the action potentials. The Inhibition of the maximum upstroke velocity by troglitazone was also significant at 1 microM. Voltage-clamp experiments revealed that troglitazone (10 microM) reversibly inhibited both the slow inward Ca2+ current and the steady-state K+ current. In contrast to troglitazone, pioglitazone (1-10 microM) had no significant effect on the excitability, action potential configuration, or membrane currents of myocytes. These results suggest that troglitazone, but not pioglitazone, modulates Na+, Ca2+ and K+ currents, leading to the changes in excitability and action potential configuration of ventricular myocytes.

  4. Development of action potentials and apamin-sensitive after-potentials in mouse vestibular nucleus neurones.

    PubMed

    Dutia, M B; Johnston, A R

    1998-01-01

    The postnatal maturation of medial vestibular nucleus (MVN) neurones was examined in slices of the dorsal brainstem prepared from balb/c mice at specific stages during the first postnatal month. Using spike-shape averaging to analyse the intracellularly recorded action potentials and after-hyperpolarizations (AHPs) in each cell, all the MVN neurones recorded in the young adult (postnatal day 30; P30) mouse were shown to have either a single deep AHP (type A cells), or an early fast and a delayed slow AHP (type B cells). The relative proportions of the two subtypes were similar to those in the young adult rat. At P5, all the MVN cells recorded showed immature forms of either the type A or the type B action potential shape. Immature type A cells had broad spontaneous spikes, and the characteristic single AHP was small in amplitude. Immature type B cells had somewhat narrower spontaneous spikes that were followed by a delayed, apamin-sensitive AHP. The delayed AHP was separated from the repolarisation phase of the spike by a period of isopotentiality. Over the period P10-P15, the mean resting potentials of the MVN cells became more negative, their action potential fall-times became shorter, the single AHP in type A cells became deeper, and the early fast AHP appeared in type B cells. Until P15 cells of varying degrees of electrophysiological maturity were found in the MVN but by P30 all MVN cells recorded were typical adult type A or type B cells. Exposure to the selective blocker of SK-type Ca-activated K channels, apamin (0.3 microM), induced depolarising plateaux and burst firing in immature type B cells at rest. The duration of the apamin-induced bursts and the spike frequency during the bursts were reduced but not abolished after blockade of Ca channels in Ca-free artificial cerebrospinal fluid containing Cd2+. By contrast, in mature type B cells at rest apamin selectively abolished the delayed slow AHP but did not induce bursting activity. Apamin had no effect

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

    PubMed

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

    2008-02-01

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

  6. Antisense suppression of potassium channel expression demonstrates its role in maturation of the action potential.

    PubMed

    Vincent, A; Lautermilch, N J; Spitzer, N C

    2000-08-15

    A developmental increase in delayed rectifier potassium current (I(Kv)) in embryonic Xenopus spinal neurons is critical for the maturation of excitability and action potential waveform. Identifying potassium channel genes that generate I(Kv) is essential to understanding the mechanisms by which they are controlled. Several Kv genes are upregulated during embryogenesis in parallel with increases in I(Kv) and produce delayed rectifier current when heterologously expressed, indicating that they could encode channels underlying this current. We used antisense (AS) cRNA to test the contribution of xKv3.1 to the maturation of I(Kv), because xKv3.1 AS appears to suppress specifically heterologous expression of potassium current by xKv3.1 mRNA. The injection of xKv3.1 AS into embryos reduces endogenous levels of xKv3.1 mRNA in the developing spinal cord and reduces the amplitude and rate of activation of I(Kv) in 40% of cultured neurons, similar to the percentage of neurons in which endogenous xKv3.1 transcripts are detected. The current in these mature neurons resembles that at an earlier stage of differentiation before the appearance of xKv3.1 mRNA. Furthermore, AS expression increases the duration of the action potential in 40% of the neurons. No change in voltage-dependent calcium current is observed, suggesting that the decrease in I(Kv) is sufficient to account for lengthening of the action potential. Computer-simulated action potentials incorporating observed reductions in amplitude and rate of activation of I(Kv) exhibit an increase in duration similar to that observed experimentally. Thus xKv3.1 contributes to the maturation of I(Kv) in a substantial percentage of these developing spinal neurons.

  7. Predictors of Generative Action among Adults in Two Transitional Countries

    ERIC Educational Resources Information Center

    Penezic, Zvjezdan; Lackovic-Grgin, Katica; Tucak, Ivana; Nekic, Marina; Zorga, Sonja; Skraban, Olga Poljsak; Vehovar, Urban

    2008-01-01

    One of the widest elaborations of generativity today is the theoretical model proposed by McAdams and de St. Aubin. This model has not yet been tested completely, that is only some of its components and their relations have been tested. The main reasons for such an empirical status of the model are inadequately clear operationalizations of the…

  8. Mobilizing Political Action on Behalf of Future Generations

    ERIC Educational Resources Information Center

    Aldy, Joseph E.

    2016-01-01

    Our failure to mobilize sufficient effort to fight climate change reflects a combination of political and economic forces, on both the national and the global level. To state the problem in its simplest terms, writes Joseph Aldy, future, unborn generations would enjoy the benefits of policies to reduce carbon emissions whereas the current…

  9. Alternatives for management of wastes generated by the formerly utilized sites remedial action program and supplement

    SciTech Connect

    Gilbert, T.L.; Peterson, J.M.; Vocke, R.W.; Alexander, J.K.

    1983-03-01

    Alternatives for disposal or stabilization of the wastes generated by the US Department of Energy's Formerly Utilized Sites Remedial Action Program (FUSRAP) are identified and compared, with emphasis on the long-term aspects. These wastes consist of soil material and rubble containing trace amounts of radionuclides. A detailed pathway analysis for the dose to the maximally exposed individual is carried out using an adaptation of the natural analogue method. Comparisons of the different alternatives, based on the results of the pathway analysis and qualitative cost considerations, indicate that, if the hazard is such that the wastes must be removed and disposed of rather than stabilized in place, disposal by immediate dispersal is preferable to containment, and containment followed by slow planned dispersal is preferable to containment without dispersal. The Supplement presents refinements of work that was reported at the 1982 International Decommissioning Symposium. The new material consists of revisions of the estimates of the predicted potential dose to the maximally exposed individual and a more detailed comparative assessment of the radiological impacts of alternatives for management of wastes generated by the US Department of Energy's Formerly Utilized Sites Remedial Action Program (FUSRAP).

  10. Differential effects of K(+) channel blockers on frequency-dependent action potential broadening in supraoptic neurons.

    PubMed

    Hlubek, M D; Cobbett, P

    2000-09-15

    Recordings were made from magnocellular neuroendocrine cells dissociated from the supraoptic nucleus of the adult guinea pig to determine the role of voltage gated K(+) channels in controlling the duration of action potentials and in mediating frequency-dependent action potential broadening exhibited by these neurons. The K(+) channel blockers charybdotoxin (ChTx), tetraethylammonium (TEA), and 4-aminopyridine (4-AP) increased the duration of individual action potentials indicating that multiple types of K(+) channel are important in controlling action potential duration. The effect of these K(+) channel blockers was almost completely reversed by simultaneous blockade of voltage gated Ca(2+) channels with Cd(2+). Frequency-dependent action potential broadening was exhibited by these neurons during trains of action potentials elicited by membrane depolarizing current pulses presented at 10 Hz but not at 1 Hz. 4-AP but not ChTx or TEA inhibited frequency-dependent action potential broadening indicating that frequency-dependent action potential broadening is dependent on increasing steady-state inactivation of A-type K(+) channels (which are blocked by 4-AP). A model of differential contributions of voltage gated K(+) channels and voltage gated Ca(2+) channels to frequency-dependent action potential broadening, in which an increase of Ca(2+) current during each successive action potential is permitted as a result of the increasing steady-state inactivation of A-type K(+) channels, is presented.

  11. The Self in Action Effects: Selective Attenuation of Self-Generated Sounds

    ERIC Educational Resources Information Center

    Weiss, Carmen; Herwig, Arvid; Schutz-Bosbach, Simone

    2011-01-01

    The immediate experience of self-agency, that is, the experience of generating and controlling our actions, is thought to be a key aspect of selfhood. It has been suggested that this experience is intimately linked to internal motor signals associated with the ongoing actions. These signals should lead to an attenuation of the sensory consequences…

  12. 2nd Generation Reusable Launch Vehicle Potential Commercial Development Scenarios

    NASA Technical Reports Server (NTRS)

    Creech, Stephen D.; Rogacki, John R. (Technical Monitor)

    2001-01-01

    The presentation will discuss potential commercial development scenarios for a Second Generation Reusable Launch Vehicle. The analysis of potential scenarios will include commercial rates of return, government return on investment, and market considerations. The presentation will include policy considerations in addition to analysis of Second Generation Reusable Launch Vehicle economics. The data discussed is being developed as a part of NASA's Second Generation Reusable Launch Vehicle Program, for consideration as potential scenarios for enabling a next generation system. Material will include potential scenarios not previously considered by NASA or presented at other conferences. Candidate paper has not been presented at a previous meeting, and conference attendance of the author has been approved by NASA.

  13. 24. DETAIL INTERIOR VIEW OF GENERATOR BUS POTENTIAL FOR UNIT ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    24. DETAIL INTERIOR VIEW OF GENERATOR BUS POTENTIAL FOR UNIT NO 1 IN BUS CELL GALLERY ON LEVEL +77 OF POWERHOUSE #1. - Bonneville Project, Powerhouse No.1, Spanning Bradford Slough, from Bradford Island, Bonneville, Multnomah County, OR

  14. Ontogeny of Vestibular Compound Action Potentials in the Domestic Chicken

    PubMed Central

    M. Jones, Sherri

    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 μV/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. PMID:11545229

  15. 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.

  16. 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,…

  17. Actionable Diagnosis of Neuroleptospirosis by Next-Generation Sequencing

    PubMed Central

    Wilson, Michael R.; Naccache, Samia N.; Samayoa, Erik; Biagtan, Mark; Bashir, Hiba; Yu, Guixia; Salamat, Shahriar M.; Somasekar, Sneha; Federman, Scot; Miller, Steve; Sokolic, Robert; Garabedian, Elizabeth; Candotti, Fabio; Buckley, Rebecca H.; Reed, Kurt D.; Meyer, Teresa L.; Seroogy, Christine M.; Galloway, Renee; Henderson, Sheryl L.; Gern, James E.; DeRisi, Joseph L.; Chiu, Charles Y.

    2014-01-01

    SUMMARY A 14-year-old boy with severe combined immunodeficiency presented three times to a medical facility over a period of 4 months with fever and headache that progressed to hydrocephalus and status epilepticus necessitating a medically induced coma. Diagnostic workup including brain biopsy was unrevealing. Unbiased next-generation sequencing of the cerebrospinal fluid identified 475 of 3,063,784 sequence reads (0.016%) corresponding to leptospira infection. Clinical assays for leptospirosis were negative. Targeted antimicrobial agents were administered, and the patient was discharged home 32 days later with a status close to his premorbid condition. Polymerase-chain-reaction (PCR) and serologic testing at the Centers for Disease Control and Prevention (CDC) subsequently confirmed evidence of Leptospira santarosai infection. PMID:24896819

  18. Hydrogen peroxide decelerates recovery of action potential after high-frequency fatigue in skeletal muscle.

    PubMed

    Oba, T; Ishikawa, T; Takaishi, T; Aoki, T; Yamaguchi, M

    2000-10-01

    Effects of reactive oxygen species (ROS), especially hydrogen peroxide (H(2)O(2)), on recovery of action potential by resting for 30 min after high-frequency fatigue were studied using frog skeletal muscle fibers. After stimulation at a frequency of 50 HZ for 2 min, the action potential amplitude was decreased by 14.5 mV from controls, and resting membrane was depolarized by 15.4 mV. Action potential duration was also prolonged by high-frequency stimulation (1.5 ms in controls to 2.6 ms). The high-frequency stimulation used here caused no muscle damage. The action potential was partially improved after a 30-min rest. Addition of catalase at 500 units/ml or H(2)O(2) at 0.5 mM to sartorius muscle did not alter any of the parameters of the action potential after high-frequency stimulation. Treatment with catalase accelerated post-fatigue recovery of the action potential. Application of H(2)O(2) delayed post-fatigue recovery of resting and action potentials. When added to detubulated toe muscle fibers, catalase no longer improved the attenuation of action potential induced by high-frequency stimulation, even after a 30-min rest. These findings suggest that removal of H(2)O(2) from transverse tubules is effective for post-fatigue recovery of action potential in skeletal muscle.

  19. Spikelets in Pyramidal Neurons: Action Potentials Initiated in the Axon Initial Segment That Do Not Activate the Soma

    PubMed Central

    Michalikova, Martina; Kempter, Richard

    2017-01-01

    Spikelets are small spike-like depolarizations that can be measured in somatic intracellular recordings. Their origin in pyramidal neurons remains controversial. To explain spikelet generation, we propose a novel single-cell mechanism: somato-dendritic input generates action potentials at the axon initial segment that may fail to activate the soma and manifest as somatic spikelets. Using mathematical analysis and numerical simulations of compartmental neuron models, we identified four key factors controlling spikelet generation: (1) difference in firing threshold, (2) impedance mismatch, and (3) electrotonic separation between the soma and the axon initial segment, as well as (4) input amplitude. Because spikelets involve forward propagation of action potentials along the axon while they avoid full depolarization of the somato-dendritic compartments, we conjecture that this mode of operation saves energy and regulates dendritic plasticity while still allowing for a read-out of results of neuronal computations. PMID:28068338

  20. On the excitation of action potentials by protons and its potential implications for cholinergic transmission.

    PubMed

    Fillafer, Christian; Schneider, Matthias F

    2016-03-01

    One of the most conserved mechanisms for transmission of a nerve pulse across a synapse relies on acetylcholine (ACh). Ever since the Nobel Prize-winning works of Dale and Loewi, it has been assumed that ACh-subsequent to its action on a postsynaptic cell-is split into inactive by-products by acetylcholinesterase (AChE). Herein, the widespread assumption of inactivity of ACh's hydrolysis products is falsified. Excitable cells (Chara braunii internodes), which had previously been unresponsive to ACh, became ACh-sensitive in the presence of AChE. The latter was evidenced by a striking difference in cell membrane depolarization upon exposure to 10 mM intact ACh (∆V = -2 ± 5 mV) and its hydrolysate (∆V = 81 ± 19 mV), respectively, for 60 s. This pronounced depolarization, which also triggered action potentials, was clearly attributed to one of the hydrolysis products: acetic acid (∆V = 87 ± 9 mV at pH 4.0; choline ineffective in the range 1-10 mM). In agreement with our findings, numerous studies in the literature have reported that acids excite gels, lipid membranes, plant cells, erythrocytes, as well as neurons. Whether excitation of the postsynaptic cell in a cholinergic synapse is due to protons or due to intact ACh is a most fundamental question that has not been addressed so far.

  1. Self-Action of Second Harmonic Generation and Longitudinal Temperature Gradient in Nonlinear-Optical Crystals

    NASA Astrophysics Data System (ADS)

    Baranov, A. I.; Konyashkin, A. V.; Ryabushkin, O. A.

    2015-09-01

    Model of second harmonic generation with thermal self-action was developed. Second harmonic generation temperature phase matching curves were measured and calculated for periodically polled lithium niobate crystal. Both experimental and calculated data show asymmetrical shift of temperature tuning curves with pump power.

  2. Ionic differences between somatic and axonal action potentials in snail giant neurones

    PubMed Central

    Wald, Flora

    1972-01-01

    1. The ionic requirements of the somatic and axonal action potentials of `H' neurones of the snail Cryptomphallus aspersa were studied using intracellular micro-electrodes. 2. The overshoot of the somatic action potential increased by 10 mV for a tenfold increase in [Ca2+]o. In calcium-free media the action potential decreased gradually to values of 50 to 90% of the control and they could be completely eliminated with 2 mM-EGTA. The maximum rate of rise also varied with [Ca2+]o. 3. After 2 hr in sodium-free solution the somatic action potential decreased 6% in overshoot and 24% in rate of rise. 4. The somatic action potential was not affected by TTX, 5 × 10-6 g/ml. Procaine, 18 mM, reduced its rate of rise but did not eliminate it whereas 30 mM-CoCl2 did. 5. The size of the axonal action potential increased with increased [Na+]o, but decreased with an increase in [Ca2+]o. 6. Procaine, 18 mM, abolished the axonal action potential whereas it was not affected by TTX, 5 × 10-6 g/ml., nor, usually, by 30 mM-CoCl2. 7. The results obtained by studying the compound action potential of the nerves were similar to those from axonal action potentials. 8. The possibility that the somatic action potential is mainly calcium dependent while the axonal action potential is mainly produced by sodium is discussed. PMID:5014099

  3. Potential effects of intrinsic heart pacemaker cell mechanisms on dysrhythmic cardiac action potential firing

    PubMed Central

    Yaniv, Yael; Tsutsui, Kenta; Lakatta, Edward G.

    2015-01-01

    The heart's regular electrical activity is initiated by specialized cardiac pacemaker cells residing in the sinoatrial node. The rate and rhythm of spontaneous action potential firing of sinoatrial node cells are regulated by stochastic mechanisms that determine the level of coupling of chemical to electrical clocks within cardiac pacemaker cells. This coupled-clock system is modulated by autonomic signaling from the brain via neurotransmitter release from the vagus and sympathetic nerves. Abnormalities in brain-heart clock connections or in any molecular clock activity within pacemaker cells lead to abnormalities in the beating rate and rhythm of the pacemaker tissue that initiates the cardiac impulse. Dysfunction of pacemaker tissue can lead to tachy-brady heart rate alternation or exit block that leads to long atrial pauses and increases susceptibility to other cardiac arrhythmia. Here we review evidence for the idea that disturbances in the intrinsic components of pacemaker cells may be implemented in arrhythmia induction in the heart. PMID:25755643

  4. [Phenibut potentiation of the therapeutic action of antiparkinson agents].

    PubMed

    Gol'dblat, Iu V; Lapin, I P

    1986-01-01

    It was observed in experiments on mice that the central action of phenibut (beta-phenyl-gamma-aminobutyric acid) diminished after destruction of brain dopaminergic neurons by 6-hydroxydopamine and after pretreatment with the dopamine receptor blocker haloperidol which suggests the dopaminergic component in the action of phenibut. In 13 of 16 patients receiving long-term treatment with antiparkinsonic drugs, addition of phenibut (0.25 g thrice daily for 10 days) resulted in marked clinical improvement with a significant increase of motor activity, as well as diminution of both rigidity and tremor. Follow-up showed a significant lowering of muscle tone of rigid muscles, augmentation of their strength and amplitude of movements. In 8 patients receiving phenibut without antiparkinsonic drugs the results were negligible.

  5. Calcium-Activated Chloride Channels (CaCCs) Regulate Action Potential and Synaptic Response in Hippocampal Neurons

    PubMed Central

    Huang, Wendy C.; Xiao, Shaohua; Huang, Fen; Harfe, Brian D.; Jan, Yuh Nung; Jan, Lily Yeh

    2012-01-01

    SUMMARY Central neurons respond to synaptic inputs from other neurons by generating synaptic potentials. Once the summated synaptic potentials reach threshold for action potential firing, the signal propagates leading to transmitter release at the synapse. The calcium influx accompanying such signaling opens calcium-activated ion channels for feedback regulation. Here we report a novel mechanism for modulating hippocampal neuronal signaling that involves calcium-activated chloride channels (CaCCs). We present the first evidence that CaCCs reside in hippocampal neurons and are in close proximity of calcium channels and NMDA receptors to shorten action potential duration, dampen excitatory synaptic potentials, impede temporal summation, and raise the threshold for action potential generation by synaptic potential. Having recently identified TMEM16A and TMEM16B as CaCCs, we further show that TMEM16B but not TMEM16A is important for hippocampal CaCC, laying the groundwork for deciphering the dynamic CaCC modulation of neuronal signaling in neurons important for learning and memory. PMID:22500639

  6. Antimalarial action of hydroxamate-based iron chelators and potentiation of desferrioxamine action by reversed siderophores.

    PubMed Central

    Golenser, J; Tsafack, A; Amichai, Y; Libman, J; Shanzer, A; Cabantchik, Z I

    1995-01-01

    Hydroxamate-based chelators of iron are potent inhibitors of in vitro growth of Plasmodium falciparum. Two types of such chelators, the natural desferrioxamine and the synthetic reversed siderophore RSFileum2, are prototypes of antimalarial agents whose action spectra differ in the speed of action, stage dependence, and degree of reversibility of effects. This work explores the possibility of improving the antimalarial efficacy of these agents by using them in various combinations on in vitro cultures of P. falciparum. Growth assessment was based both on total nucleic acid synthesis and on parasitemia. The results indicate that the synthetic reversed siderophore more than complements the antimalarial action of desferrioxamine when applied during either ring, trophozoite, or mixed stages. The combined drug effects were significantly higher than the additive effect of the individual drugs. Qualitatively similar results were obtained for both reversible effects and irreversible (i.e., sustained) effects. Following an 8-h window of exposure the combined drug treatment caused parasite growth arrest and prevented its recovery, even 3 days after the treatment. The fact that such a combination of iron chelators displays a wider action spectrum than either drug alone has implications for the design of chemotherapy regimens. PMID:7695330

  7. Action potentials and twitch forces of rabbit masseter motor units at optimum jaw angle.

    PubMed

    van Eijden, T M G J; Turkawski, S J J

    2002-08-01

    This study examines mutual correlations between electrical and contractile motor-unit properties. Action potentials and twitch force responses of 42 masseter motor units were recorded in 14 rabbits. Motor units were excited by stimulating motoneurones in the trigeminal motor nucleus. Action potentials and twitches were measured at different jaw gapes between 0 and 21 degrees, in steps of 3 degrees. For each motor unit, the jaw angle-active force interrelation was determined and variables for action potential and force were compared at the jaw angle at which the motor unit produced the largest force. The results showed a large variation in variables for action potential and force, possibly related to the variation in motor-unit morphology. A weak correlation was found between the variables for action-potential amplitude and the magnitude of optimum force, indicating that motor units producing larger forces tended to have action potentials with larger amplitudes. Twitch-contraction time and the moment arm of the motor unit correlated positively with both the median frequency and the duration of the action potential. This indicates that slower contracting motor units had longer action potentials and is in accord with the earlier observation that slower motor units are preferentially located in the anterior regions of the masseter.

  8. Correspondence between the location of evoked potential generators and sites of maximal sensitivity to stimulation.

    PubMed

    Stecker, Mark M

    2005-09-01

    The potential recorded by a set of electrodes as an action potential traverses a small axonal segment is proportional to the transmembrane potential produced during stimulation of that axon segment by the same set of recording electrodes, under certain circumstances. First, the membrane must have a constant thickness which is so small that the difference between the surface area of the inner and outer surfaces is minimal. Second, all media must be linear. Third, there must be a monotonically increasing relation between the mean transmembrane potential induced by a stimulus and the maximum transmembrane potential. Fourth, as each axon segment depolarizes, the transmembrane current and change in membrane potential during this time are same. This principle remains true for magnetic stimulation and recording as long as currents generated at the boundaries between regions of differing conductivity outside the axon contribute minimally to the field at the axon. This allows the identification of the point at which an action potential generates a maximal extracellular potential as the point that is stimulated with the lowest threshold.

  9. Prolonged modification of action potential shape by synaptic inputs in molluscan neurones.

    PubMed

    Winlow, W

    1985-01-01

    1. Somatic action potentials of Lymnaea neurons are modified by excitatory or inhibitory synaptic inputs and have been studied using phase-plane techniques and an action potential duration monitor. 2. Excitatory synaptic inputs increase the rate of neuronal discharge, cause action potential broadening, a decrease in the maximum rate of depolarization (Vd) and a decrease in the maximum rate of repolarization (Vr). 3. Inhibitory synaptic inputs decrease the discharge rate and cause narrowing of action potentials, an increase in Vd and an increase in Vr. 4. The effects reported above outlast the original synaptic inputs by many seconds and, if the somatic action potentials are similar to those in the axon terminals, they may have far-reaching effects on transmitter release.

  10. Relationships between coal properties and respirable dust generation potential

    SciTech Connect

    Srikanth, R.; Zhao, R.; Ramani, R.V.

    1995-12-31

    A two-part study was conducted to understand the factors affecting respirable dust generation potential or dustiness of coal seams. In the first part, the data from three prior comprehensive laboratory studies was analyzed to establish quantitative relationships between respirable dust generation potential and coal characteristics. This analysis indicates that respirable dust generation rate is positively correlated with Hardgrove Grindability Index. (HGI), fuel ratio (fixed carbon/volatile matter), Vitrinite Reflectance (VR), and Level of Organic Metamorphism (LOM). In the second part, specially-designed single breakage experiments were conducted to determine the primary dust generation potential of 17 coal samples obtained from four continuous miner sections, three longwall sections, and the Penn State Coal Data Bank. The single breakage study indicates that primary dust generation rate is positively correlated with fixed carbon content, fuel ratio (fixed carbon/volatile matter), VR, and LOM. Since VR and LOM are strongly influenced by the process of coalification, differences in respirable dust generation rates in different coal seams may be explained by the thermal metamorphism of sedimentary organic matter during subsurface burial.

  11. Action potentials of isolated single muscle fibers recorded by potential-sensitive dyes

    PubMed Central

    Nakajima, S.; Gilai, A.

    1980-01-01

    Light transmission changes upon massive stimulation of single muscle fibers of Xenopus were studied with the potential-sensitive nonpermeant dyes, merocyanine rhodanine (WW375) and merocyanine oxazolone (NK2367). Upon stimulation an absorption change (wave a) occurred, which probably represents the sum of action potentials in the transverse tubules and surface membrane. In WW375-stained fibers wave a is a decrease in transmission over the range of 630 to 730 nm (with NK2367, over the range of 590 to 700 nm) but becomes an increase outside this range, thus showing a triphasic spectral pattern. This spectrum differs from that of the squid axon, in which depolarization produces only an increase in transmission over the whole range of wavelengths (Ross et al. 1977. J. Membr. Biol. 33:141-183). When wave a was measured at the edge of the fiber to obtain more signal from the surface membrane, the spectrum did not seem to differ markedly from that obtained from the entire width of the fiber. Thus, the difference in the spectrum between the squid axon and the vertebrate muscle cannot be attributed to the presence of the tubular system. PMID:10822501

  12. 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.

  13. Genotoxic potential of glyphosate formulations: mode-of-action investigations.

    PubMed

    Heydens, William F; Healy, Charles E; Hotz, Kathy J; Kier, Larry D; Martens, Mark A; Wilson, Alan G E; Farmer, Donna R

    2008-02-27

    A broad array of in vitro and in vivo assays has consistently demonstrated that glyphosate and glyphosate-containing herbicide formulations (GCHF) are not genotoxic. Occasionally, however, related and contradictory data are reported, including findings of mouse liver and kidney DNA adducts and damage following intraperitoneal (ip) injection. Mode-of-action investigations were therefore undertaken to determine the significance of these contradictory data while concurrently comparing results from ip and oral exposures. Exposure by ip injection indeed produced marked hepatic and renal toxicity, but oral administration did not. The results suggest that ip injection of GCHF may induce secondary effects mediated by local toxicity rather than genotoxicity. Furthermore, these results continue to support the conclusion that glyphosate and GCHF are not genotoxic under exposure conditions that are relevant to animals and humans.

  14. Neuroactive steroids have multiple actions to potentiate GABAA receptors.

    PubMed

    Akk, Gustav; Bracamontes, John R; Covey, Douglas F; Evers, Alex; Dao, Tim; Steinbach, Joe Henry

    2004-07-01

    The effects of neuroactive steroids on the function of GABAA receptors were studied using cell-attached records of single channel activity recorded from HEK293 cells transfected with alpha1 beta2 gamma2L subunits. Activity was elicited with a half-maximal (50 microM) concentration of GABA. Two steroids were studied in detail: ACN ((3alpha,5alpha,17beta)-3-hydroxyandrostane-17-carbonitrile) and B285 ((3alpha,5beta,17beta)-3-hydroxy-18-norandrostane-17-carbonitrile). Four effects on channel activity were seen, two on open time distributions and two on closed times. When clusters of openings were elicited in the absence of steroid, the open time distribution contained three components. ACN produced concentration-dependent alterations in the open time distribution. The prevalence of the longest duration class of open times was increased from about 15% to about 40% (EC50 about 180 nM ACN), while the duration of the longest class increased from 7.4 ms to 27 ms (EC50 about 35 nM ACN). B285 also increased the prevalence of the longest duration open times (EC50 about 18 nM B285) but increased the duration only at concentrations close to 10 microM. The differences in the actions of these two steroids suggest that the effects on proportion and duration of the long duration open time component are produced by independent mechanisms and that there are separate recognition sites for the steroids which are associated with the two functional actions. The closed time distributions also showed three components in the absence of steroid. The rate of occurrence of the two brief duration closed time components decreased with increasing ACN, with an EC50 of about 50 nM ACN. In contrast, B285 did not reduce the rate of occurrence of the brief closings until high concentrations were applied. However, both B285 and ACN reduced the rate of occurrence of the activation-related closed state selectively, with comparable IC50 concentrations (about 40 nM ACN, 20 nM B285). As in the case for

  15. Molecular Action of a Potential Tumor Suppression in Mammary Carcinogenesis

    DTIC Science & Technology

    2006-05-01

    Western blotting using anti-Tid1 antibody. B, 1 day after transfection, the subconfluent transfected cells were starved overnight in DMEM containing...Hamilton, ON, Canada) provided anti-Tid1 immuno- blotting antibody. H5509 antibody, Tid1 COOH-terminus–specific antibody, was generated by immunizing...illomavirus E7 oncoprotein, RasGAP, Jak2 kinase, and HTLV -1 Tax protein (11, 18, 23, 26). Most of these molecules are known to be carcinogenic in

  16. Na+ current in presynaptic terminals of the crayfish opener cannot initiate action potentials

    PubMed Central

    2015-01-01

    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

  17. Boron-doped nanocrystalline diamond microelectrode arrays monitor cardiac action potentials.

    PubMed

    Maybeck, Vanessa; Edgington, Robert; Bongrain, Alexandre; Welch, Joseph O; Scorsone, Emanuel; Bergonzo, Philippe; Jackman, Richard B; Offenhäusser, Andreas

    2014-02-01

    The expansion of diamond-based electronics in the area of biological interfacing has not been as thoroughly explored as applications in electrochemical sensing. However, the biocompatibility of diamond, large safe electrochemical window, stability, and tunable electronic properties provide opportunities to develop new devices for interfacing with electrogenic cells. Here, the fabrication of microelectrode arrays (MEAs) with boron-doped nanocrystalline diamond (BNCD) electrodes and their interfacing with cardiomyocyte-like HL-1 cells to detect cardiac action potentials are presented. A nonreductive means of structuring doped and undoped diamond on the same substrate is shown. The resulting BNCD electrodes show high stability under mechanical stress generated by the cells. It is shown that by fabricating the entire surface of the MEA with NCD, in patterns of conductive doped, and isolating undoped regions, signal detection may be improved up to four-fold over BNCD electrodes passivated with traditional isolators.

  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. First Generation College Student Leadership Potential: A Mixed Methods Analysis

    ERIC Educational Resources Information Center

    Hojan-Clark, Jane M.

    2010-01-01

    This mixed methods research compared the leadership potential of traditionally aged first generation college students to that of college students whose parents are college educated. A college education provides advantages to those who can obtain it (Baum & Payea, 2004; Black Issues in Higher Education, 2005; Education and the Value of…

  20. Potential for wind-generated electricity in China.

    PubMed

    McElroy, Michael B; Lu, Xi; Nielsen, Chris P; Wang, Yuxuan

    2009-09-11

    Wind offers an important alternative to coal as a source of energy for generation of electricity in China with the potential for substantial savings in carbon dioxide emissions. Wind fields derived from assimilated meteorological data are used to assess the potential for wind-generated electricity in China subject to the existing government-approved bidding process for new wind farms. Assuming a guaranteed price of 0.516 RMB (7.6 U.S. cents) per kilowatt-hour for delivery of electricity to the grid over an agreed initial average period of 10 years, it is concluded that wind could accommodate all of the demand for electricity projected for 2030, about twice current consumption. Electricity available at a concession price as low as 0.4 RMB per kilowatt-hour would be sufficient to displace 23% of electricity generated from coal.

  1. Nonlinear Dynamic Modeling of Neuron Action Potential Threshold During Synaptically Driven Broadband Intracellular Activity

    PubMed Central

    Roach, Shane M.; Song, Dong; Berger, Theodore W.

    2012-01-01

    Activity-dependent variation of neuronal thresholds for action potential (AP) generation is one of the key determinants of spike-train temporal-pattern transformations from presynaptic to postsynaptic spike trains. In this study, we model the nonlinear dynamics of the threshold variation during synaptically driven broadband intracellular activity. First, membrane potentials of single CA1 pyramidal cells were recorded under physiologically plausible broadband stimulation conditions. Second, a method was developed to measure AP thresholds from the continuous recordings of membrane potentials. It involves measuring the turning points of APs by analyzing the third-order derivatives of the membrane potentials. Four stimulation paradigms with different temporal patterns were applied to validate this method by comparing the measured AP turning points and the actual AP thresholds estimated with varying stimulation intensities. Results show that the AP turning points provide consistent measurement of the AP thresholds, except for a constant offset. It indicates that 1) the variation of AP turning points represents the nonlinearities of threshold dynamics; and 2) an optimization of the constant offset is required to achieve accurate spike prediction. Third, a nonlinear dynamical third-order Volterra model was built to describe the relations between the threshold dynamics and the AP activities. Results show that the model can predict threshold accurately based on the preceding APs. Finally, the dynamic threshold model was integrated into a previously developed single neuron model and resulted in a 33% improvement in spike prediction. PMID:22156947

  2. Ozone killing action against bacterial and fungal species; microbiological testing of a domestic ozone generator.

    PubMed

    Dyas, A; Boughton, B J; Das, B C

    1983-10-01

    The action of ozone generated from a small domestic device was examined with a view to using it in clinical isolation units accommodating immunosuppressed patients. Over a six-hour period in an average size room the device did not generate sufficient ozone to suppress bacterial and fungal growth. A useful bactericidal action, against a variety of human pathogens was achieved with ozone concentrations between 0.3 to 0.9 ppm. Bactericidal ozone concentrations are close to the limit permitted for human exposure however and further experiments are indicated.

  3. 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.

  4. Gene networks activated by specific patterns of action potentials in dorsal root ganglia neurons

    PubMed Central

    Lee, Philip R.; Cohen, Jonathan E.; Iacobas, Dumitru A.; Iacobas, Sanda; Fields, R. Douglas

    2017-01-01

    Gene regulatory networks underlie the long-term changes in cell specification, growth of synaptic connections, and adaptation that occur throughout neonatal and postnatal life. Here we show that the transcriptional response in neurons is exquisitely sensitive to the temporal nature of action potential firing patterns. Neurons were electrically stimulated with the same number of action potentials, but with different inter-burst intervals. We found that these subtle alterations in the timing of action potential firing differentially regulates hundreds of genes, across many functional categories, through the activation or repression of distinct transcriptional networks. Our results demonstrate that the transcriptional response in neurons to environmental stimuli, coded in the pattern of action potential firing, can be very sensitive to the temporal nature of action potential delivery rather than the intensity of stimulation or the total number of action potentials delivered. These data identify temporal kinetics of action potential firing as critical components regulating intracellular signalling pathways and gene expression in neurons to extracellular cues during early development and throughout life. PMID:28256583

  5. Gene networks activated by specific patterns of action potentials in dorsal root ganglia neurons.

    PubMed

    Lee, Philip R; Cohen, Jonathan E; Iacobas, Dumitru A; Iacobas, Sanda; Fields, R Douglas

    2017-03-03

    Gene regulatory networks underlie the long-term changes in cell specification, growth of synaptic connections, and adaptation that occur throughout neonatal and postnatal life. Here we show that the transcriptional response in neurons is exquisitely sensitive to the temporal nature of action potential firing patterns. Neurons were electrically stimulated with the same number of action potentials, but with different inter-burst intervals. We found that these subtle alterations in the timing of action potential firing differentially regulates hundreds of genes, across many functional categories, through the activation or repression of distinct transcriptional networks. Our results demonstrate that the transcriptional response in neurons to environmental stimuli, coded in the pattern of action potential firing, can be very sensitive to the temporal nature of action potential delivery rather than the intensity of stimulation or the total number of action potentials delivered. These data identify temporal kinetics of action potential firing as critical components regulating intracellular signalling pathways and gene expression in neurons to extracellular cues during early development and throughout life.

  6. Impacts of Potential Future Droughts on Electricity Generation

    NASA Astrophysics Data System (ADS)

    Yan, E.; Wigmosta, M. S.; Tidwell, V. C.; King, C. W.

    2013-12-01

    In 2011, the state of Texas experienced the worst single-year drought on record. This recent extreme climate event raised questions as to how future droughts might impact ERCOT operations. To improve our understanding of potential risks of electricity generation curtailment due to drought, an impact analysis was performed with a series of modeling tools including climate downscaling, competitive water-use calculator, hydrologic model for various hydrologic processes, and power-plant specific models. This presentation will demonstrate the predicted effects of potential future droughts on power generation at a local level of the USGS 8-digit watersheds and power plants within the context of long-term transmission planning. The study identified three potential drought scenarios (single- and multiple-year droughts) based on historical drought records and projected climate changes from the GFDL and the PCM global climate models, for greenhouse gas emission scenarios A1B, A2, and B1 defined by the IPCC. The potential impacts under these three drought scenarios were evaluated with a hydrologic model constructed for the Texas-Gulf river basin. The Texas-Gulf hydrologic model incorporates competitive water uses, climate forcing data corresponding to each of drought scenarios, and 125 reservoirs that are currently supporting water withdrawal for various sectors and cooling water for power generation. The hydrologic responses to drought scenarios predicted for each of the USGS 8-digit watersheds (such as evapotranspiration, soil water, water yield from watersheds, stream flow, and water storage in reservoirs) provide a bases to assess if power plants potentially at risk of being of derated and watersheds are vulnerable to droughts. The key findings from this study will help to improve understanding of spatial distribution of power plants at risk and vulnerable watersheds as well as the scale of potential reduction of electricity generation. Beyond impacts to the existing

  7. Assessing Vulnerability of Electricity Generation Under Potential Future Droughts

    NASA Astrophysics Data System (ADS)

    Yan, E.; Tidwell, V. C.; Wigmosta, M. S.

    2014-12-01

    In the past few decades, the western US experienced increased sever, frequent, and prolonged droughts resulting in significant water availability issues, which raised questions as to how electricity sector might be vulnerable to future droughts. To improve our understanding of potential risks of electricity generation curtailment due to drought, an impact analysis was performed with a series of modeling tools including climate downscaling, competitive water-use calculator, hydrologic model for various hydrologic processes, and power-plant specific models. This presentation will demonstrate the predicted effects of potential droughts on power generation at a local level of the USGS 8-digit watersheds and individual power plants within the context of current and future characteristics of power system and water resource system.The study identified three potential drought scenarios based on historical drought records and projected climate changes from the GFDL and the PCM global climate models, for greenhouse gas emission scenarios A1B, A2, and B1 defined by the IPCC. The potential impacts under these three drought scenarios were evaluated with a hydrologic model constructed for the Pacific Northwest River Basin and California River Basin. The hydrologic model incorporates competitive water uses, climate forcing data corresponding to each of drought scenarios, and all major reservoirs that are currently supporting water withdrawal for various sectors and hydroelectric power generation. The hydrologic responses to drought scenarios predicted for each of the USGS 8-digit watersheds and reservoirs are used as input to power-plant specific models to quantify potential risk of curtailment at each power plant. The key findings from this study will help to improve understanding of spatial distribution of vulnerable power plants and watersheds as well as the scale of potential reduction of electricity generation under various drought scenarios. Beyond impacts to the existing

  8. Ling's Adsorption Theory as a Mechanism of Membrane Potential Generation Observed in Both Living and Nonliving Systems.

    PubMed

    Tamagawa, Hirohisa; Funatani, Makoto; Ikeda, Kota

    2016-01-26

    The potential between two electrolytic solutions separated by a membrane impermeable to ions was measured and the generation mechanism of potential measured was investigated. From the physiological point of view, a nonzero membrane potential or action potential cannot be observed across the impermeable membrane. However, a nonzero membrane potential including action potential-like potential was clearly observed. Those observations gave rise to a doubt concerning the validity of currently accepted generation mechanism of membrane potential and action potential of cell. As an alternative theory, we found that the long-forgotten Ling's adsorption theory was the most plausible theory. Ling's adsorption theory suggests that the membrane potential and action potential of a living cell is due to the adsorption of mobile ions onto the adsorption site of cell, and this theory is applicable even to nonliving (or non-biological) system as well as living system. Through this paper, the authors emphasize that it is necessary to reconsider the validity of current membrane theory and also would like to urge the readers to pay keen attention to the Ling's adsorption theory which has for long years been forgotten in the history of physiology.

  9. Analysis of long-term impacts of TRU waste remaining at generator/storage sites for No Action Alternative 2

    SciTech Connect

    Buck, J.W.; Bagaasen, L.M.; Bergeron, M.P.; Streile, G.P.

    1997-09-01

    This report is a supplement to the Waste Isolation Pilot Plant Disposal-Phase Final Supplemental Environmental Impact Statement (SEIS-II). Described herein are the underlying information, data, and assumptions used to estimate the long-term human-health impacts from exposure to radionuclides and hazardous chemicals in transuranic (TRU) waste remaining at major generator/storage sites after loss of institutional control under No Action Alternative 2. Under No Action Alternative 2, TRU wastes would not be emplaced at the Waste Isolation Pilot Plant (WIPP) but would remain at generator/storage sites in surface or near-surface storage. Waste generated at smaller sites would be consolidated at the major generator/storage sites. Current TRU waste management practices would continue, but newly generated waste would be treated to meet the WIPP waste acceptance criteria. For this alternative, institutional control was assumed to be lost 100 years after the end of the waste generation period, with exposure to radionuclides and hazardous chemicals in the TRU waste possible from direct intrusion and release to the surrounding environment. The potential human-health impacts from exposure to radionuclides and hazardous chemicals in TRU waste were analyzed for two different types of scenarios. Both analyses estimated site-specific, human-health impacts at seven major generator/storage sites: the Hanford Site (Hanford), Idaho National Engineering and Environmental Laboratory (INEEL), Lawrence Livermore National Laboratory (LLNL), Los Alamos National Laboratory (LANL), Oak Ridge National Laboratory (ORNL), Rocky Flats Environmental Technology Site (RFETS), and Savannah River Site (SRS). The analysis focused on these seven sites because 99 % of the estimated TRU waste volume and inventory would remain there under the assumptions of No Action Alternative 2.

  10. 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.

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

    PubMed

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

    2013-03-01

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

  12. A Neural Dynamic Model Generates Descriptions of Object-Oriented Actions.

    PubMed

    Richter, Mathis; Lins, Jonas; Schöner, Gregor

    2017-01-01

    Describing actions entails that relations between objects are discovered. A pervasively neural account of this process requires that fundamental problems are solved: the neural pointer problem, the binding problem, and the problem of generating discrete processing steps from time-continuous neural processes. We present a prototypical solution to these problems in a neural dynamic model that comprises dynamic neural fields holding representations close to sensorimotor surfaces as well as dynamic neural nodes holding discrete, language-like representations. Making the connection between these two types of representations enables the model to describe actions as well as to perceptually ground movement phrases-all based on real visual input. We demonstrate how the dynamic neural processes autonomously generate the processing steps required to describe or ground object-oriented actions. By solving the fundamental problems of neural pointing, binding, and emergent discrete processing, the model may be a first but critical step toward a systematic neural processing account of higher cognition.

  13. 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.

  14. 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

  15. Hybrid generative-discriminative human action recognition by combining spatiotemporal words with supervised topic models

    NASA Astrophysics Data System (ADS)

    Sun, Hao; Wang, Cheng; Wang, Boliang

    2011-02-01

    We present a hybrid generative-discriminative learning method for human action recognition from video sequences. Our model combines a bag-of-words component with supervised latent topic models. A video sequence is represented as a collection of spatiotemporal words by extracting space-time interest points and describing these points using both shape and motion cues. The supervised latent Dirichlet allocation (sLDA) topic model, which employs discriminative learning using labeled data under a generative framework, is introduced to discover the latent topic structure that is most relevant to action categorization. The proposed algorithm retains most of the desirable properties of generative learning while increasing the classification performance though a discriminative setting. It has also been extended to exploit both labeled data and unlabeled data to learn human actions under a unified framework. We test our algorithm on three challenging data sets: the KTH human motion data set, the Weizmann human action data set, and a ballet data set. Our results are either comparable to or significantly better than previously published results on these data sets and reflect the promise of hybrid generative-discriminative learning approaches.

  16. Cloud-generated radiative heating and its generation of available potential energy

    NASA Technical Reports Server (NTRS)

    Stuhlmann, R.; Smith, G. L.

    1989-01-01

    The generation of zonal available potential energy (APE) by cloud radiative heating is discussed. The APE concept was mathematically formulated by Lorenz (1955) as a measure of the maximum amount of total potential energy that is available for conversion by adiabatic processes to kinetic energy. The rate of change of APE is the rate of the generation of APE minus the rate of conversion between potential and kinetic energy. By radiative transfer calculations, a mean cloud-generated radiative heating for a well defined set of cloud classes is derived as a function of cloud optical thickness. The formulation is suitable for using a general cloud parameter data set and has the advantage of taking into account nonlinearities between the microphysical and macrophysical cloud properties and the related radiation field.

  17. Antioxidant properties of melatonin and its potential action in diseases.

    PubMed

    Karaaslan, Cigdem; Suzen, Sibel

    2015-01-01

    In recent years, relationship between free radicals and oxidative stress with aging, cancer, atherosclerosis, neurodegenerative disorders, diabetes, and inflammatory diseases became increasingly clear. Confirming the role of oxidants in numerous pathological conditions such as cancer, the antioxidants developed as therapeutics have been proven ineffective. It is well established that melatonin (MLT) and its metabolites are able to function as endogenous free-radical scavengers and broadspectrum antioxidants. Numerous studies also proved the role of MLT and its derivatives in many physiological processes and therapeutic functions, such as the regulation of circadian rhythm and immune functions. The aim of this review is to arouse attention to MLT as a potentially valuable agent in the prevention and/or treatment of some diseases.

  18. Wheel-running exercise alters rat diaphragm action potentials and their regulation by K+ channels.

    PubMed

    Van Lunteren, Erik; Moyer, Michelle

    2003-08-01

    Endurance exercise modifies regulatory systems that control skeletal muscle Na+ and K+ fluxes, in particular Na+-K+-ATPase-mediated transport of these ions. Na+ and K+ ion channels also play important roles in the regulation of ionic movements, specifically mediating Na+ influx and K+ efflux that occur during contractions resulting from action potential depolarization and repolarization. Whether exercise alters skeletal muscle electrophysiological properties controlled by these ion channels is unclear. The present study tested the hypothesis that endurance exercise modifies diaphragm action potential properties. Exercised rats spent 8 wk with free access to running wheels, and they were compared with sedentary rats living in conventional rodent housing. Diaphragm muscle was subsequently removed under anesthesia and studied in vitro. Resting membrane potential was not affected by endurance exercise. Muscle from exercised rats had a slower rate of action potential repolarization than that of sedentary animals (P = 0.0098), whereas rate of depolarization was similar in the two groups. The K+ channel blocker 3,4-diaminopyridine slowed action potential repolarization and increased action potential area of both exercised and sedentary muscle. However, these effects were significantly smaller in diaphragm from exercised than sedentary rats. These data indicate that voluntary running slows diaphragm action potential repolarization, most likely by modulating K+ channel number or function.

  19. Novel actions of next-generation taxanes benefit advanced stages of prostate cancer

    PubMed Central

    de Leeuw, Renée; Berman-Booty, Lisa D; Schiewer, Matthew J; Ciment, Stephen J; Den, Robert B; Dicker, Adam P; Kelly, William K; Trabulsi, Edouard J; Lallas, Costas D; Gomella, Leonard G; Knudsen, Karen E

    2014-01-01

    Purpose To improve the outcomes of patients with castrate resistant prostate cancer (CRPC), there is an urgent need for more effective therapies and approaches that individual specific treatments for patients with CRPC. The current studies compared the novel taxane, cabazitaxel with the previous generation docetaxel, and aimed to determine which tumors are most likely to respond. Experimental design Cabazitaxel (CBTX) and docetaxel (DCTX) were compared via in vitro modeling to determine molecular mechanism, biochemical and cell biological impact, and cell proliferation, which was further assessed ex vivo in human tumor explants. Isogenic pairs of RB knockdown and control cells were interrogated in vitro, and in xenograft tumors for cabazitaxel response. Results The data herein show that i. CBTX exerts stronger cytostatic and cytotoxic response compared to DCTX, especially in CRPC; ii. CBTX induces aberrant mitosis, leading to pyknotic and multinucleated cells; iii. taxanes do not act through the androgen receptor (AR); iv. Gene expression profiling reveals distinct molecular actions for CBTX v. tumors that have progressed to castration resistance via loss of RB show enhanced sensitivity to CBTX. Conclusions CBTX not only induces improved cytostatic and cytotoxic effects, but also impacts distinct molecular pathways, compared to DCTX, which could underlie its efficacy after DCTX treatment has failed in CRPC patients. Finally, RB is identified as the first potential biomarker that could define the therapeutic response to taxanes in metastatic CRPC. This would suggest that loss of RB function induces sensitization taxanes, which could benefit up to 50% of CRPC cases. PMID:25691773

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

    PubMed

    deCharms, R C; Merzenich, M M

    1996-06-13

    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 synchronized, which could be involved in 'binding' together individual firing-rate feature representations into a unified object percept. 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 systemically signal stimulus features, it is topographically mapped, and it follows the stimulus time course even where mean firing rate does not.

  1. Axon initial segment Kv1 channels control axonal action potential waveform and synaptic efficacy.

    PubMed

    Kole, Maarten H P; Letzkus, Johannes J; Stuart, Greg J

    2007-08-16

    Action potentials are binary signals that transmit information via their rate and temporal pattern. In this context, the axon is thought of as a transmission line, devoid of a role in neuronal computation. Here, we show a highly localized role of axonal Kv1 potassium channels in shaping the action potential waveform in the axon initial segment (AIS) of layer 5 pyramidal neurons independent of the soma. Cell-attached recordings revealed a 10-fold increase in Kv1 channel density over the first 50 microm of the AIS. Inactivation of AIS and proximal axonal Kv1 channels, as occurs during slow subthreshold somatodendritic depolarizations, led to a distance-dependent broadening of axonal action potentials, as well as an increase in synaptic strength at proximal axonal terminals. Thus, Kv1 channels are strategically positioned to integrate slow subthreshold signals, providing control of the presynaptic action potential waveform and synaptic coupling in local cortical circuits.

  2. 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.

  3. The fibrogenic actions of lung fibroblast-derived urokinase: a potential drug target in IPF

    PubMed Central

    Schuliga, Michael; Jaffar, Jade; Harris, Trudi; Knight, Darryl A; Westall, Glen; Stewart, Alastair G

    2017-01-01

    The role of urokinase plasminogen activator (uPA) in idiopathic pulmonary fibrosis (IPF) remains unclear. uPA-generated plasmin has potent fibrogenic actions involving protease activated receptor-1 (PAR-1) and interleukin-6 (IL-6). Here we characterize uPA distribution or levels in lung tissue and sera from IPF patients to establish the mechanism of its fibrogenic actions on lung fibroblasts (LFs). uPA immunoreactivity was detected in regions of fibrosis including fibroblasts of lung tissue from IPF patients (n = 7). Serum uPA levels and activity were also higher in IPF patients (n = 18) than controls (n = 18) (P < 0.05), being negatively correlated with lung function as measured by forced vital capacity (FVC) %predicted (P < 0.05). The culture supernatants of LFs from IPF patients, as compared to controls, showed an increase in plasmin activity after plasminogen incubation (5–15 μg/mL), corresponding with increased levels of uPA and IL-6 (n = 5–6, P < 0.05). Plasminogen-induced increases in plasmin activity and IL-6 levels were attenuated by reducing uPA and/or PAR-1 expression by RNAi. Plasmin(ogen)-induced mitogenesis was also attenuated by targeting uPA, PAR-1 or IL-6. Our data shows uPA is formed in active regions of fibrosis in IPF lung and contributes to LF plasmin generation, IL-6 production and proliferation. Urokinase is a potential target for the treatment of lung fibrosis. PMID:28139758

  4. Epidermal Laser Stimulation of Action Potentials in the Frog Sciatic Nerve

    DTIC Science & Technology

    2008-10-01

    Laser Stimulation of Action Potentials in the Frog Sciatic Nerve Nichole M. Jindra Robert J. Thomas Human Effectiveness Directorate Directed...in the Frog Sciatic Nerve 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 62202F 6. AUTHOR(S) .Nichole M. Jindra, Robert J. Thomas, Douglas N...Alan Rice 14. ABSTRACT Measurements of laser stimulated action potentials in the sciatic nerve of leopard frogs (Rana pipiens) were made using

  5. 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

  6. Action potential broadening and frequency-dependent facilitation of calcium signals in pituitary nerve terminals.

    PubMed

    Jackson, M B; Konnerth, A; Augustine, G J

    1991-01-15

    Hormone release from nerve terminals in the neurohypophysis is a sensitive function of action potential frequency. We have investigated the cellular mechanisms responsible for this frequency-dependent facilitation by combining patch clamp and fluorimetric Ca2+ measurements in single neurosecretory terminals in thin slices of the rat posterior pituitary. In these terminals both action potential-induced changes in the intracellular Ca2+ concentration ([Ca2+]i) and action potential duration were enhanced by high-frequency stimuli, all with a frequency dependence similar to that of hormone release. Furthermore, brief voltage clamp pulses inactivated a K+ current with a very similar frequency dependence. These results support a model for frequency-dependent facilitation in which the inactivation of a K+ current broadens action potentials, leading to an enhancement of [Ca2+]i signals. Further experiments tested for a causal relationship between action potential broadening and facilitation of [Ca2+]i changes. First, increasing the duration of depolarization, either by broadening action potentials with the K(+)-channel blocker tetraethylammonium or by applying longer depolarizing voltage clamp steps, increased [Ca2+]i changes. Second, eliminating frequency-dependent changes in duration, by voltage clamping the terminal with constant duration pulses, substantially reduced the frequency-dependent enhancement of [Ca2+]i changes. These results indicate that action potential broadening contributes to frequency-dependent facilitation of [Ca2+]i changes. However, the small residual frequency dependence of [Ca2+]i changes seen with constant duration stimulation suggests that a second process, distinct from action potential broadening, also contributes to facilitation. These two frequency-dependent mechanisms may also contribute to activity-dependent plasticity in synaptic terminals.

  7. Experimental simulation of cat electromyogram: evidence for algebraic summation of motor-unit action-potential trains.

    PubMed

    Day, S J; Hulliger, M

    2001-11-01

    Prompted by the observation that the slope of the relationship between average rectified electromyography (EMG) and the ensemble activation rate of a pool of motor units progressively decreased (showing a downward nonlinearity), an experimental study was carried out to test the widely held notion that the EMG is the simple algebraic sum of motor-unit action-potential trains. The experiments were performed on the cat soleus muscle under isometric conditions, using electrical stimulation of alpha-motor axons isolated in ventral root filaments. The EMG signals were simulated experimentally under conditions where the activation of nearly the entire pool of motor units or of subsets of motor units was completely controlled by the experimenter. Sets of individual motor units or of small groups of motor units were stimulated independently, using stimulation profiles that were strictly repeatable between trials. This permitted a rigorous quantitative comparison of EMGs that were recorded during combined activation of multiple motor filaments with EMGs that were synthesized from the algebraic summation of motor unit action potential trains generated by individual nerve filaments. These were recorded separately by individually stimulating the same filaments with the same activation profiles that were employed during combined stimulation. During combined activation of up to 10 motor filaments, experimentally recorded and computationally synthesized EMGs were virtually identical. This indicates that EMG signals indeed are the outcome of the simple algebraic summation of motor-unit action-potential trains generated by concurrently active motor units. For both recorded and synthesized EMGs, it was confirmed that EMG magnitude increased nonlinearly with the ensemble activation rate of a pool of motor units. The nonlinearity was largely abolished when EMG magnitude was estimated as the sum of rectified, instead of raw, motor-unit action-potential trains. This suggests that the

  8. Conopressin affects excitability, firing, and action potential shape through stimulation of transient and persistent inward currents in mulluscan neurons.

    PubMed

    van Soest, P F; Kits, K S

    1998-04-01

    The molluscan vasopressin/oxytocin-related neuropeptide conopressin activates two persistent inward currents in neurons from the anterior lobe of the right cerebral ganglion of Lymnaea stagnalis that are involved in the control of male copulatory behavior. The low-voltage-activated (LVA) current is activated at a wide range of membrane potentials, its amplitude being only weakly voltage dependent. The high-voltage-activated (HVA) current is activated at potentials positive to -40 mV only and shows a steep voltage dependence. Occurrence of both currents varies from cell to cell, some expressing both and others only the HVA current. In most neurons that have the LVA current, a conopressin-independent persistent inward current (INSR) is found that resembles the HVA current in its voltage dependence. The functional importance of the LVA and HVA currents was studied under current-clamp conditions in isolated anterior lobe neurons. In cells exhibiting both current types, the effect of activation of the LVA current alone was investigated as follows: previously recorded LVA current profiles were injected into the neurons, and the effects were compared with responses induced by conopressin. Both treatments resulted in a strong depolarization and firing activity. No differences in firing frequency and burst duration were observed, indicating that activation of the LVA current is sufficient to evoke bursts. In cells exhibiting only the HVA current, the effect of conopressin on the response to a depolarizing stimulus was tested. Conopressin reversibly increased the number of action potentials generated by the stimulus, suggesting that the HVA current enhances excitability and counteracts accommodation. Conopressin enhanced action potential broadening during depolarizing stimuli in many neurons. Voltage-clamp experiments performed under ion-selective conditions revealed the presence of transient sodium and calcium currents. Using the action potential clamp technique, it was

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

    PubMed

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

    2008-01-15

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

  10. Effects of sparfloxacin, grepafloxacin, moxifloxacin, and ciprofloxacin on cardiac action potential duration.

    PubMed

    Patmore, L; Fraser, S; Mair, D; Templeton, A

    2000-10-20

    Fluoroquinolone antibiotics have been associated with QT prolongation following administration to humans. This study compares the effects of four fluoroquinolones, sparfloxacin, grepafloxacin, moxifloxacin and ciprofloxacin on action potential duration recorded from canine isolated cardiac Purkinje fibres. Left and right ventricular Purkinje fibres were isolated from canine hearts and continuously superfused with physiological salt solution. Action potential duration at 90% repolarization was recorded via intracellular microelectrodes. Sparfloxacin, grepafloxacin, moxifloxacin and ciprofloxacin prolonged action potential duration in a concentration dependent manner. Mean concentrations causing a 15% prolongation of action potential duration recorded at a stimulation frequency of 1 Hz were: sparfloxacin 4.2+/-0.7 microg/ml; grepafloxacin 9.3+/-0.9 microg/ml; moxifloxacin 9.9+/-1.6 microg/ml and ciprofloxacin 72.8+/-26.4 microg/ml. Prolongation was inverse frequency dependent with larger increases in action potential duration occurring when the stimulation frequency was reduced to 0.5 Hz. These results indicate that effects on action potential duration vary within this class of compound. Rank order of potency was sparfloxacin > grepafloxacin = moxifloxacin > ciprofloxacin.

  11. A Rabbit Ventricular Action Potential Model Replicating Cardiac Dynamics at Rapid Heart Rates

    PubMed Central

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

    2008-01-01

    Mathematical modeling of the cardiac action potential has proven to be a powerful tool for illuminating various aspects of cardiac function, including cardiac arrhythmias. However, no currently available detailed action potential model accurately reproduces the dynamics of the cardiac action potential and intracellular calcium (Cai) cycling at rapid heart rates relevant to ventricular tachycardia and fibrillation. The aim of this study was to develop such a model. Using an existing rabbit ventricular action potential model, we modified the L-type calcium (Ca) current (ICa,L) and Cai cycling formulations based on new experimental patch-clamp data obtained in isolated rabbit ventricular myocytes, using the perforated patch configuration at 35–37°C. Incorporating a minimal seven-state Markovian model of ICa,L that reproduced Ca- and voltage-dependent kinetics in combination with our previously published dynamic Cai cycling model, the new model replicates experimentally observed action potential duration and Cai transient alternans at rapid heart rates, and accurately reproduces experimental action potential duration restitution curves obtained by either dynamic or S1S2 pacing. PMID:18160660

  12. 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.

  13. Direct depolarization and antidromic action potentials transiently suppress dendritic IPSPs in hippocampal CA1 pyramidal cells.

    PubMed

    Morishita, W; Alger, B E

    2001-01-01

    Whole-cell current-clamp recordings were made from distal dendrites of rat hippocampal CA1 pyramidal cells. Following depolarization of the dendritic membrane by direct injection of current pulses or by back-propagating action potentials elicited by antidromic stimulation, evoked gamma-aminobutyric acid-A (GABA(A)) receptor-mediated inhibitory postsynaptic potentials (IPSPs) were transiently suppressed. This suppression had properties similar to depolarization-induced suppression of inhibition (DSI): it was enhanced by carbachol, blocked by dendritic hyperpolarization sufficient to prevent action potential invasion, and reduced by 4-aminopyridine (4-AP) application. Thus DSI or a DSI-like process can be recorded in CA1 distal dendrites. Moreover, localized application of TTX to stratum pyramidale blocked somatic action potentials and somatic IPSPs, but not dendritic IPSPs or DSI induced by direct dendritic depolarization, suggesting DSI is expressed in part in the dendrites. These data extend the potential physiological roles of DSI.

  14. The Flash-Triggering Action Potential of the Luminescent Dinoflagellate Noctiluca

    PubMed Central

    Eckert, Roger; Sibaoka, Takao

    1968-01-01

    The action potential which elicits luminescence in Noctiluca is recorded from the flotation vacuole as a transient all-or-none hyperpolarization in response to either local or general application of inward (bath to vacuole) current. Experiments were performed to determine whether the unorthodox polarities of both the stimulus current and the potential response resulted from uncommon bioelectric mechanisms or from special morphological features of this species. The findings all indicate that the action potential belongs to the familiar class of responses which have their origin in voltage- and time-dependent selective increases in membrane permeability, and that morphological factors account for the observed deviations from normal behavior. Both the stimulus and the response have orthodox polarities provided the vacuole is designated as an "external" extracytoplasmic compartment. Differential recording between vacuole and cytoplasm showed that the action potential occurs across the vacuolar membrane, with the cytoplasmic potential, which at rest is negative with respect to the vacuole, overshooting zero and reversing sign to become transiently electropositive. The rising phase of the action potential therefore depends on active current flow through the vacuolar membrane from the vacuole into the cytoplasm. Propagation of the action potential over the subspherical cell from the locus of stimulation is thought to depend largely on the core conductor properties of the thin perivacuolar shell of cytoplasm which is bounded on its inner surface by the excitable membrane and on its outer surface by inexcitable membranes. PMID:5672004

  15. Potential for electricity generation from biomass residues in Cuba

    SciTech Connect

    Lora, E.S.

    1995-11-01

    The purpose of this paper is the study of the availability of major biomass residues in Cuba and the analysis of the electricity generation potential by using different technologies. An analysis of the changes in the country`s energy balance from 1988 up to date is presented, as well as a table with the availability study results and the energy equivalent for the following biomass residues: sugar cane bagasse and trash, rice and coffee husk, corn an cassava stalks and firewood. A total equivalent of 4.42 10{sup 6} tons/year of fuel-oil was obtained. Possible scenarios for the electricity production increase in the sugar industry are presented too. The analysis is carried out for a high stream parameter CEST and two BIG/GT system configurations. Limitations are introduced about the minimal milling capacity of the sugar mills for each technology. The calculated {open_quotes}real{close_quotes} electricity generation potential for BIG/GT systems, based on GE LM5000 CC gas turbines, an actual cane harvest of 58.0 10{sup 6} tons/year, half the available trash utilization and an specific steam consumption of 210 kg/tc, was 18601,0 GWh/year. Finally different alternatives are presented for low-scale electricity generation based on the other available agricultural residues.

  16. Exploration of Similarity Renormalization Group Generators in 1-Dimensional Potentials

    NASA Astrophysics Data System (ADS)

    Heinz, Matthias

    2016-09-01

    The Similarity Renormalization Group (SRG) is used in nuclear theory to decouple high- and low-momentum components of potentials to improve convergence and thus reduce the computational requirements of many-body calculations. The SRG is a series of unitary transformations defined by a differential equation for the Hamiltonian. The user input into the SRG evolution is a matrix called the generator, which determines to what form the Hamiltonian is transformed. As it is currently used, the SRG evolves Hamiltonian into a band diagonal form. However, due to many-body forces induced by the evolution, the SRG introduces errors when used to renormalize many-body potentials. This makes it unfit for calculations with nuclei larger than a certain size. A recent paper suggests that alternate generators may induce smaller many-body forces. Smaller many-body force induction would allow SRG use to be extended to larger nuclei. I use 1-dimensional systems of two, three, and four bosons to further study the SRG evolution and how alternate generators affect many-body forces induced.

  17. On the turbulence generated by the potential surface waves

    NASA Astrophysics Data System (ADS)

    Benilov, A. Y.

    2012-11-01

    The turbulence (the random vortex motions) of the upper ocean is nourished by the energy and momentum of the surface waves (the potential motion). The statistical characteristics of the turbulence (turbulent kinetic energy, dissipation rate, and Reynolds stresses) depend on the state of the ocean surface waves. This paper discusses the possibilities of generating this turbulence using the vortex instability of the potential surface waves. The vortex component of fluctuations of velocity field and possibly the interaction between both the vortex and potential motions cause the vertical transport of the momentum. The Reynolds tensor is a linear function of the correlation tensor of vortex field. The initial small vortex perturbations always exist in the upper ocean because of the molecular viscosity influences, especially near the free surface, and the fluctuations of the seawater density. The horizontal inhomogeneities of the seawater density produce the vortex field even if the initial vorticity was zero and the initial flow was the potential flow. The evolution of the small initial vortex disturbances in the velocity field of potential linear surface waves is reduced to a coupled set of linear ordinary differential equations of the first order with periodic coefficients. The solution of this problem shows that the small initial vortex perturbations of potential linear surface waves always grow. The initial small vortex perturbations interacting with the potential surface wave produce the small-scale turbulence (Novikov's turbulence) that finally causes the viscous dissipation of the potential surface wave. The wave-induced turbulence can be considered as developed turbulence with a well distinguishable range of the turbulent wave numberskwhere turbulence obeys the Kolmogorov's self-similarity law.

  18. Cellular uncoupling can unmask dispersion of action potential duration in ventricular myocardium. A computer modeling study.

    PubMed

    Lesh, M D; Pring, M; Spear, J F

    1989-11-01

    Although slow conduction is a requirement for the preparation of sustained reentry, it alone is not sufficient for the initiation of reentry. Additionally, unidirectional block and recovery of excitability distal to the site of block must occur. Thus, a comprehensive description of the electrophysiological determinants of reentry must explain both slow conduction and unidirectional block. Although there is a growing body of research exploring the influence of axial resistivity and anisotropy on slow conduction, somewhat less is known about the relation of axial resistivity to spatial dispersion of action potential duration, a condition favorable to the development of unidirectional block. We hypothesized that when cells are well coupled, local differences in intrinsic action potential duration are not evident and that, as axial resistivity increases, local variation in action potential duration becomes manifest. We tested this hypothesis in a numerical model of electrical propagation in a grid of resistively coupled ionic current sources simulating a sheet of ventricular myocardium. Spatial dispersion of intrinsic action potential duration was simulated by varying the magnitude of the fully activated slow inward conductance in Beeler-Reuter membrane ionic kinetics. By then altering coupling resistance, we showed that dispersion of manifest action potential duration is masked in the setting of normal low-resistance cellular coupling and unmasked by increased axial resistance. When nonuniform anisotropy was simulated, dramatic pacing-site-dependent changes in both the pattern of activation and dispersion of action potential duration were noted. These findings may be important in understanding the mechanism of reentrant tachycardia initiation in the border zone of chronic, healed myocardial infarctions where evidence suggests that abnormal cellular coupling is the predominant electrophysiological derangement. In this study, we have shown, using a detailed ionic

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

    PubMed Central

    Casale, Amanda E.; McCormick, David A.

    2012-01-01

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

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

    PubMed

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

    2017-06-01

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

  1. Evaluation of UV-radiation induced singlet oxygen generation potential of selected drugs.

    PubMed

    Pandey, R; Mehrotra, S; Ray, R S; Joshi, P C; Hans, R K

    2002-05-01

    Photosensitization reaction of drugs leading to the formation of reactive oxygen species under ultraviolet radiation (UVR) can cause tissue injury, resulting in damage to various cellular macromolecules. The aim of this study was to determine the singlet oxygen generation potential of some commonly used antibiotics so that due precautions can be exercised to minimize their photosensitizing action and oxidative stress potential. The selected antibiotics were examined for their ability to produce singlet oxygen (1O2) under artificial UVA (320-400 nm). Singlet oxygen generation of various screened antibiotics under UVA is of the following order: Nalidixic acid > Amphotericin-B > Cephradine > Cefazolin > Nafcillin > Cephalothin > Ampicillin > Cephalexin > Puromycin > Kanamycin > Lincomycin > Tetracycline > Nystatin > Gentamicin sulphate. Nalidixic acid, the most potent generator of 1O2 among the screened antibiotics, was selected to carry out further studies. Certain specific quenchers of 1O2 such as beta-carotene, 1,4-diazabicyclo[2.2.2] octane (DABCO), and sodium azide (NaN3) accorded significant inhibition in the production of 1O2. The results suggest that precautions are necessary to avoid ultraviolet radiation after the intake of photoreactive drugs, especially in tropical countries such as India. These findings are significant because UVB radiation is reportedly increasing on earth surface in part due to depletion of stratospheric ozone layer. The selected drugs are commonly used for the treatment of various diseases. Thus, the synergistic action of both can lead to undesirable phototoxic responses.

  2. Extracellular calcium transients and action potential configuration changes related to post-stimulatory potentiation in rabbit atrium.

    PubMed

    Hilgemann, D W

    1986-05-01

    Extracellular calcium transients were monitored with 2 mM tetramethylmurexide at low calcium (250 microM total, 130 microM free), and action potentials were monitored together with developed tension at normal calcium (1.3 mM) during the production and decay of post-stimulatory potentiation in rabbit left atrial strips. At normal calcium, the contractile potentiation produced by a brief burst of 4 Hz stimulation is lost in three to five post-stimulatory excitations, which correlate with a negative staircase of the late action potential. At low calcium, stimulation at 4 Hz for 3-8 s results in a net extracellular calcium depletion of 5-15 microM. At the subsequent potentiated contraction (1-45 s rest), total extracellular calcium increases by 4-8 microM. The contractile response at a second excitation is greatly suppressed and results in little or no further calcium shift; the sequence can be repeated immediately thereafter. Reducing external sodium to 60 mM (sucrose replacement) enhances post-rest contractions, suppresses the late action potential, nearly eliminates loss of contractility and net calcium efflux at post-rest excitations, and markedly reduces extracellular calcium depletion during rapid stimulation. 4-Aminopyridine (1 mM) markedly suppresses the rapid early repolarization of this preparation at post-rest excitations and the loss of contractility at post-rest stimulation from the rested state; during a post-stimulatory potentiation sequence at low calcium, replenishment of extracellular calcium takes several post-stimulatory excitations. Ryanodine (10 nM to 5 microM) abolishes the post-stimulatory contraction at rest periods of greater than 5 s. If the initial repolarization is rapid, ryanodine suppresses the late action potential, calcium efflux during quiescence is greatly accelerated, and subsequent excitations do not result in an accumulation of extracellular calcium. A positive staircase of the early action potential correlates with the magnitude

  3. Properties and ionic basis of the action potentials in the periaqueductal grey neurones of the guinea-pig.

    PubMed Central

    Sánchez, D; Ribas, J

    1991-01-01

    1. Action potentials of neurones of the ventral part of the guinea-pig periaqueductal grey (PAG) were studied by intracellular recording in a mesencephalic slice preparation maintained in vitro. 2. Fast spikes spontaneously fired last 2.8 +/- 0.6 ms (mean +/- S.D.) and have an amplitude of 72.3 +/- 5.3 mV (n = 28). The neurones could be antidromically activated from the neighbouring white matter and these spikes show an initial segment component that triggers the soma-dendritic spike. These two components were dissociated by hyperpolarization. Action potentials are Na+ dependent and a Ca2+ conductance is responsible for the hump on the falling phase. Hyperpolarization makes the hump disappear and a faster rate of rise and fall are seen. Accommodation of the firing threshold is observed in response to depolarizing ramps, which is eliminated with hyperpolarization. 3. High-threshold Ca2+ spikes are evoked in either Na(+)-free solution or in the presence of tetrodotoxin (TTX). These presumed dendritic action potentials display a fast repolarization and a large after-hyperpolarization (AHP) that prevent repetitive firing. This AHP is mainly generated by Ca(2+)-dependent K+ conductances. 4. The repolarization of fast action potentials depends on the activation of K+ conductances as well as a Na+ inactivation process. A fast-activated tetraethyl-ammonium (TEA)-sensitive K+ conductance, that could be Ca2+ dependent, and a K+ conductance blocked by apamin seem to be involved in the repolarization. 5. Each fast action potential is followed by a pronounced AHP with two components, an initial fast and a slow decaying phase. Membrane hyperpolarization around -60 mV eliminated the first component and the AHP acquired a plateau-like shape. At -90 mV the AHP was nullified. The slow phase was Ca2+ dependent and an apamin-sensitive K+ conductance is involved in its generation. This conductance may be active during the early part of the AHP, but a fast-activated TEA-sensitive K

  4. Frequency-dependent action potential prolongation in Aplysia pleural sensory neurones.

    PubMed

    Edstrom, J P; Lukowiak, K D

    1985-10-01

    The effects of repetitive activity on action-potential shape in Aplysia californica pleural sensory cells are described. Action potentials were evoked by intracellular current injection at frequencies between 7.41 and 0.2 Hz. In contrast to other molluscan neurons having brief action potentials, it was found that at these firing rates the normally brief action potential develops a prominent shoulder or plateau during the repolarization phase. Higher stimulus rates broaden the action potential more rapidly and to a greater extent than lower stimulus rates. Inactivation is slow relative to activation; effects of 3-s 6-Hz trains are detectable after 1 min rest. The amplitude of the plateau voltage reaches a maximum of 50-70 mV at the highest stimulus rates tested. Frequency-dependent increases in action-potential duration measured at half-amplitude normally range between 6 and 15 ms. Cadmium, at concentrations between 0.05 and 0.5 mM, antagonizes frequency-dependent broadening. The increases in duration induced by repetitive activity are more sensitive to cadmium than are the increases in plateau amplitude. Tetraethylammonium, at concentrations between 0.5 and 10 mM, slightly increases the duration and amplitude of single action potentials. During repetitive activity at high stimulus rates the maximum duration and rate of broadening are both increased but the amplitude of the plateau potential is not affected by these tetraethylammonium concentrations. Above 10 mM, tetraethylammonium greatly increases the duration and amplitude of single action potentials as well as the rates of action-potential duration and amplitude increase during repetitive activity. These high tetraethylammonium concentrations also cause the normally smoothly increasing duration and amplitude to reach a maximum value early in a train and then decline slowly during the remainder of the train. The consequences of frequency-dependent spike broadening in these neurons have not yet been investigated

  5. Simultaneous Knee Extensor Muscle Action Induces an Increase in Voluntary Force Generation of Plantar Flexor Muscles.

    PubMed

    Suzuki, Takahito; Shioda, Kohei; Kinugasa, Ryuta; Fukashiro, Senshi

    2017-02-01

    Suzuki, T, Shioda, K, Kinugasa, R, and Fukashiro, S. Simultaneous knee extensor muscle action induces an increase in voluntary force generation of plantar flexor muscles. J Strength Cond Res 31(2): 365-371, 2017-Maximum activation of the plantar flexor muscles is required for various sporting activities that involve simultaneous plantar flexion and knee extension. During a multi-joint movement, activation of the plantar flexor muscles is affected by the activity of the knee extensor muscles. We hypothesized that coactivation of the plantar flexor muscles and knee extensor muscles would result in a higher plantar flexion torque. To test this hypothesis, 8 male volunteers performed maximum voluntary isometric action of the plantar flexor muscles with and without isometric action of the knee extensor muscles. Surface electromyographic data were collected from 8 muscles of the right lower limb. Voluntary activation of the triceps surae muscles, evaluated using the interpolated twitch technique, significantly increased by 6.4 percentage points with intentional knee extensor action (p = 0.0491). This finding is in line with a significant increase in the average rectified value of the electromyographic activity of the vastus lateralis, fibularis longus, and soleus muscles (p = 0.013, 0.010, and 0.045, respectively). The resultant plantar flexion torque also significantly increased by 11.5% of the predetermined maximum (p = 0.031). These results suggest that higher plantar flexor activation coupled with knee extensor activation facilitates force generation during a multi-joint task.

  6. Solar salt pond potential site survey for electrical power generation

    NASA Technical Reports Server (NTRS)

    Hurick, M. G.

    1982-01-01

    A solar salt gradient pond acts as a passive heat sink or thermal battery in which energy can be recovered through the conversion of thermal energy into electrical energy. Here, a condensation of a larger report that focused on the identification of potential salt gradient pond sites in the United States using in-situ resources is presented. It is shown that there are at least 24 states that lie in a primary or secondary potential site category. Fourteen states are assigned as primary states and ten are assigned as secondary. The division is subjectively based on the severity of winter weather. The most promising states are those that lie in the southern half of the country. When the primary and secondary category states are combined with the other states that may be able to support a pond, a total of 38 states exhibit the possibility of supporting power generation sites of various size.

  7. Making smart social judgments takes time: infants' recruitment of goal information when generating action predictions.

    PubMed

    Krogh-Jespersen, Sheila; Woodward, Amanda L

    2014-01-01

    Previous research has shown that young infants perceive others' actions as structured by goals. One open question is whether the recruitment of this understanding when predicting others' actions imposes a cognitive challenge for young infants. The current study explored infants' ability to utilize their knowledge of others' goals to rapidly predict future behavior in complex social environments and distinguish goal-directed actions from other kinds of movements. Fifteen-month-olds (N = 40) viewed videos of an actor engaged in either a goal-directed (grasping) or an ambiguous (brushing the back of her hand) action on a Tobii eye-tracker. At test, critical elements of the scene were changed and infants' predictive fixations were examined to determine whether they relied on goal information to anticipate the actor's future behavior. Results revealed that infants reliably generated goal-based visual predictions for the grasping action, but not for the back-of-hand behavior. Moreover, response latencies were longer for goal-based predictions than for location-based predictions, suggesting that goal-based predictions are cognitively taxing. Analyses of areas of interest indicated that heightened attention to the overall scene, as opposed to specific patterns of attention, was the critical indicator of successful judgments regarding an actor's future goal-directed behavior. These findings shed light on the processes that support "smart" social behavior in infants, as it may be a challenge for young infants to use information about others' intentions to inform rapid predictions.

  8. Unmyelinated visceral afferents exhibit frequency dependent action potential broadening while myelinated visceral afferents do not.

    PubMed

    Li, Bai-Yan; Feng, Bin; Tsu, Hwa Y; Schild, John H

    2007-06-21

    Sensory information arising from visceral organ systems is encoded into action potential trains that propagate along afferent fibers to target nuclei in the central nervous system. These information streams range from tight patterns of action potentials that are well synchronized with the sensory transduction event to irregular, patternless discharge with no clear correlation to the sensory input. In general terms these afferent pathways can be divided into unmyelinated and myelinated fiber types. Our laboratory has a long standing interest in the functional differences between these two types of afferents in terms of the preprocessing of sensory information into action potential trains (synchrony, frequency, duration, etc.), the reflexogenic consequences of this sensory input to the central nervous system and the ionic channels that give rise to the electrophysiological properties of these unique cell types. The aim of this study was to determine whether there were any functional differences in the somatic action potential characteristics of unmyelinated and myelinated vagal afferents in response to different rates of sensory nerve stimulation. Our results showed that activity and frequency-dependent widening of the somatic action potential was quite prominent in unmyelinated but not myelinated vagal afferents. Spike broadening often leads to increased influx of Ca(2+) ions that has been associated with a diverse range of modulatory mechanisms both at the cell body and central synaptic terminations (e.g. increased neurotransmitter release.) We conclude that our observations are indicative of fundamentally different mechanisms for neural integration of sensory information arising from unmyelinated and myelinated vagal afferents.

  9. Nationwide assessment of potential output from wind-powered generators

    NASA Technical Reports Server (NTRS)

    Justus, C. G.; Hargraves, W. R.; Yalcin, A.

    1976-01-01

    A method for computing the actual expected power for a wind-powered generator from a given observed speed distribution is described and applied to estimate the potential output for different locations in the continental U.S. A contour map of generator capacity factor values (fraction of the rated output realizable) is obtained for wind-powered generator systems with a cut-in speed of 3.6 m/sec and a rated speed of 8.0 m/sec, and for a unit with hypothetical values for the 1 MW class (cut-in speed, 6.7 m/sec; rated speed, 13.4 m/sec). Results indicate that in the central U.S. and in certain areas of the New England coast at a height of 61 m, over 60% of the rated output power could be obtained on an annual average. In these areas capacity factors of over 20% could be obtained with the 1MW system.

  10. Complex slow potential generators in a simplified attention paradigm.

    PubMed

    Basile, Luis F H; Brunetti, Enzo P; Pereira, José F; Ballester, Gerson; Amaro, Edson; Anghinah, Renato; Ribeiro, Pedro; Piedade, Roberto; Gattaz, Wagner F

    2006-08-01

    We have recently obtained evidence for complex multifocal, individually variable generators of slow cortical potentials, elicited during performance of visual tasks involving expecting attention, comparison and memory [Basile, L.F.H., Ballester, G., Castro, C.C., and Gattaz, W.F., 2002. Multifocal slow potential generators revealed by high-resolution EEG and current density reconstruction. Int. J. Psychophysiol., 45 (3), 227-240; Basile, L.F.H, Baldo, M.V., Castro, C.C., and Gattaz, W.F. 2003. The generators of slow potentials obtained during verbal, pictorial and spatial tasks. Int. J. Psychophysiol., 48, 55-65]. The cue-target aspect of traditional paradigms for attention studies is equivalent to 'warning S1'-'imperative S2' in slow potential designs. We simplified Posner's spatial cueing task [Posner, M.I. 1980. Orienting of attention.Q. J. Exp. Psychol. Feb;32 (1), 3-25; Posner, M.I., Snyder, C.R., Davidson, B.J. 1980. Attention and the detection of signals. J Exp Psychol. Jun; 109 (2), 160-174] to temporal cuing only, by using visual cues to indicate the mere presence, on a known central position, of the eventual target (17 ms duration, +/-0.3 degrees grey circle). We recorded slow potentials on 12 healthy subjects, by 124-channel EEG system (Neuroscan Inc.), and modeled their generators using current density reconstruction (CDR) by L(p) 1.2 norm minimization ("Curry V4.6", Neurosoft Inc.) applied to the target onset time. MRIs were obtained for each subject for constraining source models to individual brain anatomy. Average slow potentials were computed from above 60 artifact-free EEG-epochs (ISI=1.6 s, average ITI=2.5 s). We tabulated individual cortical current distributions by cytoarchitectonic area of Brodmann, after scaling into negligible, low, moderate and strong local density, based on percentile bands with respect to absolute maximum current. Despite the task's simplicity, the main result was individual variability and complexity in both scalp

  11. Photodynamic action of chlorin e6 on thymocyte plasmatic and mitochondrial membrane potentials

    NASA Astrophysics Data System (ADS)

    Gyulkhandanyan, Grigor V.

    2005-08-01

    Transmembrane potentials appear to be cell state sensitive characteristics and can give information about cell damage initial stage. Photodynamic action of the photosensitizer chlorin e6 on plasmatic and mitochondrial membrane potentials of the rat thymus lymphocytes was studied using voltage-sensitive dye rhodamine 6G. It has been revealed that mitochondrial membrane potential is more sensitive characteristic of membrane disfunction than plasmatic one at the cell photodamage.

  12. 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.

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

    PubMed

    Shneider, M N; Pekker, M

    2014-05-01

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

  14. 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.

  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. 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.

  17. 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

  18. 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

    2015-02-03

    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.

  19. 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

  20. Adhesion to carbon nanotube conductive scaffolds forces action-potential appearance in immature rat spinal neurons.

    PubMed

    Fabbro, Alessandra; Sucapane, Antonietta; 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.

  1. Perceptual learning of acoustic noise generates memory-evoked potentials.

    PubMed

    Andrillon, Thomas; Kouider, Sid; Agus, Trevor; Pressnitzer, Daniel

    2015-11-02

    Experience continuously imprints on the brain at all stages of life. The traces it leaves behind can produce perceptual learning [1], which drives adaptive behavior to previously encountered stimuli. Recently, it has been shown that even random noise, a type of sound devoid of acoustic structure, can trigger fast and robust perceptual learning after repeated exposure [2]. Here, by combining psychophysics, electroencephalography (EEG), and modeling, we show that the perceptual learning of noise is associated with evoked potentials, without any salient physical discontinuity or obvious acoustic landmark in the sound. Rather, the potentials appeared whenever a memory trace was observed behaviorally. Such memory-evoked potentials were characterized by early latencies and auditory topographies, consistent with a sensory origin. Furthermore, they were generated even on conditions of diverted attention. The EEG waveforms could be modeled as standard evoked responses to auditory events (N1-P2) [3], triggered by idiosyncratic perceptual features acquired through learning. Thus, we argue that the learning of noise is accompanied by the rapid formation of sharp neural selectivity to arbitrary and complex acoustic patterns, within sensory regions. Such a mechanism bridges the gap between the short-term and longer-term plasticity observed in the learning of noise [2, 4-6]. It could also be key to the processing of natural sounds within auditory cortices [7], suggesting that the neural code for sound source identification will be shaped by experience as well as by acoustics.

  2. 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 %.

  3. Incorporated Fish Oil Fatty Acids Prevent Action Potential Shortening Induced by Circulating Fish Oil Fatty Acids

    PubMed Central

    Ruijter, Hester M. Den; Verkerk, Arie O.; Coronel, Ruben

    2010-01-01

    Increased consumption of fatty fish, rich in omega-3-polyunsaturated fatty acids (ω3-PUFAs) reduces the severity and number of arrhythmias. Long-term ω3-PUFA-intake modulates the activity of several cardiac ion channels leading to cardiac action potential shortening. Circulating ω3-PUFAs in the bloodstream and incorporated ω3-PUFAs in the cardiac membrane have a different mechanism to shorten the action potential. It is, however, unknown whether circulating ω3-PUFAs in the bloodstream enhance or diminish the effects of incorporated ω3-PUFAs. In the present study, we address this issue. Rabbits were fed a diet rich in fish oil (ω3) or sunflower oil (ω9, as control) for 3 weeks. Ventricular myocytes were isolated by enzymatic dissociation and action potentials were measured using the perforated patch-clamp technique in the absence and presence of acutely administered ω3-PUFAs. Plasma of ω3 fed rabbits contained more free eicosapentaenoic acid (EPA) and isolated myocytes of ω3 fed rabbits contained higher amounts of both EPA and docosahexaenoic acid (DHA) in their sarcolemma compared to control. In the absence of acutely administered fatty acids, ω3 myocytes had a shorter action potential with a more negative plateau than ω9 myocytes. In the ω9 myocytes, but not in the ω3 myocytes, acute administration of a mixture of EPA + DHA shortened the action potential significantly. From these data we conclude that incorporated ω3-PUFAs into the sarcolemma and acutely administered ω3 fatty acids do not have a cumulative effect on action potential duration and morphology. As a consequence, patients with a high cardiac ω3-PUFA status will probably not benefit from short term ω3 supplementation as an antiarrhythmic therapy. PMID:21423389

  4. Selective effects of potassium elevations on glutamate signaling and action potential conduction in hippocampus.

    PubMed

    Meeks, Julian P; Mennerick, Steven

    2004-01-07

    High-frequency synaptic transmission is depressed by moderate rises in the extracellular potassium concentration ([K+]o). Previous reports have indicated that depression of action potential signaling may underlie the synaptic depression. Here, we investigated the specific contribution of K+-induced action potential changes to synaptic depression. We found that glutamatergic transmission in the hippocampal area CA1 was significantly depressed by 8-10 mM [K+]o, but that GABAergic transmission remained intact. Riluzole, a drug that slows recovery from inactivation of voltage-gated sodium channels (NaChs), interacts with subthreshold [K+]o to depress afferent volleys and EPSCs strongly. Thus, elevated [K+]o likely depresses synapses by slowing NaCh recovery from inactivation. It is unclear from previous studies whether [K+]o-induced action potential depression is caused by changes in initiation, reliability, or waveform. We investigated these possibilities explicitly. [K+]o-induced afferent volley depression was independent of stimulus strength, suggesting that changes in action potential initiation do not explain [K+]o-induced depression. Measurements of action potentials from single axons revealed that 8 mM [K+]o increased conduction failures in a subpopulation of fibers and depressed action potential amplitude in all fibers. Together, these changes quantitatively account for the afferent volley depression. We estimate that conduction failure explains more than half of the synaptic depression observed at 8 mM [K+]o, with the remaining depression likely explained by waveform changes. These mechanisms of selective sensitivity of glutamate release to [K+]o accumulation represent a unique neuromodulatory mechanism and a brake on runaway excitation.

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

    PubMed

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

    2013-06-15

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

  6. Resurgent sodium current and action potential formation in dissociated cerebellar Purkinje neurons.

    PubMed

    Raman, I M; Bean, B P

    1997-06-15

    Voltage-dependent sodium channels were studied in dissociated cerebellar Purkinje neurons from rats. In whole-cell recordings, a tetrodotoxin (TTX)-sensitive inward current was elicited when the membrane was repolarized to voltages between -60 and -20 mV after depolarizations to +30 mV long enough to produce maximal inactivation. At -40 mV, this "resurgent" current peaked in 8 msec and decayed with a time constant of 30 msec. With 50 mM sodium as a charge carrier, the resurgent current was on average approximately 120 pA. CA3 pyramidal neurons had no such current. The current may reflect recovery of inactivated channels through open states, because in Purkinje neurons (but not CA3 neurons) there was partial recovery from inactivation at -40 mV, coinciding with the rise of resurgent current. In single-channel recordings, individual channels gave openings corresponding to resurgent and conventional transient current. Action potentials were recorded from dissociated neurons under current clamp to investigate the role of the resurgent current in action potential formation. Purkinje neurons fired spontaneously at approximately 30 Hz. Hyperpolarization to -85 mV prevented spontaneous firing, and brief depolarization then induced all-or-none firing of conglomerate action potentials comprising three to four spikes. When conglomerate action potentials were used as command voltages in voltage-clamp experiments, TTX-sensitive sodium current was elicited between spikes. The falling phase of an action potential is similar to voltage patterns that activate resurgent sodium current, and thus, resurgent sodium current likely contributes to the formation of conglomerate action potentials in Purkinje neurons.

  7. 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

  8. 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.

  9. 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).

  10. Modulation of presynaptic action potential kinetics underlies synaptic facilitation of type B photoreceptors after associative conditioning in Hermissenda.

    PubMed

    Gandhi, C C; Matzel, L D

    2000-03-01

    Descriptions of conditioned response generation in Hermissenda stipulate that the synaptic interaction between type B and A photoreceptors should be enhanced after associative pairings of light and rotation. Although evidence from several laboratories has confirmed this assumption, the mechanism underlying this synaptic facilitation has not been elucidated. Here we report that in vitro conditioning (i.e., light paired with stimulation of vestibular hair cells) modifies the kinetics of presynaptic action potentials in the B photoreceptor in a manner sufficient to account for this synaptic facilitation. After paired training, we observed an increase in the duration of evoked action potentials and a decrease in the amplitude of the spike afterhyperpolarization in the B-cell. As previously reported, paired training also enhanced the excitability (i.e., input resistance and evoked spike rate) of the B photoreceptor. In a second experiment, simultaneous recordings were made in type B and A photoreceptors, and paired training was found to produce an increase in the amplitude of the IPSP in the A photoreceptor in response to an evoked spike in the B-cell. Importantly, there was no change in the initial slope of the postsynaptic IPSP in the A photoreceptor, suggesting that spike duration-independent mechanisms of neurotransmitter exocytosis or postsynaptic receptor sensitivity did not contribute to the observed synaptic facilitation. Perfusion of 4-aminopyridine (4-AP) mimicked a known effect of behavioral conditioning in that it specifically reduced the amplitude of the transient voltage-dependent K(+) current (I(A)) in the B-cell, but in addition, produced action potential broadening and synaptic facilitation that was analogous to that observed after in vitro conditioning. Finally, the effect of 4-AP on B-cell action potentials and on the postsynaptic IPSP in the A-cell was occluded by previous paired (but not unpaired) training, suggesting that the prolongation of the B

  11. Evaluation of potential runaway generation in large-tokamak disruptions

    SciTech Connect

    Fleischmann, H.H.; Zweben, S.J. . Plasma Physics Lab. Cornell Univ., Ithaca, NY . School of Applied and Engineering Physics)

    1993-06-01

    A detailed evaluation of various potential mechanisms for the generation of strong runaway beams during disruptions of largetokamak devices, including TFTR, JET, DIIID and ITER, is performed based on typical operating parameters of these devices and the presently accepted disruption model. The main results include: (1) In the existing devices, the evaporative preicer'' process by itself can lead to sizable runaway beams in disruptions of high-current-medium-to-low-ne discharges. In ITER, such runaways are expected mainly for discharges with ne values sizably smaller than the projected typical ones. (2) Runaway generation also may occur during post-thermal-quench period through the untrapping of trapped hot-thermal electrons remaining from the pre-thermal-quench plasma; this process may be directly important in particular in disruptions of high-T[sub e] discharges with details depending on the time required for reclosure of the magnetic surfaces. Both processes (1) and (2) will occur and be completed mostly during the initial few 100 [mu]sec after the thermal quench. (3) Subsequently, close collisions of runaways with cold plasma electrons generally will lead to an exponential growth ( avalanching'') of runaway populations generated by processes (1) and/or (2) and/or others; this process will be effective in particular during the current quench phase and will continue until the resulting runaway beam will carry essentially all of the remaining discharge current. In presently existing devices, possible avalanche factors of up to 10[sup 2]--10[sup 5] may be expected; in ITER, avalanche factors of up to 10[sup 10]--10[sup 15] -- if not properly suppressed -- are expected to lead to strong runaway beams in most disruptions, except those at particularly high densities. At the same time, avalanching will shift the main part of their energy spectrum down to relatively low energies around 10--20 MeV, and may sizably change the spatial distribution of the runaways.

  12. Evaluation of potential runaway generation in large-tokamak disruptions

    SciTech Connect

    Fleischmann, H.H.; Zweben, S.J. |

    1993-06-01

    A detailed evaluation of various potential mechanisms for the generation of strong runaway beams during disruptions of largetokamak devices, including TFTR, JET, DIIID and ITER, is performed based on typical operating parameters of these devices and the presently accepted disruption model. The main results include: (1) In the existing devices, the evaporative ``preicer`` process by itself can lead to sizable runaway beams in disruptions of high-current-medium-to-low-ne discharges. In ITER, such runaways are expected mainly for discharges with ne values sizably smaller than the projected typical ones. (2) Runaway generation also may occur during post-thermal-quench period through the untrapping of trapped hot-thermal electrons remaining from the pre-thermal-quench plasma; this process may be directly important in particular in disruptions of high-T{sub e} discharges with details depending on the time required for reclosure of the magnetic surfaces. Both processes (1) and (2) will occur and be completed mostly during the initial few 100 {mu}sec after the thermal quench. (3) Subsequently, close collisions of runaways with cold plasma electrons generally will lead to an exponential growth (``avalanching``) of runaway populations generated by processes (1) and/or (2) and/or others; this process will be effective in particular during the current quench phase and will continue until the resulting runaway beam will carry essentially all of the remaining discharge current. In presently existing devices, possible avalanche factors of up to 10{sup 2}--10{sup 5} may be expected; in ITER, avalanche factors of up to 10{sup 10}--10{sup 15} -- if not properly suppressed -- are expected to lead to strong runaway beams in most disruptions, except those at particularly high densities. At the same time, avalanching will shift the main part of their energy spectrum down to relatively low energies around 10--20 MeV, and may sizably change the spatial distribution of the runaways.

  13. Characterization of action potential-evoked calcium transients in mouse postganglionic sympathetic axon bundles.

    PubMed

    Jackson, V M; Trout, S J; Brain, K L; Cunnane, T C

    2001-11-15

    1. Action potential-evoked Ca(2+) transients in postganglionic sympathetic axon bundles in mouse vas deferens have been characterized using confocal microscopy and Ca(2+) imaging. 2. Axonal Ca(2+) transients were tetrodotoxin sensitive. The amplitude depended on both the frequency of stimulation and the number of stimuli in a train. 3. Removal of extracellular Ca(2+) abolished the Ca(2+) transient. Cd(2+)(100 microM) inhibited the Ca(2+) transient by 78 +/- 10 %. The N-type Ca(2+) channel blocker omega-conotoxin GVIA (0.1 microM) reduced the amplitude by -35 +/-4 %, whereas nifedipine (10 microM; L-type) and omega-conotoxin MVIIC (0.1 microM; P/Q type) were ineffective. 4. Caffeine (10 mM), ryanodine (10 microM), cyclopiazonic acid (30 microM) or CCCP (10 microM) had no detectable effects. 5. Blockade of large and small conductance Ca(2+)-dependent K+ channels with iberiotoxin (0.1 microM) and apamin (1 microM), respectively, or Ca(2+)-dependent Cl(-) channels by niflumic acid (100 microM) did not alter Ca(2+) transients. 6. In contrast, the non-specific K+ channel blockers tetraethylammonium (10 mM) and 4-aminopyridine (10 mM) markedly increased the amplitude of the Ca(2+) transient. Blockade of delayed rectifiers and A-like K+ channels, by tityustoxin-K (alpha) (0.1 microM) and pandinustoxin-K (alpha) (10 nM), respectively, also increased the Ca(2+) transient amplitude. 7. Thus, Ca(2+) transients are evoked by Na(+)-dependent action potentials in axons. These transients originate mainly from Ca(2+) entry through voltage-dependent Ca(2+) channels (80 % Cd(2+) sensitive of which 40 % was attributable to N-type). Twenty per cent of the Ca(2+) transient was not due to Ca(2+) entry through voltage-gated Ca(2+) channels. Intracellular stores and mitochondria were not involved in the generation of the transient. Ca(2+) transients are modulated by A-like K+ channels and delayed rectifiers (possibly K(V)1.2) but not by Ca(2+)-activated ion channels.

  14. 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

  15. Event-related potentials to intact and disrupted actions in children and adults

    PubMed Central

    Pace, Amy; Carver, Leslie J.; Friend, Margaret

    2013-01-01

    The current research used event-related potentials (ERPs) to investigate neurophysiological responses to intact and disrupted actions embedded within an event in children and adults. Responses were recorded as children (24-month-olds) and adults observed a relatively novel event composed of three actions. In one condition pauses were inserted at intact boundaries (i.e., at the endpoint of each action), whereas in the other condition they were inserted at breakpoints that disrupted the action (i.e., in the middle of each action). Evoked responses revealed differences across conditions in both groups; disrupted actions elicited a prolonged negative slow wave from 100 to 700 ms in children, whereas adults demonstrated two distinct negative peaks between 50–150 and 250–350 ms. These findings contribute the first electrophysiological evidence that children readily detect disruptions to ongoing events by the end of the second year, even with limited exposure to the event itself. Furthermore, they suggest that adults rely on two distinct mechanisms when processing novel events. Results are discussed in relation to the role of perceptual and conceptual levels of analysis in the development of action processing. PMID:23374603

  16. 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.

  17. Effect of thermal acclimation on action potentials and sarcolemmal K+ channels from Pacific bluefin tuna cardiomyocytes.

    PubMed

    Galli, G L J; Lipnick, M S; Block, B A

    2009-08-01

    To sustain cardiac muscle contractility relatively independent of temperature, some fish species are capable of temporarily altering excitation-contraction coupling processes to meet the demands of their environment. The Pacific bluefin tuna, Thunnus orientalis, is a partially endothermic fish that inhabits a wide range of thermal niches. The present study examined the effects of temperature and thermal acclimation on sarcolemmal K(+) currents and their role in action potential (AP) generation in bluefin tuna cardiomyocytes. Atrial and ventricular myocytes were enzymatically isolated from cold (14 degrees C)- and warm (24 degrees C)-acclimated bluefin tuna. APs and current-voltage relations of K(+) channels were measured using the whole cell current and voltage clamp techniques, respectively. Data were collected either at the cardiomyocytes' respective acclimation temperature of 14 or 24 degrees C or at a common test temperature of 19 degrees C (to reveal the effects of acclimation). AP duration (APD) was prolonged in cold-acclimated (CA) cardiomyocytes tested at 14 degrees C compared with 19 degrees C and in warm-acclimated (WA) cardiomyocytes tested at 19 degrees C compared with 24 degrees C. This effect was mirrored by a decrease in the density of the delayed-rectifier current (I(Kr)), whereas the density of the background inward-rectifier current (I(K1)) was unchanged. When CA and WA cardiomyocytes were tested at a common temperature of 19 degrees C, no significant effects of temperature acclimation on AP shape or duration were observed, whereas I(Kr) density was markedly increased in CA cardiomyocytes. I(K1) density was unaffected in CA ventricular myocytes but was significantly reduced in CA atrial myocytes, resulting in a depolarization of atrial resting membrane potential. Our results indicate the bluefin AP is relatively short compared with other teleosts, which may allow the bluefin heart to function at cold temperatures without the necessity for thermal

  18. Action potential propagation and propagation block by GABA in rat posterior pituitary nerve terminals.

    PubMed Central

    Jackson, M B; Zhang, S J

    1995-01-01

    1. A theoretical model was developed to investigate action potential propagation in posterior pituitary nerve terminals. This model was then used to evaluate the efficacy of depolarizing and shunting GABA responses on action potential propagation. 2. Experimental data obtained from the posterior pituitary with patch clamp techniques were used to derive empirical expressions for the voltage and time dependence of the nerve terminal Na+ and K+ channels. The essential structure employed here was based on anatomical and cable data from the posterior pituitary, and consisted of a long cylindrical axon (diameter, 0.5 mm) with a large spherical swelling (diameter, 4-21 mm) in the middle. 3. In the absence of an inhibitory conductance, simulated action potentials propagated with high fidelity through the nerve terminal. Swellings could block propagation, but only when sizes exceeded those observed in the posterior pituitary. Adding axonal branches reduced the critical size only slightly. These results suggested that action potentials invade the entire posterior pituitary nerve terminal in the absence of inhibition or depression. 4. The addition of inhibitory conductance to a swelling caused simulated action potentials to fail at the swelling. Depolarizing inhibitory conductances were 1.6 times more effective than shunting inhibitory conductances in blocking propagation. 5. Inhibitory conductances within the range of experimentally observed magnitudes and localized to swellings in the observed range of sizes were too weak to block simulated action potentials. However, twofold enhancement of GABA responses by neurosteroid resulted in currents strong enough to block propagation in realistic swelling sizes. 6. GABA could block simulated propagation without neurosteroid enhancement provided that GABA was present throughout a region in the order of a few hundred micrometres. For this widespread inhibition depolarizing conductance was 2.2 times more effective than shunting

  19. Waveform Similarity Analysis: A Simple Template Comparing Approach for Detecting and Quantifying Noisy Evoked Compound Action Potentials.

    PubMed

    Potas, Jason Robert; de Castro, Newton Gonçalves; Maddess, Ted; de Souza, Marcio Nogueira

    2015-01-01

    Experimental electrophysiological assessment of evoked responses from regenerating nerves is challenging due to the typical complex response of events dispersed over various latencies and poor signal-to-noise ratio. Our objective was to automate the detection of compound action potential events and derive their latencies and magnitudes using a simple cross-correlation template comparison approach. For this, we developed an algorithm called Waveform Similarity Analysis. To test the algorithm, challenging signals were generated in vivo by stimulating sural and sciatic nerves, whilst recording evoked potentials at the sciatic nerve and tibialis anterior muscle, respectively, in animals recovering from sciatic nerve transection. Our template for the algorithm was generated based on responses evoked from the intact side. We also simulated noisy signals and examined the output of the Waveform Similarity Analysis algorithm with imperfect templates. Signals were detected and quantified using Waveform Similarity Analysis, which was compared to event detection, latency and magnitude measurements of the same signals performed by a trained observer, a process we called Trained Eye Analysis. The Waveform Similarity Analysis algorithm could successfully detect and quantify simple or complex responses from nerve and muscle compound action potentials of intact or regenerated nerves. Incorrectly specifying the template outperformed Trained Eye Analysis for predicting signal amplitude, but produced consistent latency errors for the simulated signals examined. Compared to the trained eye, Waveform Similarity Analysis is automatic, objective, does not rely on the observer to identify and/or measure peaks, and can detect small clustered events even when signal-to-noise ratio is poor. Waveform Similarity Analysis provides a simple, reliable and convenient approach to quantify latencies and magnitudes of complex waveforms and therefore serves as a useful tool for studying evoked compound

  20. [Evidences of physical agents action on bone metabolism and their potential clinical use].

    PubMed

    Lirani, Ana Paula R; Lazaretti-Castro, Marise

    2005-12-01

    The action of physical agents such as low level laser therapy, low-intensity pulsed ultrasound and electrical and electromagnetic fields on bone have been often studied, showing that they are able to promote osteogenesis, accelerate fracture consolidation and augment bone mass. The use of these therapeutic modalities was first based on the finding that bone is a piezoelectric material, that means it can generate polarization when deformed, transforming mechanical energy into electric energy, and this has widen therapeutic possibilities to bony tissue. The present work aims to present evidences of physiologic effects and mechanisms of action of these physical agents on bone metabolism, based on articles published in international scientific literature.

  1. Electromagnetic fields and potentials generated by massless charged particles

    SciTech Connect

    Azzurli, Francesco; Lechner, Kurt

    2014-10-15

    We provide for the first time the exact solution of Maxwell’s equations for a massless charged particle moving on a generic trajectory at the speed of light. In particular we furnish explicit expressions for the vector potential and the electromagnetic field, which were both previously unknown, finding that they entail different physical features for bounded and unbounded trajectories. With respect to the standard Liénard–Wiechert field the electromagnetic field acquires singular δ-like contributions whose support and dimensionality depend crucially on whether the motion is (a) linear, (b) accelerated unbounded, (c) accelerated bounded. In the first two cases the particle generates a planar shock-wave-like electromagnetic field traveling along a straight line. In the second and third cases the field acquires, in addition, a δ-like contribution supported on a physical singularity-string attached to the particle. For generic accelerated motions a genuine radiation field is also present, represented by a regular principal-part type distribution diverging on the same singularity-string. - Highlights: • First exact solution of Maxwell’s equations for massless charges in arbitrary motion. • Explicit expressions of electromagnetic fields and potentials. • Derivations are rigorous and based on distribution theory. • The form of the field depends heavily on whether the motion is bounded or unbounded. • The electromagnetic field contains unexpected Dirac-delta-function contributions.

  2. 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.

  3. 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…

  4. The Transformative Potential of Action Research and ICT in the Second Language (L2) Classroom

    ERIC Educational Resources Information Center

    Farren, Margaret; Crotty, Yvonne; Kilboy, Laura

    2015-01-01

    This study shows the transformative potential of action research and information and communications technology (ICT) in the second language (L2) classroom. Two enquiries from teacher-researchers are detailed in the article. Their engagement in a collaborative professional development Masters programme was pivotal in designing and implementing ICT…

  5. 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…

  6. Generation of electrostatic drift zonal flows under the action of mean sheared flows

    NASA Astrophysics Data System (ADS)

    Kaladze, T. D.; Kharshiladze, O.

    2016-12-01

    Generation of large-scale zonal flows by the small-scale electrostatic drift wave turbulence in the magnetized plasma under the action of mean poloidal sheared flow is considered. Attention to large-scale (compared to the ion Larmor radius) drift structures is paid. To this end, the generalized Hasegawa-Mima equation containing both vector and scalar nonlinearities is derived, and the appropriate eigenvalue problem is solved numerically. Destabilizing role of the small amplitude mean shear flow and spatial inhomogeneity of electron temperature is shown.

  7. The California Climate Action Registry: Development of methodologies for calculating greenhouse gas emissions from electricity generation

    SciTech Connect

    Price, Lynn; Marnay, Chris; Sathaye, Jayant; Muritshaw, Scott; Fisher, Diane; Phadke, Amol; Franco, Guido

    2002-08-01

    The California Climate Action Registry, which will begin operation in Fall 2002, is a voluntary registry for California businesses and organizations to record annual greenhouse gas emissions. Reporting of emissions in the Registry by a participant involves documentation of both ''direct'' emissions from sources that are under the entity's control and ''indirect'' emissions controlled by others. Electricity generated by an off-site power source is considered to be an indirect emission and must be included in the entity's report. Published electricity emissions factors for the State of California vary considerably due to differences in whether utility-owned out-of-state generation, non-utility generation, and electricity imports from other states are included. This paper describes the development of three methods for estimating electricity emissions factors for calculating the combined net carbon dioxide emissions from all generating facilities that provide electricity to Californians. We find that use of a statewide average electricity emissions factor could drastically under- or over-estimate an entity's emissions due to the differences in generating resources among the utility service areas and seasonal variations. In addition, differentiating between marginal and average emissions is essential to accurately estimate the carbon dioxide savings from reducing electricity use. Results of this work will be taken into consideration by the Registry when finalizing its guidance for use of electricity emissions factors in calculating an entity's greenhouse gas emissions.

  8. Ecstasy and methamphetamine elicit action potential bursts via different mechanisms in a central snail neuron.

    PubMed

    Lin, Pei-Lin; Tsai, Ming-Cheng; Lu, Guan-Ling; Lu, Dah-Yuu; Chuang, Chieh-Min; Yang, Han-Yin; Huang, Shiang-Suo; Chen, Yi-Hung

    2010-01-01

    This study sought to determine the effects of (+) methamphetamine (METH) and its ring-substituted analog (+/-)3,4-methylenedioxymethamphetamine (MDMA; ecstasy) on electrophysiological behavior and their relationships to second messenger systems in an identifiable RP4 neuron of the African snail, Achatina fulica Ferussac. Extracellular application of MDMA at 1mM and METH at 3mM elicited action potential bursts that were not blocked after immersing the neurons in Ca(2+)-free solution. Notably, MDMA- (1mM) elicited action potential bursts were blocked by pretreatment with the protein kinase C (PKC) inhibitors chelerythrine (20 microM) and Ro 31-8220 (20 microM), but not by the PKA inhibitors KT-5720 (10 microM) and H89 (10 microM). The PKC activator phorbol 12,13-dibutyrate (PDBu; 3 microM), but not the PKA activator forskolin (50 microM), facilitated the induction of bursts elicited by MDMA at a lower concentration (0.3mM). In contrast, METH- (3mM) elicited action potential bursts were blocked by pretreatment with KT-5720 (10 microM) and H89 (10 microM), but not by chelerythrine (20 microM) and Ro 31-8220 (20 microM). Forskolin (50 microM), but not PDBu (3 microM) facilitated the induction of bursts elicited by METH at a lower concentration (1mM). Tetraethylammonium chloride (TEA), a blocker of the delayed rectifying K(+) current (I(KD)), did not elicit bursts at a concentration of 5mM but did facilitate the induction of action potential bursts elicited by both METH and MDMA. Voltage clamp studies revealed that both METH and MDMA decreased the TEA-sensitive I(KD) of the RP4 neuron. Forskolin (50 microM) or dibutyryl cAMP (1mM), a membrane-permeable cAMP analog, alone did not elicit action potential bursts. However, co-administration with forskolin (50 microM) and TEA (5mM) or co-administration with dibutyryl cAMP (1mM) and TEA (50mM) elicited action potential bursts in the presence of the PKC inhibitor chelerythrine (20 microM). Similarly, PDBu (10 microM) or phorbol

  9. Dependence of transient and residual calcium dynamics on action-potential patterning during neuropeptide secretion.

    PubMed

    Muschol, M; Salzberg, B M

    2000-09-15

    Secretion of the neuropeptide arginine vasopressin (AVP) from the neurohypophysis is optimized by short phasic bursts of action potentials with a mean intraburst frequency around 10 Hz. Several hypotheses, most prominently action-potential broadening and buildup of residual calcium, have been proposed to explain this frequency dependence of AVP release. However, how either of these mechanisms would optimize release at any given frequency remains an open question. We have addressed this issue by correlating the frequency-dependence of intraterminal calcium dynamics and AVP release during action-potential stimulation. By monitoring the intraterminal calcium changes with low-affinity indicator dyes and millisecond time resolution, the signal could be dissected into three separate components: rapid Ca(2+) rises (Delta[Ca(2+)](tr)) related to action-potential depolarization, Ca(2+) extrusion and/or uptake, and a gradual increase in residual calcium (Delta[Ca(2+)](res)) throughout the stimulus train. Action-potential stimulation modulated all three components in a manner dependent on both the stimulation frequency and number of stimuli. Overall, the cumulative Delta[Ca(2+)](tr) amplitude initially increased with f(Stim) and then rapidly deteriorated, with a maximum around f(Stim)

  10. 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

  11. Health care industries: potential generators of genotoxic waste.

    PubMed

    Sharma, Pratibha; Kumar, Manish; Mathur, N; Singh, A; Bhatnagar, P; Sogani, M

    2013-08-01

    Health care waste includes all the waste generated by health care establishments, research facilities, and laboratories. This constitutes a variety of chemical substances, such as pharmaceuticals, radionuclides, solvents, and disinfectants. Recently, scientists and environmentalists have discovered that wastewater produced by hospitals possesses toxic properties due to various toxic chemicals and pharmaceuticals capable of causing environmental impacts and even lethal effects to organisms in aquatic ecosystems. Many of these compounds resist normal wastewater treatment and end up in surface waters. Besides aquatic organisms, humans can be exposed through drinking water produced from contaminated surface water. Indeed, some of the substances found in wastewaters are genotoxic and are suspected to be potential contributors to certain cancers. The aim of this study was to evaluate the genotoxic and cytotoxic potential of wastewaters from two hospitals and three clinical diagnostic centers located in Jaipur (Rajasthan State), India using the prokaryotic Salmonella mutagenicity assay (Ames assay) and the eukaryotic Saccharomyces cerevisiae respiration inhibition assay. In the Ames assay, untreated wastewaters from both of the health care sectors resulted in significantly increased numbers of revertant colonies up to 1,000-4,050 as measured by the Salmonella typhimurium TA98 and TA100 strains (with and without metabolic activation) after exposure to undiluted samples, which indicated the highly genotoxic nature of these wastewaters. Furthermore, both hospital and diagnostic samples were found to be highly cytotoxic. Effective concentrations at which 20 % (EC20) and 50 % (EC50) inhibition of the respiration rate of the cells occurred ranged between ~0.00 and 0.52 % and between 0.005 and 41.30 % (calculated with the help of the MS excel software XLSTAT 2012.1.01; Addinsoft), respectively, as determined by the S. cerevisiae assay. The results indicated that hospital

  12. 77 FR 54619 - Exelon Generation Company, LLC., Receipt of Request for Action

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-05

    ... generators (DG) is threatened because the combustion air can be diluted with steam. Although the combustion... for the DG room. Under certain conditions, the ventilation damper alignment is such that steam that... be drawn into the engine, potentially starving the engine of air. The effects of high temperature...

  13. 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.

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

    NASA Astrophysics Data System (ADS)

    Amaral, J.; Cardoso, S.; Freitas, P. P.; Sebastião, 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 μV 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.

  15. Phorbol esters broaden the action potential in CA1 hippocampal pyramidal cells.

    PubMed

    Storm, J F

    1987-03-20

    Intracellular recordings were made from CA1 pyramidal cells in rat hippocampal slices. Single action potentials were elicited by injection of brief current pulses. Bath application of phorbol esters (4 beta-phorbol-12,13-diacetate, 0.3-5 microM; or 4 beta-phorbol-12,13-dibutyrate, 5-10 microM) broadened the action potential in each of the cells tested (n = 9). The broadening reflected slowing of the repolarization, whereas the upstroke of the spike was unchanged. This effect may enhance transmitter release from synaptic terminals, and contribute to enhancement of synaptic transmission through activation of protein kinase C, a mechanism which has been associated with long term potentiation.

  16. Harmonic development of tide-generating potential of terrestrial planets

    NASA Astrophysics Data System (ADS)

    Kudryavtsev, Sergey M.

    2008-08-01

    The aim of this study is to obtain high-accurate harmonic developments of the tide-generating potential (TGP) of Mercury, Venus and Mars. The planets’ TGP values have been first calculated on the base of DE/LE-406 numerical planetary/lunar ephemerides over a long period of time and then processed by a new spectral analysis method. According to this method the development is directly made to Poisson series where both amplitudes and arguments of the series’ terms are high-degree polynomials of time. A new harmonic development of Mars TGP is made over the time period 1900 AD 2100 AD and includes 767 second-order Poisson series’ terms of minimum amplitude equal to 10-7 m2 s-2. Analogous series composing both Mercury and Venus TGP harmonic models are built over the time period 1000 AD 3000 AD and include 1,061 and 693 terms, respectively. A modification of the standard HW95 format for representation of the terrestrial planets’ TGP is proposed. The number of terms in the planets’ TGP models transformed to the modified HW95 format is 650 for Mercury, 422 for Venus, and 480 for Mars. The quality of the new developments of the terrestrial planets’ TGP is better than that of the similar developments obtained earlier.

  17. Numerical Grid Generation and Potential Airfoil Analysis and Design

    DTIC Science & Technology

    1988-01-01

    contents include a discussion of grid generation concepts and schemes in the literature , iter- ative methods for numerical grid generation and two...to multicomponent rN airfoils, arbitrary multiple bodies and cascade grid generation for the first time. We present representative results as a... literature , iter- ative methods for numerical grid generation and two differential grid gen- eration schemes: (1) an elliptic, and (2) a parabolic scheme. A

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

    PubMed

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

    2017-03-23

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

  19. The effect of adrenaline on the temperature dependency of cardiac action potentials in pink salmon Oncorhynchus gorbuscha.

    PubMed

    Ballesta, S; Hanson, L M; Farrell, A P

    2012-04-01

    Using sharp electrode impalement, action potentials recorded from atrial and ventricular tissue of pink salmon Oncorhynchus gorbuscha generally decreased in duration with increasing test temperature (6, 10, 16 and 20° C). Stimulation of the tissue using 500 nM adrenaline had no significant effect on the duration of the atrial action potential at any test temperature but lengthened the ventricular action potential by ~17%.

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

    PubMed

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

    2013-04-26

    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 IC50 values of 1.2 and 1.5mM, 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; IC50=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.

  1. Simple techniques suitable for student use to record action potentials from the frog heart.

    PubMed

    Yoshida, S

    2001-12-01

    Demonstrating action potentials during class experiments is very educational for science students. It is not easy, however, to obtain a stable intracellular recording of action potentials from the conventionally used skeletal muscle cells, because the tip of a glass microelectrode often comes out or breaks due to muscle contraction. Here, I present a much simpler recording method using a flexible polyethylene electrode with a wide orifice (approximately 1 mm) for a bullfrog heart beating on automaticity. Extracellular recordings of action potentials (electrocardiogram) can be obtained by placing an electrode on the cardiac surface, and transmembrane potentials can be obtained by rupturing the membrane with negative pressure, i.e., whole cell configuration. Once attached to the heart by suction, the polyethylene electrode does not easily come off during contraction of the heart. Perfusion of the heart via the postcaval vein offers us opportunities for observing the effects of either changing ionic compositions of solutions or applying drugs. The techniques shown here provide a simple and convenient way to perform a variety of class experiments.

  2. Clinical next generation sequencing to identify actionable aberrations in a phase I program

    PubMed Central

    Boland, Genevieve M.; Piha-Paul, Sarina A.; Subbiah, Vivek; Routbort, Mark; Herbrich, Shelley M.; Baggerly, Keith; Patel, Keyur P.; Brusco, Lauren; Horombe, Chacha; Naing, Aung; Fu, Siqing; Hong, David S.; Janku, Filip; Johnson, Amber; Broaddus, Russell; Luthra, Raja; Shaw, Kenna; Mendelsohn, John; Mills, Gordon B.; Meric-Bernstam, Funda

    2015-01-01

    Purpose We determined the frequency of recurrent hotspot mutations in 46 cancer-related genes across tumor histologies in patients with advanced cancer. Methods We reviewed data from 500 consecutive patients who underwent genomic profiling on an IRB-approved prospective clinical protocol in the Phase I program at the MD Anderson Cancer Center. Archival tumor DNA was tested for 740 hotspot mutations in 46 genes (Ampli-Seq Cancer Panel; Life Technologies, CA). Results Of the 500 patients, 362 had at least one reported mutation/variant. The most common likely somatic mutations were within TP53 (36%), KRAS (11%), and PIK3CA (9%) genes. Sarcoma (20%) and kidney (30%) had the lowest proportion of likely somatic mutations detected, while pancreas (100%), colorectal (89%), melanoma (86%), and endometrial (75%) had the highest. There was high concordance in 62 patients with paired primary tumors and metastases analyzed. 151 (30%) patients had alterations in potentially actionable genes. 37 tumor types were enrolled; both rare actionable mutations in common tumor types and actionable mutations in rare tumor types were identified. Conclusion Multiplex testing in the CLIA environment facilitates genomic characterization across multiple tumor lineages and identification of novel opportunities for genotype-driven trials. PMID:26015395

  3. Weak action potential backpropagation is associated with high-frequency axonal firing capability in principal neurons of the gerbil medial superior olive.

    PubMed

    Scott, Luisa L; Hage, Travis A; Golding, Nace L

    2007-09-01

    Principal neurons of the medial superior olive (MSO) convey azimuthal sound localization cues through modulation of their rate of action potential firing. Previous intracellular studies in vitro have shown that action potentials appear highly attenuated at the soma of MSO neurons, potentially reflecting specialized action potential initiation and/or a physically distant site of generation. To examine this more directly, we made dual patch-clamp recordings from MSO principal neurons in gerbil brainstem slices. Using somatic and dendritic whole-cell recordings, we show that graded action potentials at the soma are highly sensitive to the rate of rise of excitation and undergo strong attenuation in their backpropagation into the dendrites (length constant, 76 microm), particularly during strong dendritic excitation. Using paired somatic whole-cell and axonal loose-patch recordings, we show that action potentials recorded in the axon at distances > 25 microm are all-or-none, and uniform in amplitude even when action potentials appear graded at the soma. This proximal zone corresponded to the start of myelination in the axon, as assessed with immunocytochemical staining for myelin basic protein in single-labelled neurons. Finally, the axon was capable of sustaining remarkably high firing rates, with perfect entrainment occurring at frequencies of up to 1 kHz. Together, our findings show that action potential signalling in MSO principal neurons is highly secure, but shows a restricted invasion of the somatodendritic compartment of the cell. This restriction may be important for minimizing distortions in synaptic integration during the high frequencies of synaptic input encountered in the MSO.

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

    PubMed

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

    2012-03-09

    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.

  5. 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

  6. 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

  7. 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

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

    PubMed Central

    Migliore, M

    1996-01-01

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

  9. Regulation of cough and action potentials by voltage-gated Na channels.

    PubMed

    Carr, Michael J

    2013-10-01

    The classical role ascribed to voltage-gated Na channels is the conduction of action potentials. Some excitable tissues such as cardiac muscle and skeletal muscle predominantly express a single voltage-gated Na channels isoform. Of the nine voltage-gated Na channels, seven are expressed in neurons, of these Nav 1.7, 1.8 and 1.9 are expressed in sensory neurons including vagal sensory neurons that innervate the airways and initiate cough. Nav 1.7 and Nav 1.9 are of particular interest as they represent two extremes in the functional diversity of voltage-gated Na channels. Voltage-gated Na channel isoforms expressed in airway sensory neurons produce multiple distinct Na currents that underlie distinct aspects of sensory neuron function. The interaction between voltage-gated Na currents underlies the characteristic ability of airway sensory nerves to encode encounters with irritant stimuli into action potential discharge and evoke the cough reflex.

  10. FHF-independent conduction of action potentials along the leak-resistant cerebellar granule cell axon

    PubMed Central

    Dover, Katarzyna; Marra, Christopher; Solinas, Sergio; Popovic, Marko; Subramaniyam, Sathyaa; Zecevic, Dejan; D'Angelo, Egidio; Goldfarb, Mitchell

    2016-01-01

    Neurons in vertebrate central nervous systems initiate and conduct sodium action potentials in distinct subcellular compartments that differ architecturally and electrically. Here, we report several unanticipated passive and active properties of the cerebellar granule cell's unmyelinated axon. Whereas spike initiation at the axon initial segment relies on sodium channel (Nav)-associated fibroblast growth factor homologous factor (FHF) proteins to delay Nav inactivation, distal axonal Navs show little FHF association or FHF requirement for high-frequency transmission, velocity and waveforms of conducting action potentials. In addition, leak conductance density along the distal axon is estimated as <1% that of somatodendritic membrane. The faster inactivation rate of FHF-free Navs together with very low axonal leak conductance serves to minimize ionic fluxes and energetic demand during repetitive spike conduction and at rest. The absence of FHFs from Navs at nodes of Ranvier in the central nervous system suggests a similar mechanism of current flux minimization along myelinated axons. PMID:27666389

  11. Tracking axonal action potential propagation on a high-density microelectrode array across hundreds of sites.

    PubMed

    Bakkum, Douglas J; Frey, Urs; Radivojevic, Milos; Russell, Thomas L; Müller, Jan; Fiscella, Michele; Takahashi, Hirokazu; Hierlemann, Andreas

    2013-01-01

    Axons are traditionally considered stable transmission cables, but evidence of the regulation of action potential propagation demonstrates that axons may have more important roles. However, their small diameters render intracellular recordings challenging, and low-magnitude extracellular signals are difficult to detect and assign. Better experimental access to axonal function would help to advance this field. Here we report methods to electrically visualize action potential propagation and network topology in cortical neurons grown over custom arrays, which contain 11,011 microelectrodes and are fabricated using complementary metal oxide semiconductor technology. Any neuron lying on the array can be recorded at high spatio-temporal resolution, and simultaneously precisely stimulated with little artifact. We find substantial velocity differences occurring locally within single axons, suggesting that the temporal control of a neuron's output may contribute to neuronal information processing.

  12. Risperidone prolongs cardiac action potential through reduction of K+ currents in rabbit myocytes.

    PubMed

    Gluais, Pascale; Bastide, Michèle; Caron, Jacques; Adamantidis, Monique

    2002-05-31

    Prolongation of QT interval by antipsychotic drugs is an unwanted side effect that may lead to ventricular arrhythmias. The antipsychotic agent risperidone has been shown to cause QT prolongation, especially in case of overdosage. We investigated risperidone effects on action potentials recorded from rabbit Purkinje fibers and ventricular myocardium and on potassium currents recorded from atrial and ventricular rabbit isolated myocytes. The results showed that (1) risperidone (0.1-3 microM) exerted potent lengthening effects on action potential duration in both tissues with higher potency in Purkinje fibers and caused the development of early afterdepolarizations at low stimulation rate; (2) risperidone (0.03-0.3 microM) reduced significantly the current density of the delayed rectifier current and at 30 microM decreased the transient outward and the inward rectifier currents. This study might explain QT prolongation observed in some patients treated with risperidone and gives enlightenment on the risk of cardiac adverse events.

  13. 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

  14. Monophasic action potentials in a patient with multiform ventricular tachycardia without QT prolongation.

    PubMed Central

    Emori, T; Ohe, T; Shimomura, K

    1993-01-01

    A 41 year old woman had multiform ventricular tachycardia without QT prolongation. Monophasic action potentials were recorded from the right ventricle during the attacks of multiform ventricular tachycardia and effective refractory periods were examined at the same sites. There was no abnormal hump to suggest early afterdepolarisation in the monophasic action potentials, but there was dispersion of the effective refractory period in the right ventricle (80 ms). Stimulation from the right ventricular apex, where the effective refractory period was shortest, reproducibly induced multiform ventricular tachycardia. Two weeks after admission, when her condition was stable, multiform ventricular tachycardia could not be induced and the dispersion of the effective refractory period in the right ventricle was 20 ms. PMID:8489870

  15. Autonomic control of cardiac action potentials: role of potassium channel kinetics in response to sympathetic stimulation.

    PubMed

    Terrenoire, Cecile; Clancy, Colleen E; Cormier, Joseph W; Sampson, Kevin J; Kass, Robert S

    2005-03-18

    I(Ks), the slowly activating component of the delayed rectifier current, plays a major role in repolarization of the cardiac action potential (AP). Genetic mutations in the alpha- (KCNQ1) and beta- (KCNE1) subunits of I(Ks) underlie Long QT Syndrome type 1 and 5 (LQT-1 and LQT-5), respectively, and predispose carriers to the development of polymorphic ventricular arrhythmias and sudden cardiac death. beta-adrenergic stimulation increases I(Ks) and results in rate dependent AP shortening, a control system that can be disrupted by some mutations linked to LQT-1 and LQT-5. The mechanisms by which I(Ks) regulates action potential duration (APD) during beta-adrenergic stimulation at different heart rates are not known, nor are the consequences of mutation induced disruption of this regulation. Here we develop a complementary experimental and theoretical approach to address these questions. We reconstituted I(Ks) in CHO cells (ie, KCNQ1 coexpressed with KCNE1 and the adaptator protein Yotiao) and quantitatively examined the effects of beta-adrenergic stimulation on channel kinetics. We then developed theoretical models of I(Ks) in the absence and presence of beta-adrenergic stimulation. We simulated the effects of sympathetic stimulation on channel activation (speeding) and deactivation (slowing) kinetics on the whole cell action potential under different pacing conditions. The model suggests these kinetic effects are critically important in rate-dependent control of action potential duration. We also investigate the effects of two LQT-5 mutations that alter kinetics and impair sympathetic stimulation of I(Ks) and show the likely mechanism by which they lead to tachyarrhythmias and indicate a distinct role of I(KS) kinetics in this electrical dysfunction. The full text of this article is available online at http://circres.ahajournals.org.

  16. SHAPING OF ACTION POTENTIALS BY TYPE I AND TYPE II BK CHANNELS

    PubMed Central

    Jaffe, David B.; Wang, Bin; Brenner, Robert

    2011-01-01

    The BK channel is a Ca2+ and voltage-gated conductance responsible for shaping action potential waveforms in many types of neurons. Type II BK channels are differentiated from type I channels by their pharmacology and slow gating kinetics. The β4 accessory subunit confers type II properties on BK α subunits. Empirically derived properties of BK channels, with and without the β4 accessory subunit, were obtained using a heterologous expression system under physiological ionic conditions. These data were then used to study how BK channels alone (type I) and with the accessory β4 subunit (type II) modulate action potential properties in biophysical neuron models. Overall, the models support the hypothesis that it is the slower kinetics provided by the β4 subunit that endows the BK channel with type II properties, which leads to broadening of action potentials and, secondarily, to greater recruitment of SK channels reducing neuronal excitability. Two regions of parameter space distinguished type II and type I effects; one where the range of BK-activating Ca2+ was high (>20 µM) and the other where BK-activating Ca2+ was low (~0.4–1.2 µM). The latter required an elevated BK channel density, possibly beyond a likely physiological range. BK-mediated sharpening of the spike waveform associated with the lack of the β4 subunit was sensitive to the properties of voltage-gated Ca2+ channels due to electrogenic effects on spike duration. We also found that depending on Ca2+ dynamics, type II BK channels may have the ability to contribute to the medium AHP, a property not generally ascribed to BK channels, influencing the frequency-current relationship. Finally, we show how the broadening of action potentials conferred by type II BK channels can also indirectly increase the recruitment of SK-type channels decreasing the excitability of the neuron. PMID:21723921

  17. Activity dependence of action potential duration in rat supraoptic neurosecretory neurones recorded in vitro.

    PubMed

    Bourque, C W; Renaud, L P

    1985-06-01

    Action potential durations, measured at one-third peak amplitude, were examined during intracellular recordings in 134 supraoptic nucleus neurones maintained in vitro in perfused hypothalamic explants. Spike durations ranged between 1.2 and 3.9 ms and were dependent on firing frequency. Shortest measurements (1.74 +/- 0.03 ms; mean +/- S.E. of mean) were obtained during relative quiescence, i.e. less than or equal to 0.5 Hz. A gradual increase in firing frequency through continuous injection of depolarizing current prolonged spike duration, with maximum levels (2.68 +/- 0.05 ms) achieved at 20 Hz. When interspike interval variability was eliminated and firing was more precisely regulated by brief 15-20 ms intracellular current pulses given at pre-determined frequencies, a proportional relationship between increasing spike duration and firing frequency was retained but the change in spike duration at frequencies between 2 and 10 Hz was less pronounced. Once action potentials had achieved the long duration configuration, their return to the shorter duration took place gradually during any succeeding silent interval with a time constant of 4.9 s. Action potential broadening occurred progressively and was most pronounced at the onset of spontaneous or current-induced bursts. In thirty-six phasically active neurones, spike broadening at the onset of a burst was concurrent with the presence of 5-10 consecutive short (less than or equal to 100 ms) interspike intervals; thereafter, despite a greater than 50% reduction in firing frequency, action potential durations remained prolonged throughout the burst. In all of nineteen cells tested, frequency-dependent changes in spike duration were reversibly decreased or blocked by Cd2+, Co2+ and Mn2+, or when CaCl2 was exchanged for equimolar amounts of EGTA in the perfusion medium. These observations indicate that a Ca2+ conductance contributes to frequency- and firing-pattern-dependent changes in spike duration in rat supraoptic

  18. Contributions of HERG K+ current to repolarization of the human ventricular action potential.

    PubMed

    Fink, Martin; Noble, Denis; Virag, Laszlo; Varro, Andras; Giles, Wayne R

    2008-01-01

    Action potential repolarization in the mammalian heart is governed by interactions of a number of time- and voltage-dependent channel-mediated currents, as well as contributions from the Na+/Ca2+ exchanger and the Na+/K+ pump. Recent work has shown that one of the K+ currents (HERG) which contributes to repolarization in mammalian ventricle is a locus at which a number of point mutations can have significant functional consequences. In addition, the remarkable sensitivity of this K+ channel isoform to inhibition by a variety of pharmacological agents and clinical drugs has resulted in HERG being a major focus for Safety Pharmacology requirements. For these reasons we and others have attempted to define the functional role for HERG-mediated K+ currents in repolarization of the action potential in the human ventricle. Here, we describe and evaluate changes in the formulations for two K+ currents, IK1 and HERG (or IK,r), within the framework of ten Tusscher model of the human ventricular action potential. In this computational study, new mathematical formulations for the two nonlinear K+ conductances, IK1 and HERG, have been developed based upon experimental data obtained from electrophysiological studies of excised human ventricular tissue and/or myocytes. The resulting mathematical model provides much improved simulations of the relative sizes and time courses of the K+ currents which modulate repolarization. Our new formulation represents an important first step in defining the mechanism(s) of repolarization of the membrane action potential in the human ventricle. Our overall goal is to understand the genesis of the T-wave of the human electrocardiogram.

  19. Effects of ropinirole on action potential characteristics and the underlying ion currents in canine ventricular myocytes.

    PubMed

    Simkó, József; Szentandrássy, Norbert; Harmati, Gábor; Bárándi, László; Horváth, Balázs; Magyar, János; Bányász, Tamás; Lorincz, István; Nánási, Péter P

    2010-09-01

    In spite of its widespread clinical application, there is little information on the cellular cardiac effects of the dopamine receptor agonist ropinirole. In the present study, therefore, the concentration-dependent effects of ropinirole on action potential morphology and the underlying ion currents were studied in enzymatically dispersed canine ventricular cardiomyocytes using standard microelectrode, conventional whole-cell patch clamp, and action potential voltage clamp techniques. At concentrations > or = 1 microM, ropinirole increased action potential duration (APD(90)) and suppressed the rapid delayed rectifier K(+) current (I (Kr)) with an IC(50) value of 2.7 +/- 0.25 microM and Hill coefficient of 0.92 +/- 0.09. The block increased with increasing depolarizations to more positive voltages, but paradoxically, the activation of I (Kr) was accelerated by 3 muM ropinirole (time constant decreased from 34 +/- 4 to 14 +/- 1 ms). No significant changes in the fast and slow deactivation time constants were observed with ropinirole. At higher concentrations, ropinirole decreased the amplitude of early repolarization (at concentrations > or = 10 microM), reduced the maximum rate of depolarization and caused depression of the plateau (at concentrations > or = 30 microM), and shortened APD measured at 50% repolarization (at 300 microM) indicating a concentration-dependent inhibition of I (to), I (Na), and I (Ca). Suppression of I (Kr), I (to), and I (Ca) has been confirmed under conventional patch clamp and action potential voltage clamp conditions. I (Ks) and I (K1) were not influenced significantly by ropinirole at concentrations less than 300 microM. All these effects of ropinirole were fully reversible upon washout. The results indicate that ropinirole treatment may carry proarrhythmic risk for patients with inherited or acquired long QT syndrome due to inhibition of I (Kr)-especially in cases of accidental overdose or intoxication.

  20. Application of the optical method in experimental cardiology: action potential and intracellular calcium concentration measurement.

    PubMed

    Ronzhina, M; Cmiel, V; Janoušek, O; Kolářová, J; Nováková, M; Babula, P; Provazník, I

    2013-01-01

    It has been shown that, in addition to conventional contact electrode techniques, optical methods using fluorescent dyes can be successfully used for cardiac signal measurement. In this review, the physical and technical fundamentals of the method are described, as well as the properties of the most common systems for measuring action potentials and intracellular calcium concentration. Special attention is paid to summarizing limitations and trends in developing this method.

  1. ER Stress-Mediated Signaling: Action Potential and Ca2+ as Key Players

    PubMed Central

    Bahar, Entaz; Kim, Hyongsuk; Yoon, Hyonok

    2016-01-01

    The proper functioning of the endoplasmic reticulum (ER) is crucial for multiple cellular activities and survival. Disturbances in the normal ER functions lead to the accumulation and aggregation of unfolded proteins, which initiates an adaptive response, the unfolded protein response (UPR), in order to regain normal ER functions. Failure to activate the adaptive response initiates the process of programmed cell death or apoptosis. Apoptosis plays an important role in cell elimination, which is essential for embryogenesis, development, and tissue homeostasis. Impaired apoptosis can lead to the development of various pathological conditions, such as neurodegenerative and autoimmune diseases, cancer, or acquired immune deficiency syndrome (AIDS). Calcium (Ca2+) is one of the key regulators of cell survival and it can induce ER stress-mediated apoptosis in response to various conditions. Ca2+ regulates cell death both at the early and late stages of apoptosis. Severe Ca2+ dysregulation can promote cell death through apoptosis. Action potential, an electrical signal transmitted along the neurons and muscle fibers, is important for conveying information to, from, and within the brain. Upon the initiation of the action potential, increased levels of cytosolic Ca2+ (depolarization) lead to the activation of the ER stress response involved in the initiation of apoptosis. In this review, we discuss the involvement of Ca2+ and action potential in ER stress-mediated apoptosis. PMID:27649160

  2. Action potential characteristics of demyelinated rat sciatic nerve following application of 4-aminopyridine.

    PubMed

    Targ, E F; Kocsis, J D

    1986-01-15

    The sciatic nerves of rats were demyelinated by microinjection of lysophosphatidylcholine. A variety of abnormalities such as conduction slowing and block were present. Application of the potassium channel blocker 4-aminopyridine (4-AP) to the lesion site, led to an increase in area of the compound action potential recorded across the site of demyelination. Single axon recordings revealed three types of changes that may account for the 4-AP-induced increase in the compound response. One group showed broadening of the action potential. Other axons showed hyperexcitability following 4-AP, as manifest by spontaneous firing and multiple spike discharge following a single stimulus. In some of the axons studied, 4-AP led to overcoming of conduction block. Although many axons showed increased excitability properties in the presence of 4-AP, the frequency-following ability of the axons was reduced, and the absolute refractory period of the axons was increased. These results indicate that pharmacological blockade of potassium channels with 4-AP not only leads to action potential broadening in demyelinated axons, but to a variety of excitability changes. These heterogeneous effects of 4-AP should be considered in the rationale for its clinical use.

  3. 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.

  4. TASK-1 Channels May Modulate Action Potential Duration of Human Atrial Cardiomyocytes

    PubMed Central

    Limberg, Sven H.; Netter, Michael F.; Rolfes, Caroline; Rinné, Susanne; Schlichthörl, Günter; Zuzarte, Marylou; Vassiliou, Timon; Moosdorf, Rainer; Wulf, Hinnerk; Daut, Jürgen; Sachse, Frank B.; Decher, Niels

    2011-01-01

    Background/Aims: Atrial fibrillation is the most common arrhythmia in the elderly, and potassium channels with atrium-specific expression have been discussed as targets to treat atrial fibrillation. Our aim was to characterize TASK-1 channels in human heart and to functionally describe the role of the atrial whole cell current ITASK-1. Methods and Results: Using quantitative PCR, we show that TASK-1 is predominantly expressed in the atria, auricles and atrio-ventricular node of the human heart. Single channel recordings show the functional expression of TASK-1 in right human auricles. In addition, we describe for the first time the whole cell current carried by TASK-1 channels (ITASK-1) in human atrial tissue. We show that ITASK-1 contributes to the sustained outward current IKsus and that ITASK-1 is a major component of the background conductance in human atrial cardiomyocytes. Using patch clamp recordings and mathematical modeling of action potentials, we demonstrate that modulation of ITASK-1 can alter human atrial action potential duration. Conclusion: Due to the lack of ventricular expression and the ability to alter human atrial action potential duration, TASK-1 might be a drug target for the treatment of atrial fibrillation. PMID:22178873

  5. 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.

  6. The role of dendritic action potentials and Ca2+ influx in the induction of homosynaptic long-term depression in hippocampal CA1 pyramidal neurons.

    PubMed

    Christie, B R; Magee, J C; Johnston, D

    1996-01-01

    Long-term depression (LTD) of synaptic efficacy at CA1 synapses is believed to be a Ca(2+)-dependent process. We used high-speed fluorescence imaging and patch-clamp techniques to quantify the spatial distribution of changes in intracellular Ca2+ accompanying the induction of LTD at Schaffer collateral synapses in CA1 pyramidal neurons. Low-frequency stimulation (3 Hz), which was subthreshold for action potentials, produced small changes in [Ca2+]i and failed to elicit LTD. Increasing the stimulus strength so that action potentials were generated produced both robust LTD and increases in [Ca2+]i. Back-propagating action potentials at 3 Hz in the absence of synaptic stimulation also produced increases in [Ca2+]i, but failed to induce LTD. When subthreshold synaptic stimulation was paired with back-propagating action potentials, however, large increases in [Ca2+]i were observed and robust LTD was induced. The LTD was blocked by the N-methyl-D-aspartate receptor (NMDAr) antagonist APV, and stimulus-induced increases in [Ca2+]i were reduced throughout the neuron under these conditions. The LTD was also dependent on Ca2+ influx via voltage-gated Ca2+ channels (VGCCs), because LTD was severely attenuated or blocked by both nimodipine and Ni2+. These findings suggest that back-propagating action potentials can exert a powerful control over the induction of LTD and that both VGCCs and NMDArs are involved in the induction of this form of plasticity.

  7. T-type calcium channels consolidate tonic action potential output of thalamic neurons to neocortex.

    PubMed

    Deleuze, Charlotte; David, François; Béhuret, Sébastien; Sadoc, Gérard; Shin, Hee-Sup; Uebele, Victor N; Renger, John J; Lambert, Régis C; Leresche, Nathalie; Bal, Thierry

    2012-08-29

    The thalamic output during different behavioral states is strictly controlled by the firing modes of thalamocortical neurons. During sleep, their hyperpolarized membrane potential allows activation of the T-type calcium channels, promoting rhythmic high-frequency burst firing that reduces sensory information transfer. In contrast, in the waking state thalamic neurons mostly exhibit action potentials at low frequency (i.e., tonic firing), enabling the reliable transfer of incoming sensory inputs to cortex. Because of their nearly complete inactivation at the depolarized potentials that are experienced during the wake state, T-channels are not believed to modulate tonic action potential discharges. Here, we demonstrate using mice brain slices that activation of T-channels in thalamocortical neurons maintained in the depolarized/wake-like state is critical for the reliable expression of tonic firing, securing their excitability over changes in membrane potential that occur in the depolarized state. Our results establish a novel mechanism for the integration of sensory information by thalamocortical neurons and point to an unexpected role for T-channels in the early stage of information processing.

  8. Action-potential broadening and endogenously sustained bursting are substrates of command ability in a feeding neuron of Pleurobranchaea.

    PubMed

    Gillette, R; Gillette, M U; Davis, W J

    1980-03-01

    1. The ventral white cells (VWC's) of the buccal ganglion of Pleurobranchaea, so named for their position and color, are a bilateral pair of neuron somata. Each sends a single axon out its contralateral stomatogastric nerve and has a dendritic field originating close to the soma. 2. The vwcs exhibit spontaneous episodes of prolonged depolarization (duration 1--4 min) accompanied by repetitive action-potential activity and separated by regular intervals of 3--30 min. Such prolonged burst episodes can be triggered by short pulses of depolarizing current. During the repetitive activity of the spontaneous bursts or that driven by imposed depolarization, the action potentials progressively broaden to 5--16 times their initial duration. 3. During spontaneous bursting or activity driven by imposed depolarization, the cyclic motor output of the feeding network is initiated or accelerated with a latency corresponding with the development of appreciable VWC spike broadening. When broadening of antidromic VWC spikes is suppressed by imposed hyperpolarization of the soma, the frequency of feeding cycles is significantly lower than when broadened spikes are allowed to develop. When trains of spikes are driven by depolarizing current, the motor output of the feeding network is not initiated until the VWC spikes have broadened to a repeatable "threshold" duration, regardless of the intensity of the depolarizing current. 4. The endogenous production of prolonged burst episodes, triggered by depolarizing current pulses, and progressive spike broadening can be demonstrated in the surgically isolated VWC soma. 5. The paired VWCs are strongly electrically coupled and display highly synchronous activity. They receive synaptic inputs from many previously identified interneurons of the feeding network and are thus reciprocally coupled within the network. 6. These results demonstrate that the capacity of this neuron to generate broadened action potentials during repetitive activity

  9. Regulation of gap junction conductance by calcineurin through Cx43 phosphorylation: implications for action potential conduction.

    PubMed

    Jabr, Rita I; Hatch, Fiona S; Salvage, Samantha C; Orlowski, Alejandro; Lampe, Paul D; Fry, Christopher H

    2016-11-01

    Cardiac arrhythmias are associated with raised intracellular [Ca(2+)] and slowed action potential conduction caused by reduced gap junction (GJ) electrical conductance (Gj). Ventricular GJs are composed of connexin proteins (Cx43), with Gj determined by Cx43 phosphorylation status. Connexin phosphorylation is an interplay between protein kinases and phosphatases but the precise pathways are unknown. We aimed to identify key Ca(2+)-dependent phosphorylation sites on Cx43 that regulate cardiac gap junction conductance and action potential conduction velocity. We investigated the role of the Ca(2+)-dependent phosphatase, calcineurin. Intracellular [Ca(2+)] was raised in guinea-pig myocardium by a low-Na solution or increased stimulation. Conduction velocity and Gj were measured in multicellular strips. Phosphorylation of Cx43 serine residues (S365 and S368) and of the intermediary regulator I1 at threonine35 was measured by Western blot. Measurements were made in the presence and absence of inhibitors to calcineurin, I1 or protein phosphatase-1 and phosphatase-2.Raised [Ca(2)(+)]i decreased Gj, reduced Cx43 phosphorylation at S365 and increased it at S368; these changes were reversed by calcineurin inhibitors. Cx43-S368 phosphorylation was reversed by the protein kinase C inhibitor chelerythrine. Raised [Ca(2+)]i also decreased I1 phosphorylation, also prevented by calcineurin inhibitors, to increase activity of the Ca(2+)-independent phosphatase, PPI. The PP1 inhibitor, tautomycin, prevented Cx43-365 dephosphorylation, Cx43-S368 phosphorylation and Gj reduction in raised [Ca(2+)]i. PP2A had no role. Conduction velocity was reduced by raised [Ca(2+)]i and reversed by calcineurin inhibitors. Reduced action potential conduction and Gj in raised [Ca(2+)] are regulated by calcineurin-dependent Cx43-S365 phosphorylation, leading to Cx43-S368 dephosphorylation. The calcineurin action is indirect, via I1 dephosphorylation and subsequent activation of PP1.

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

    SciTech Connect

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

    2015-03-10

    We present a new method for constraining the Milky Way halo gravitational potential by simultaneously fitting multiple tidal streams. This method requires three-dimensional positions and velocities for all stars to be fit, but does not require identification of any specific stream or determination of stream membership for any star. We exploit the principle that the action distribution of stream stars is most clustered when the potential used to calculate the actions is closest to the true potential. Clustering is quantified with the Kullback-Leibler Divergence (KLD), which also provides conditional uncertainties for our parameter estimates. We show, for toy Gaia-like 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.

  11. Environmental Asthma Reduction Potential Estimates for Selected Mitigation Actions in Finland Using a Life Table Approach

    PubMed Central

    Rumrich, Isabell Katharina; Hänninen, Otto

    2015-01-01

    Aims: To quantify the reduction potential of asthma in Finland achievable by adjusting exposures to selected environmental factors. Methods: A life table model for the Finnish population for 1986–2040 was developed and Years Lived with Disability caused by asthma and attributable to the following selected exposures were estimated: tobacco smoke (smoking and second hand tobacco smoke), ambient fine particles, indoor dampness and mould, and pets. Results: At baseline (2011) about 25% of the total asthma burden was attributable to the selected exposures. Banning tobacco was the most efficient mitigation action, leading to 6% reduction of the asthma burden. A 50% reduction in exposure to dampness and mould as well as a doubling in exposure to pets lead each to a 2% reduction. Ban of urban small scale wood combustion, chosen as a mitigation action to reduce exposure to fine particles, leads to a reduction of less than 1% of the total asthma burden. Combination of the most efficient mitigation actions reduces the total asthma burden by 10%. A more feasible combination of mitigation actions leads to 6% reduction of the asthma burden. Conclusions: The adjustment of environmental exposures can reduce the asthma burden in Finland by up to 10%. PMID:26067987

  12. Analytic treatment of the compound action potential: Estimating the summed post-stimulus time histogram and unit response

    NASA Astrophysics Data System (ADS)

    Chertoff, Mark E.

    2004-11-01

    The convolution of an equation representing a summed post-stimulus time histogram computed across auditory nerve fibers [P(t)] with an equation representing a single-unit wave form [U(t)], resulted in an analytic expression for the compound action potential (CAP). The solution was fit to CAPs recorded to low and high frequency stimuli at various signal levels. The correlation between the CAP and the analytic expression was generally greater than 0.90. At high levels the width of P(t) was broader for low frequency stimuli than for high frequency signals, but delays were comparable. This indicates that at high signal levels there is an overlap in the population of auditory nerve fibers contributing to the CAP for both low and high frequency stimuli but low frequencies include contributions from more apical regions. At low signal levels the width of P(t) decreased for most frequencies and delays increased. The frequency of oscillation of U(t) was largest for high frequency stimuli and decreased for low frequency stimuli. The decay of U(t) was largest at 8 kHz and smallest at 1 kHz. These results indicate that the hair cell or neural mechanisms involved in the generation of action potentials may differ along the cochlear partition. .

  13. Synergistic action of nectins and cadherins generates the mosaic cellular pattern of the olfactory epithelium

    PubMed Central

    Katsunuma, Sayaka; Honda, Hisao; Shinoda, Tomoyasu; Ishimoto, Yukitaka; Miyata, Takaki; Kiyonari, Hiroshi; Abe, Takaya; Nibu, Ken-ichi; Takai, Yoshimi

    2016-01-01

    In the olfactory epithelium (OE), olfactory cells (OCs) and supporting cells (SCs), which express different cadherins, are arranged in a characteristic mosaic pattern in which OCs are enclosed by SCs. However, the mechanism underlying this cellular patterning is unclear. Here, we show that the cellular pattern of the OE is established by cellular rearrangements during development. In the OE, OCs express nectin-2 and N-cadherin, and SCs express nectin-2, nectin-3, E-cadherin, and N-cadherin. Heterophilic trans-interaction between nectin-2 on OCs and nectin-3 on SCs preferentially recruits cadherin via α-catenin to heterotypic junctions, and the differential distributions of cadherins between junctions promote cellular intercalations, resulting in the formation of the mosaic pattern. These observations are confirmed by model cell systems, and various cellular patterns are generated by the combinatorial expression of nectins and cadherins. Collectively, the synergistic action of nectins and cadherins generates mosaic pattern, which cannot be achieved by a single mechanism. PMID:26929452

  14. Potentiation of antimalarial drug action by chlorpheniramine against multidrug-resistant Plasmodium falciparum in vitro.

    PubMed

    Nakornchai, Sunan; Konthiang, Phattanapong

    2006-09-01

    Chlorpheniramine, a histamine H1 receptor antagonist, was assayed for in vitro antimalarial activity against multidrug-resistant Plasmodium falciparum K1 strain and chloroquine-resistant P. falciparum T9/94 clone, by measuring the 3H-hypoxanthine incorporation. Chlorphenirame inhibited P. falciparum K1 and T9/94 growth with IC50 values of 136.0+/-40.2 microM and 102.0+/-22.6 microM respectively. A combination of antimalarial drug and chlorpheniramine was tested against resistant P. falciparum in vitro. Isobologram analysis showed that chlorpheniramine exerts marked synergistic action on chloroquine against P. falciparum K1 and T9/94. Chlorpheniramine also potentiated antimalarial action of mefloquine, quinine or pyronaridine against both of the resistant strains of P. falciparum. However, chlorpheniramine antagonism with artesunate was obtained in both P. falciparum K1 and T9/94. The results in this study indicate that antihistaminic drugs may be promising candidates for potentiating antimalarial drug action against drug resistant malarial parasites.

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

    PubMed

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

    2011-01-01

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

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

    PubMed Central

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

    2010-01-01

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

  17. Sural sensory nerve action potential: A study in healthy Indian subjects

    PubMed Central

    Sreenivasan, Aarthika; Mansukhani, Khushnuma A; Sharma, Alika; Balakrishnan, Lajita

    2016-01-01

    Background: The sural sensory nerve action potential (SNAP) is an important electrodiagnostic study for suspected peripheral neuropathies. Incorrect technique and unavailability of reference data can lead to erroneous conclusions. Objectives: To establish reference data for sural SNAP in age-stratified healthy subjects at three sites of stimulation. Materials and Methods: A prospective study was conducted in 146 nerves from healthy subjects aged between 18 years and 90 years, stratified into six age groups (a = 18-30 years, b = 31–40 years, c = 41–50 years, d = 51–60 years, e = 61–70 years, and f >71 years). Sural SNAP was recorded antidromically, stimulating at three sites at distances of 14 cm, 12 cm, and 10 cm from the recording electrode. Mean – 2 standard deviation (SD) of the transformed data was used to generate reference values for amplitudes. Analysis of variance (ANOVA) test was used for inter-group and between three sites comparisons of amplitudes. Results: The lower limits of amplitude at 14 cm were 12.4 μV, 10.4 μV, 6.5 μV, 5.3 μV, 2.9 μV, and 1.9 μV; at 12 cm were 13.5 μV, 13.6 μV, 8.5 μV, 7.8 μV, 3.5 μV, and 2.8 μV; and at 10 cm were 16.3 μV, 16.3 μV, 11.1 μV, 10.0 μV, 4.8 μV, and 3.7 μV for groups a, b, c, d, e, and f, respectively. A statistically significant difference in amplitudes was noted from the three different sites of stimulation (P < 0.001). The amplitude differed significantly above the age of 60 years (P < 0.01) but not between groups e and f (P > 0.05). Conclusion: This study provides reference data for sural SNAP in Indian population at three different sites of stimulation along the calf in six age groups. It also shows significant variation in amplitude from the three different sites of stimulation. PMID:27570380

  18. A novel anionic conductance affects action potential duration in isolated rat ventricular myocytes.

    PubMed

    Spencer, C I; Uchida, W; Kozlowski, R Z

    2000-01-01

    Effects of extracellular anions were studied in electrophysiological experiments on freshly isolated rat ventricular myocytes. Under current-clamp, action potential duration (APD) was prolonged by reducing the extracellular Cl(-) concentration and shortened by replacement of extracellular Cl(-) with I(-). Under voltage-clamp, membrane potential steps or ramps evoked an anionic background current (I(AB)) carried by either Cl(-), Br(-), I(-) or NO(3)(-). Activation of I(AB) was Ca(2+)- and cyclic AMP-independent, and was unaffected by cell shrinkage. I(AB) was insensitive to stilbene and fenamate anion transport blockers at concentrations that inhibit Ca(2+)-, cyclic AMP- and swelling-activated Cl(-) currents in ventricular cells of other mammals. These results suggest that I(AB) may be carried by a novel class of Cl(-) channel. Correlation of anion substitution experiments on membrane current and action potentials revealed that I(AB) could play a major role in controlling rat ventricular APD. These findings have important implications for those studying cardiac Cl(-) channels as potential targets for novel antiarrythmic agents.

  19. Constraining the Galactic potential via action-based distribution functions for mono-abundance stellar populations

    NASA Astrophysics Data System (ADS)

    Ting, Yuan-Sen; Rix, Hans-Walter; Bovy, Jo; van de Ven, Glenn

    2013-09-01

    We present a rigorous and practical way of constraining the Galactic potential based on the phase-space information for many individual stars. Such an approach is needed to dynamically model the data from ongoing spectroscopic surveys of the Galaxy and in the future Gaia. This approach describes the orbit distribution of stars by a family of parametrized distribution function (DF) proposed by McMillan and Binney, which are based on actions. We find that these parametrized DFs are flexible enough to capture well the observed phase-space distributions of individual abundance-selected Galactic subpopulations of stars (`mono-abundance populations') for a disc-like gravitational potential, which enables independent dynamical constraints from each of the Galactic mono-abundance populations. We lay out a statistically rigorous way to constrain the Galactic potential parameters by constructing the joint likelihood of potential and DF parameters, and subsequently marginalizing over the DF parameters. This approach explicitly incorporates the spatial selection function inherent to all Galactic surveys, and can account for the uncertainties of the individual position-velocity observations. On that basis, we study the precision of the parameters of the Galactic potential that can be reached with various sample sizes and realistic spatial selection functions. By creating mock samples from the DF, we show that, even under a restrictive and realistic spatial selection function, given a two-parameter gravitational potential, one can recover the true potential parameters to a few per cent with sample sizes of a few thousands. The assumptions of axisymmetry, of DFs that are smooth in the actions and of no time variation remain important limitations in our current study.

  20. Effects of rosiglitazone on the configuration of action potentials and ion currents in canine ventricular cells

    PubMed Central

    Szentandrássy, N; Harmati, G; Bárándi, L; Simkó, J; Horváth, B; Magyar, J; Bányász, T; Lőrincz, I; Szebeni, A; Kecskeméti, V; Nánási, PP

    2011-01-01

    BACKGROUND AND PURPOSE In spite of its widespread clinical application, there is little information on the cellular cardiac effects of the antidiabetic drug rosiglitazone in larger experimental animals. In the present study therefore concentration-dependent effects of rosiglitazone on action potential morphology and the underlying ion currents were studied in dog hearts. EXPERIMENTAL APPROACH Standard microelectrode techniques, conventional whole cell patch clamp and action potential voltage clamp techniques were applied in enzymatically dispersed ventricular cells from dog hearts. KEY RESULTS At concentrations ≥10 µM rosiglitazone decreased the amplitude of phase-1 repolarization, reduced the maximum velocity of depolarization and caused depression of the plateau potential. These effects developed rapidly and were readily reversible upon washout. Rosiglitazone suppressed several transmembrane ion currents, concentration-dependently, under conventional voltage clamp conditions and altered their kinetic properties. The EC50 value for this inhibition was 25.2 ± 2.7 µM for the transient outward K+ current (Ito), 72.3 ± 9.3 µM for the rapid delayed rectifier K+ current (IKr) and 82.5 ± 9.4 µM for the L-type Ca2+ current (ICa) with Hill coefficients close to unity. The inward rectifier K+ current (IK1) was not affected by rosiglitazone up to concentrations of 100 µM. Suppression of Ito, IKr, and ICa was confirmed also under action potential voltage clamp conditions. CONCLUSIONS AND IMPLICATIONS Alterations in the densities and kinetic properties of ion currents may carry serious pro-arrhythmic risk in case of overdose with rosiglitazone, especially in patients having multiple cardiovascular risk factors, like elderly diabetic patients. LINKED ARTICLE This article is commented on by Hancox, pp. 496–498 of this issue. To view this commentary visit http://dx.doi.org/10.1111/j.1476-5381.2011.01281.x PMID:21232044

  1. FMRP regulates neurotransmitter release and synaptic information transmission by modulating action potential duration via BK channels.

    PubMed

    Deng, Pan-Yue; Rotman, Ziv; Blundon, Jay A; Cho, Yongcheol; Cui, Jianmin; Cavalli, Valeria; Zakharenko, Stanislav S; Klyachko, Vitaly A

    2013-02-20

    Loss of FMRP causes fragile X syndrome (FXS), but the physiological functions of FMRP remain highly debatable. Here we show that FMRP regulates neurotransmitter release in CA3 pyramidal neurons by modulating action potential (AP) duration. Loss of FMRP leads to excessive AP broadening during repetitive activity, enhanced presynaptic calcium influx, and elevated neurotransmitter release. The AP broadening defects caused by FMRP loss have a cell-autonomous presynaptic origin and can be acutely rescued in postnatal neurons. These presynaptic actions of FMRP are translation independent and are mediated selectively by BK channels via interaction of FMRP with BK channel's regulatory β4 subunits. Information-theoretical analysis demonstrates that loss of these FMRP functions causes marked dysregulation of synaptic information transmission. FMRP-dependent AP broadening is not limited to the hippocampus, but also occurs in cortical pyramidal neurons. Our results thus suggest major translation-independent presynaptic functions of FMRP that may have important implications for understanding FXS neuropathology.

  2. Regional differences in action potential characteristics and membrane currents of guinea-pig left ventricular myocytes.

    PubMed

    Main, M C; Bryant, S M; Hart, G

    1998-11-01

    Regional differences in action potential characteristics and membrane currents were investigated in subendocardial, midmyocardial and subepicardial myocytes isolated from the left ventricular free wall of guinea-pig hearts. Action potential duration (APD) was dependent on the region of origin of the myocytes (P < 0.01, ANOVA). Mean action potential duration at 90 % repolarization (APD90) was 237 +/- 8 ms in subendocardial (n = 30 myocytes), 251 +/- 7 ms in midmyocardial (n = 30) and 204 +/- 7 ms in subepicardial myocytes (n = 36). L-type calcium current (ICa) density and background potassium current (IK1) density were similar in the three regions studied. Delayed rectifier current (IK) was measured as deactivating tail current, elicited on repolarization back to -45 mV after 2 s step depolarizations to test potentials ranging from -10 to +80 mV. Mean IK density (after a step to +80 mV) was larger in subepicardial myocytes (1.59 +/- 0.16 pA pF-1, n = 16) than in either subendocardial (1.16 +/- 0.12 pA pF-1, n = 17) or midmyocardial (1. 13 +/- 0.11 pA pF-1, n = 21) myocytes (P < 0.05, ANOVA). The La3+-insensitive current (IKs) elicited on repolarization back to -45 mV after a 250 ms step depolarization to +60 mV was similar in the three regions studied. The La3+-sensitive tail current, (IKr) was greater in subepicardial (0.50 +/- 0.04 pA pF-1, n = 11) than in subendocardial (0.25 +/- 0.05 pA pF-1, n = 9) or in midmyocardial myocytes (0.38 +/- 0.05 pA pF-1, n = 11, P < 0.05, ANOVA). The contribution of a Na+ background current to regional differences in APD was assessed by application of 0.1 microM tetrodotoxin (TTX). TTX-induced shortening of APD90 was greater in subendocardial myocytes (35.7 +/- 7.1 %, n = 11) than in midmyocardial (15.7 +/- 3. 8 %, n = 10) and subepicardial (20.2 +/- 4.3 %, n = 11) myocytes (P < 0.05, ANOVA). Regional differences in action potential characteristics between subendocardial, midmyocardial, and subepicardial myocytes isolated from

  3. Born in the USA: how immigrant generation shapes meritocracy and its relation to ethnic identity and collective action.

    PubMed

    Wiley, Shaun; Deaux, Kay; Hagelskamp, Carolin

    2012-04-01

    Endorsing meritocracy can make low-status group members more accepting of inequality. This study examined whether rejecting meritocracy is related to increased ethnic identification among Latino immigrants, and whether identity in turn is related to increased support for collective action. We hypothesize that these relationships depend upon immigrant generation. A survey was conducted with 184 first- and second-generation Latino immigrants in New York City. Second-generation Latinos endorsed meritocracy less than those in the first generation, at least in part because they perceived that other Americans viewed their group in a less positive light (i.e., lower public regard). Further, meritocracy was negatively linked to ethnic identity and, through it, support for collective action among the second generation. Among the first generation, meritocracy was not related to ethnic identity and was positively related to support for collective action. We discuss the implications of growing up near the bottom of the U.S. social hierarchy for ethnic identity and collective action.

  4. 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

  5. Stretch-induced excitation and action potential changes of single cardiac cells.

    PubMed

    Riemer, Tara L; Tung, Leslie

    2003-01-01

    Mechanoelectric coupling (MEC) has been studied extensively in the heart at the tissue and organ levels, but to only a limited extent in single cells because of the technical challenges. New results are presented in which MEC was studied in 57 single frog ventricular myocytes that were held on both ends by glass holding pipettes. Axial stretch was applied either by displacement of the pipettes, or by a glass fiber around which the cell was wrapped, that was displaced in a pulsatile or sinusoidal fashion. Electrical activity of the cell was monitored either by active contraction, by intracellular action potentials, or by focal extracellular potentials. Of more than 350 stretches applied to 57 cells with amplitudes ranging from 3% to 35%, only 4 cases of mechanically induced stimulation were observed. In 252 stretches applied to 32 cells in which action potential duration (APD) was measured, no change >20% was observed, except in 3 cells in which APD increased by >100%, and in 2 cells with extended triggered activity. Thus, in contrast to studies in intact tissue, single frog ventricular myocytes are generally insensitive to direct axial stretch. However, robust mechanosensitive responses were observed in 7 of 57 ( approximately 12%) cells. The results of other single cell studies are reviewed, and the significance of differences in tissue-level and single cell results is discussed.

  6. 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

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

    PubMed

    Pearman, Charles M

    2014-12-01

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

  8. 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

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

    PubMed Central

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

    2015-01-01

    Based on lysotracker red imaging in cultured hippocampal neurons, antipsychotic drugs (APDs) were proposed to accumulate in synaptic vesicles by acidic trapping and to be released in response to action potentials. Because many APDs are dopamine (DA) D2 receptor (D2R) antagonists, such a mechanism would be particularly interesting if it operated in midbrain DA neurons. Here, the APD cyamemazine (CYAM) is visualized directly by two-photon microscopy in substantia nigra and striatum brain slices. CYAM accumulated slowly into puncta based on vacuolar H+-ATPase activity and dispersed rapidly upon dissipating organelle pH gradients. Thus, CYAM is subject to acidic trapping and released upon deprotonation. In the striatum, Ca2+-dependent reduction of the CYAM punctate signal was induced by depolarization or action potentials. Striatal CYAM overlapped with the dopamine transporter (DAT). Furthermore, parachloroamphetamine (pCA), acting via vesicular monoamine transporter (VMAT), and a charged VMAT, substrate 1-methyl-4-phenylpyridinium (MPP+), reduced striatal CYAM. In vivo CYAM administration and in vitro experiments confirmed that clinically relevant CYAM concentrations result in vesicular accumulation and pCA-dependent release. These results show that some CYAM is in DA neuron VMAT vesicles and suggests a new drug interaction in which amphetamine induces CYAM deprotonation and release as a consequence of the H+ countertransport by VMAT that accompanies vesicular uptake, but not by inducing exchange or acting as a weak base. Therefore, in the striatum, APDs are released with DA in response to action potentials and an amphetamine. This synaptic corelease is expected to enhance APD antagonism of D2Rs where and when dopaminergic transmission occurs. PMID:26216995

  10. Neuronal Competition for Action Potential Initiation Sites in a Circuit Controlling Simple Learning

    PubMed Central

    Cruz, Georgina E.; Sahley, Christie L.; Muller, Kenneth J.

    2007-01-01

    The spatial and temporal patterns of action potential initiations were studied in a behaving leech preparation to determine the basis of increased firing that accompanies sensitization, a form of non-associative learning requiring the S-interneurons. Little is known at the network level about mechanisms of behavioral sensitization. The S-interneurons, one in each ganglion and linked by electrical synapses with both neighbors to form a chain, are interposed between sensory and motor neurons. In sensitized preparations the strength of shortening is related to S-cell firing, which itself is the result of impulses initiating in several S-cells. Because the S-cells, as independent initiation sites, all contribute to activity in the chain, it was hypothesized that during sensitization, increased multi-site activity increased the chain's firing rate. However, it was found that during sensitization, the single site with the largest initiation rate, the S-cell in the stimulated segment, suppressed initiations in adjacent ganglia. Experiments showed this was both because (1) it received the earliest, greatest input and (2) the delayed synaptic input to the adjacent S-cells coincided with the action potential refractory period. A compartmental model of the S-cell and its inputs showed that a simple, intrinsic mechanism of inexcitability after each action potential may account for suppression of impulse initiations. Thus, a non-synaptic competition between neurons alters synaptic integration in the chain. In one mode, inputs to different sites sum independently, whereas in another, synaptic input to a single site precisely specifies the overall pattern of activity. PMID:17644266

  11. Evaluation of global onshore wind energy potential and generation costs.

    PubMed

    Zhou, Yuyu; Luckow, Patrick; Smith, Steven J; Clarke, Leon

    2012-07-17

    In this study, we develop an updated global estimate of onshore wind energy potential using reanalysis wind speed data, along with updated wind turbine technology performance, land suitability factors, cost assumptions, and explicit consideration of transmission distance in the calculation of transmission costs. We find that wind has the potential to supply a significant portion of the world energy needs, although this potential varies substantially by region and with assumptions such as on what types of land can be used to site wind farms. Total global economic wind potential under central assumptions, that is, intermediate between optimistic and pessimistic, is estimated to be approximately 119.5 petawatt hours per year (13.6 TW) at less than 9 cents/kWh. A sensitivity analysis of eight key parameters is presented. Wind potential is sensitive to a number of input parameters, particularly wind speed (varying by -70% to +450% at less than 9 cents/kWh), land suitability (by -55% to +25%), turbine density (by -60% to +80%), and cost and financing options (by -20% to +200%), many of which have important policy implications. As a result of sensitivities studied here we suggest that further research intended to inform wind supply curve development focus not purely on physical science, such as better resolved wind maps, but also on these less well-defined factors, such as land-suitability, that will also have an impact on the long-term role of wind power.

  12. Nonthermal Argon Plasma Generator and Some Potential Applications

    NASA Astrophysics Data System (ADS)

    Bunoiu, M.; Jugunaru, I.; Bica, I.; Balasoiu, M.

    2015-12-01

    A laboratory - made nonthermal plasma generator is presented. It has a diameter of 0.020 m and length of 0.155 m and contains two electrodes. The first electrode is a 2% Th-W alloy, 0.002 m in diameter bar, centred inside the generator's body by means of a four channel teflon piece; the other three channels, 0.003 m in diameter, are used for Ar supply. The second electrode is a nozzle of 0.002 m - 0.008 m diameter and 0.005m length. A ~500 kV/m electric field is generated between the two electrodes by a high frequency source (13.56 MHz ±5%), equipped with a OT-1000 (Tungsram) power triode. For Ar flows ranging from 0.00008 m3/s to 0.00056 m3/s, a plasma jet of length not exceeding 0.015 m and temperature below 315 K is obtained. Anthurium andraeanumis sample , blood matrix, human hair and textile fibers may be introduced in the plasma jet. For time periods of 30 s and 60 s, various effects like, cell detexturization, fast blood coagulation or textile fiber or hair cleaning and smoothing are obtained. These effects are presented and discussed in the paper.

  13. Ionic remodeling underlying action potential changes in a canine model of atrial fibrillation.

    PubMed

    Yue, L; Feng, J; Gaspo, R; Li, G R; Wang, Z; Nattel, S

    1997-10-01

    Rapid electrical activation, as occurs during atrial fibrillation (AF), is known to cause reductions in atrial refractoriness and in adaptation to heart rate of the atrial refractory period, which promote the maintenance of AF, but the underlying ionic mechanisms are unknown. In order to determine the cellular and ionic changes caused by chronic atrial tachycardia, we studied right atrial myocytes from dogs subjected to 1, 7, or 42 days of atrial pacing at 400/min and compared them with myocytes from sham-operated dogs (pacemaker inserted but not activated). Rapid pacing led to progressive increases in the duration of AF induced by bursts of 10-Hz stimuli (from 3 +/- 2 seconds in sham-operated dogs to 3060 +/- 707 seconds in dogs after 42 days of pacing, P < .001) and reduced atrial refractoriness and adaptation to rate of the atrial refractory period. Voltage-clamp studies showed that chronic rapid pacing did not alter inward rectifier K+ current, rapid or slow components of the delayed rectifier current, the ultrarapid delayed rectifier current, T-type Ca2+ current, or Ca(2+)-dependent Cl- current. In contrast, the densities of transient outward current (Ito) and L-type Ca2+ current (ICa) were progressively reduced as the duration of rapid pacing increased, without concomitant changes in kinetics or voltage dependence. In keeping with in vivo changes in refractoriness, action potential duration (APD) and APD adaptation to rate were decreased by rapid pacing. The response of the action potential and ionic currents flowing during the action potential (as exposed by action-potential voltage clamp) to nifedipine in normal canine cells and in cells from rapidly paced dogs suggested that the APD changes in paced dogs were largely due to reductions in ICa. We conclude that sustained atrial tachycardia reduces Ito and ICa, that the reduced ICa decreases APD and APD adaptation to rate, and that these cellular changes likely account for the alterations in atrial

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

    PubMed

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

    2014-01-15

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

  15. The Healthy Bus project in Denmark: need for an action potential assessment.

    PubMed

    Poulsen, Kjeld B

    2004-06-01

    Research over the last 50 years has repeatedly documented that bus drivers are exposed to several physical and psychological risk factors, which are associated with health problems in the form of heart, musculo-skeletal and stomach disease, and increased coronary mortality. So why has there been little action to improve the situation when it is so obviously indicated by such assessments? This article describes the long and complex process that has made it possible to launch almost 200 interventions among the 3500 municipal bus drivers in Copenhagen. Using a participative action research design, new evidence was gathered by broadening the traditional work environmental scope to lifestyle, health issues and private matters. Comparing this updated needs assessment with a national reference population, it was found that drivers were often still worse off. Again, simply presenting new evidence did not seem to lead to changes and further work is needed to empower the stakeholders so that they can commit to start making effective interventions. It is concluded that every needs assessment has to be supplemented with an evaluation of the action potential.

  16. Ketamine and the next generation of antidepressants with a rapid onset of action

    PubMed Central

    Machado-Vieira, Rodrigo; Salvadore, Giacomo; DiazGranados, Nancy; Zarate, Carlos A

    2009-01-01

    Existing treatments for major depressive disorder (MDD) usually take weeks to months to achieve their antidepressant effects, and a significant number of patients do not have adequate improvement even after months of treatment. In addition, increased risk of suicide attempts is a major public health concern during the first month of standard antidepressant therapy. Thus, improved therapeutics that can exert their antidepressant effects within hours or a few days of their administration are urgently needed, as is a better understanding of the presumed mechanisms associated with these rapid antidepressant effects. In this context, the N-methyl-D-aspartate (NMDA) antagonist ketamine has consistently shown antidepressant effects within a few hours of its administration. This makes it a valuable research tool to identify biomarkers of response in order to develop the next generation of fast-acting antidepressants. In this review, we describe clinical, electrophysiological, biochemical, and imaging correlates as relevant targets in the study of the antidepressant response associated with ketamine, and their implications for the development of novel, fast-acting antidepressants. We also review evidence that alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) to NMDA throughput may represent a convergent mechanism for the rapid antidepressant actions of ketamine. Overall, understanding the molecular basis of this work will likely lead to the ultimate development of improved therapeutics for MDD. PMID:19397926

  17. Assessment of Distributed Generation Potential in JapaneseBuildings

    SciTech Connect

    Zhou, Nan; Marnay, Chris; Firestone, Ryan; Gao, Weijun; Nishida,Masaru

    2005-05-25

    To meet growing energy demands, energy efficiency, renewable energy, and on-site generation coupled with effective utilization of exhaust heat will all be required. Additional benefit can be achieved by integrating these distributed technologies into distributed energy resource (DER) systems (or microgrids). This research investigates a method of choosing economically optimal DER, expanding on prior studies at the Berkeley Lab using the DER design optimization program, the Distributed Energy Resources Customer Adoption Model (DER-CAM). DER-CAM finds the optimal combination of installed equipment from available DER technologies, given prevailing utility tariffs, site electrical and thermal loads, and a menu of available equipment. It provides a global optimization, albeit idealized, that shows how the site energy loads can be served at minimum cost by selection and operation of on-site generation, heat recovery, and cooling. Five prototype Japanese commercial buildings are examined and DER-CAM applied to select the economically optimal DER system for each. The five building types are office, hospital, hotel, retail, and sports facility. Based on the optimization results, energy and emission reductions are evaluated. Furthermore, a Japan-U.S. comparison study of policy, technology, and utility tariffs relevant to DER installation is presented. Significant decreases in fuel consumption, carbon emissions, and energy costs were seen in the DER-CAM results. Savings were most noticeable in the sports facility (a very favourable CHP site), followed by the hospital, hotel, and office building.

  18. Three-dimensional mapping and regulation of action potential propagation in nanoelectronics innervated tissues

    PubMed Central

    Dai, Xiaochuan; Zhou, Wei; Gao, Teng; Liu, Jia; Lieber, Charles M.

    2016-01-01

    Real-time mapping and manipulation of electrophysiology in three-dimensional (3D) tissues could impact broadly fundamental scientific and clinical studies, yet realization lacks effective methods. Here we introduce tissue-scaffold-mimicking 3D nanoelectronic arrays consisting of 64 addressable devices with subcellular dimensions and sub-millisecond time-resolution. Real-time extracellular action potential (AP) recordings reveal quantitative maps of AP propagation in 3D cardiac tissues, enable in situ tracing of the evolving topology of 3D conducting pathways in developing cardiac tissues, and probe the dynamics of AP conduction characteristics in a transient arrhythmia disease model and subsequent tissue self-adaptation. We further demonstrate simultaneous multi-site stimulation and mapping to manipulate actively the frequency and direction of AP propagation. These results establish new methodologies for 3D spatiotemporal tissue recording and control, and demonstrate the potential to impact regenerative medicine, pharmacology and electronic therapeutics. PMID:27347837

  19. Single action potentials and subthreshold electrical events imaged in neurons with a fluorescent protein voltage probe.

    PubMed

    Jin, Lei; Han, Zhou; Platisa, Jelena; Wooltorton, Julian R A; Cohen, Lawrence B; Pieribone, Vincent A

    2012-09-06

    Monitoring neuronal electrical activity using fluorescent protein-based voltage sensors has been limited by small response magnitudes and slow kinetics of existing probes. Here we report the development of a fluorescent protein voltage sensor, named ArcLight, and derivative probes that exhibit large changes in fluorescence intensity in response to voltage changes. ArcLight consists of the voltage-sensing domain of Ciona intestinalis voltage-sensitive phosphatase and super ecliptic pHluorin that carries the point mutation A227D. The fluorescence intensity of ArcLight A242 decreases by 35% in response to a 100 mV depolarization when measured in HEK293 cells, which is more than five times larger than the signals from previously reported fluorescent protein voltage sensors. We show that the combination of signal size and response speed of these new probes allows the reliable detection of single action potentials and excitatory potentials in individual neurons and dendrites.

  20. Three-dimensional mapping and regulation of action potential propagation in nanoelectronics-innervated tissues

    NASA Astrophysics Data System (ADS)

    Dai, Xiaochuan; Zhou, Wei; Gao, Teng; Liu, Jia; Lieber, Charles M.

    2016-09-01

    Real-time mapping and manipulation of electrophysiology in three-dimensional (3D) tissues could have important impacts on fundamental scientific and clinical studies, yet realization is hampered by a lack of effective methods. Here we introduce tissue-scaffold-mimicking 3D nanoelectronic arrays consisting of 64 addressable devices with subcellular dimensions and a submillisecond temporal resolution. Real-time extracellular action potential (AP) recordings reveal quantitative maps of AP propagation in 3D cardiac tissues, enable in situ tracing of the evolving topology of 3D conducting pathways in developing cardiac tissues and probe the dynamics of AP conduction characteristics in a transient arrhythmia disease model and subsequent tissue self-adaptation. We further demonstrate simultaneous multisite stimulation and mapping to actively manipulate the frequency and direction of AP propagation. These results establish new methodologies for 3D spatiotemporal tissue recording and control, and demonstrate the potential to impact regenerative medicine, pharmacology and electronic therapeutics.

  1. Three-dimensional mapping and regulation of action potential propagation in nanoelectronics-innervated tissues.

    PubMed

    Dai, Xiaochuan; Zhou, Wei; Gao, Teng; Liu, Jia; Lieber, Charles M

    2016-09-01

    Real-time mapping and manipulation of electrophysiology in three-dimensional (3D) tissues could have important impacts on fundamental scientific and clinical studies, yet realization is hampered by a lack of effective methods. Here we introduce tissue-scaffold-mimicking 3D nanoelectronic arrays consisting of 64 addressable devices with subcellular dimensions and a submillisecond temporal resolution. Real-time extracellular action potential (AP) recordings reveal quantitative maps of AP propagation in 3D cardiac tissues, enable in situ tracing of the evolving topology of 3D conducting pathways in developing cardiac tissues and probe the dynamics of AP conduction characteristics in a transient arrhythmia disease model and subsequent tissue self-adaptation. We further demonstrate simultaneous multisite stimulation and mapping to actively manipulate the frequency and direction of AP propagation. These results establish new methodologies for 3D spatiotemporal tissue recording and control, and demonstrate the potential to impact regenerative medicine, pharmacology and electronic therapeutics.

  2. 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

    2016-08-11

    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.

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

    NASA Astrophysics Data System (ADS)

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

    2016-08-01

    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.

  4. Epac activator critically regulates action potential duration by decreasing potassium current in rat adult ventricle.

    PubMed

    Brette, Fabien; Blandin, Erick; Simard, Christophe; Guinamard, Romain; Sallé, Laurent

    2013-04-01

    Sympathetic stimulation is an important modulator of cardiac function via the classic cAMP-dependent signaling pathway, PKA. Recently, this paradigm has been challenged by the discovery of a family of guanine nucleotide exchange proteins directly activated by cAMP (Epac), acting in parallel to the classic signaling pathway. In cardiac myocytes, Epac activation is known to modulate Ca(2+) cycling yet their actions on cardiac ionic currents remain poorly characterized. This study attempts to address this paucity of information using the patch clamp technique to record action potential (AP) and ionic currents on rat ventricular myocytes. Epac was selectively activated by 8-CPT-AM (acetoxymethyl ester form of 8-CPT). AP amplitude, maximum depolarization rate and resting membrane amplitude were unaltered by 8-CPT-AM, strongly suggesting that Na(+) current and inward rectifier K(+) current are not regulated by Epac. In contrast, AP duration was significantly increased by 8-CPT-AM (prolongation of duration at 50% and 90% of repolarization by 41±10% and 43±8% respectively, n=11). L-type Ca(2+) current density was unaltered by 8-CPT-AM (n=16) so this cannot explain the action potential lengthening. However, the steady state component of K(+) current was significantly inhibited by 8-CPT-AM (-38±6%, n=15), while the transient outward K(+) current was unaffected by 8-CPT-AM. These effects were PKA-independent since they were observed in the presence of PKA inhibitor KT5720. Isoprenaline (100nM) induced a significant prolongation of AP duration, even in the presence of KT5720. This study provides the first evidence that the cAMP-binding protein Epac critically modulates cardiac AP duration by decreasing steady state K(+) current. These observations may be relevant to diseases in which Epac is upregulated, like cardiac hypertrophy.

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

    PubMed Central

    Abouelela, Ahmed; Wieraszko, Andrzej

    2016-01-01

    Background Our previous experiments demonstrated modulation of the amplitude of the axonal compound action potential (CAP) by electrical stimulation. To verify assumption that glutamate released from axons could be involved in this phenomenon, the modification of the axonal CAP induced by glutamate was investigated. Objectives The major objective of this research is to verify the hypothesis that axonal activity would trigger the release of glutamate, which in turn would interact with specific axonal receptors modifying the amplitude of the action potential. Methods Segments of the sciatic nerve were exposed to exogenous glutamate in vitro, and CAP was recorded before and after glutamate application. In some experiments, the release of radioactive glutamate analog from the sciatic nerve exposed to exogenous glutamate was also evaluated. Results The glutamate-induced increase in CAP was blocked by different glutamate receptor antagonists. The effect of glutamate was not observed in Ca-free medium, and was blocked by antagonists of calcium channels. Exogenous glutamate, applied to the segments of sciatic nerve, induced the release of radioactive glutamate analog, demonstrating glutamate-induced glutamate release. Immunohistochemical examination revealed that axolemma contains components necessary for glutamatergic neurotransmission. Conclusion The proteins of the axonal membrane can under the influence of electrical stimulation or exogenous glutamate change membrane permeability and ionic conductance, leading to a change in the amplitude of CAP. We suggest that increased axonal activity leads to the release of glutamate that results in changes in the amplitude of CAPs. PMID:28077958

  6. Targeting intracellular p-aminobenzoic acid production potentiates the anti-tubercular action of antifolates

    PubMed Central

    Thiede, Joshua M.; Kordus, Shannon L.; Turman, Breanna J.; Buonomo, Joseph A.; Aldrich, Courtney C.; Minato, Yusuke; Baughn, Anthony D.

    2016-01-01

    The ability to revitalize and re-purpose existing drugs offers a powerful approach for novel treatment options against Mycobacterium tuberculosis and other infectious agents. Antifolates are an underutilized drug class in tuberculosis (TB) therapy, capable of disrupting the biosynthesis of tetrahydrofolate, an essential cellular cofactor. Based on the observation that exogenously supplied p-aminobenzoic acid (PABA) can antagonize the action of antifolates that interact with dihydropteroate synthase (DHPS), such as sulfonamides and p-aminosalicylic acid (PAS), we hypothesized that bacterial PABA biosynthesis contributes to intrinsic antifolate resistance. Herein, we demonstrate that disruption of PABA biosynthesis potentiates the anti-tubercular action of DHPS inhibitors and PAS by up to 1000 fold. Disruption of PABA biosynthesis is also demonstrated to lead to loss of viability over time. Further, we demonstrate that this strategy restores the wild type level of PAS susceptibility in a previously characterized PAS resistant strain of M. tuberculosis. Finally, we demonstrate selective inhibition of PABA biosynthesis in M. tuberculosis using the small molecule MAC173979. This study reveals that the M. tuberculosis PABA biosynthetic pathway is responsible for intrinsic resistance to various antifolates and this pathway is a chemically vulnerable target whose disruption could potentiate the tuberculocidal activity of an underutilized class of antimicrobial agents. PMID:27905500

  7. 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

  8. 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

  9. Action-potential-independent GABAergic tone mediated by nicotinic stimulation of immature striatal miniature synaptic transmission.

    PubMed

    Liu, Zhi; Otsu, Yo; Vasuta, Cristina; Nawa, Hiroyuki; Murphy, Timothy H

    2007-08-01

    Stimulation of presynaptic nicotinic acetylcholine receptors (nAChRs) increases the frequency of miniature excitatory synaptic activity (mEPSCs) to a point where they can promote cell firing in hippocampal CA3 neurons. We have evaluated whether nicotine regulation of miniature synaptic activity can be extended to inhibitory transmission onto striatal medium spiny projection neurons (MSNs) in acute brain slices. Bath application of micromolar nicotine typically induced 12-fold increases in the frequency of miniature inhibitory synaptic currents (mIPSCs). Little effect was observed on the amplitude of mIPSCs or mEPSCs under these conditions. Nicotine stimulation of mIPSCs was dependent on entry of extracellular calcium because removal of calcium from perfusate was able to block its action. To assess the potential physiological significance of the nicotine-stimulated increase in mIPSC frequency, we also examined the nicotine effect on evoked IPSCs (eIPSCs). eIPSCs were markedly attenuated by nicotine. This effect could be attributed to two potential mechanisms: transmitter depletion due to extremely high mIPSC rates and/or a reduction in presynaptic excitability associated with nicotinic depolarization. Treatment with low concentrations of K(+) was able to in part mimic nicotine's stimulatory effect on mIPSCs and inhibitory effect on eIPSCs. Current-clamp recordings confirmed a direct depolarizing action of nicotine that could dampen eIPSC activity leading to a switch to striatal inhibitory synaptic transmission mediated by tonic mIPSCs.

  10. Amphetamine augments action potential-dependent dopaminergic signaling in the striatum in vivo.

    PubMed

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

    2011-06-01

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

  11. Applications of control theory to the dynamics and propagation of cardiac action potentials.

    PubMed

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

    2010-09-01

    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.

  12. 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

  13. 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

  14. Frequency-dependent inhibition of antidromic hippocampal compound action potentials by anti-convulsants.

    PubMed

    Teriakidis, Adrianna; Brown, Jon T; Randall, Andrew

    2006-01-01

    Using rat hippocampal slices, extracellularly recorded antidromic compound action potentials (cAP) were produced in CA1 pyramidal cell populations by electrical stimulation of the alveus at 0.5 Hz. These responses were additionally examined across a range of stimulus frequencies between 0.5 and 100 Hz. Anticonvulsant drugs in clinical use were applied via perfusion of the recording chamber. Three anticonvulsants produced a concentration-dependent inhibition of the cAP evoked at low frequency (0.5 Hz). The following IC(50) values were observed: lamotrigine, 210 microM (interpolated); carbamazepine, 210 microM (interpolated); phenytoin, 400 microM (extrapolated). The extent of inhibition produced was increased when trains of 30 cAPs were evoked at frequencies > or 30 Hz. This frequency dependence was quantified by measuring a response integral for a range of compound concentrations. Three other compounds valproate (5 mM), topiramate (500 microM) and levetiracetam (500 microM) produced no clear effect at any stimulus frequency tested. Using this simple neurophysiological assay it has been possible to compare the use-dependent inhibition of hippocampal action potentials by a range of anticonvulsants, providing a useful adjunct to patch clamp studies of such molecules at Na(+) channels. There is no clear correlation between the activity in this model and the clinical efficacy of these drugs in different forms of epilepsy.

  15. The use of sensory action potential to evaluate inferior alveolar nerve damage after orthognathic surgery.

    PubMed

    Calabria, Francesca; Sellek, Lucy; Gugole, Fabio; Trevisiol, Lorenzo; Trevisol, Lorenzo; Bertolasi, Laura; D'Agostino, Antonio

    2013-03-01

    To assess and monitor the common event of neurosensory disturbance to the inferior alveolar nerve (IAN) after bilateral sagittal split osteotomy, we used clinical sensory tests and neurophysiologic test sensory action potentials. The diagnostic value of these tests was evaluated by comparing them with the degree of nerve damage reported by patients. Fourteen patients undergoing bilateral sagittal split osteotomy were analyzed preoperatively and 2 years postoperatively. Patients were evaluated bilaterally for positive and negative symptoms: light touch sensation, paraesthesia, hyperesthesia, and dysaesthesia; a "sensation score" was then calculated for each patient. Patients were also asked if they would be willing to repeat the procedure knowing the sensation loss they had now. Next, the right and left IAN were evaluated using sensory action potential and correlated with the other results. Before surgery, the medium latency difference between left and right was lower compared with postsurgery, with all patients having some deficit. The reduction in medium amplitude of 67% after the intervention was statistically significant. The frequency of abnormal findings in the electrophysiologic tests indicating IAN injury correlated with subjective sensory alteration. All patients said that they would repeat the surgery. Electrophysiologic testing is recommended for the evaluation of nerve dysfunction and seems a sensitive method for accurately assessing postsurgical nerve conduction.

  16. Effects of acoustic noise on the auditory nerve compound action potentials evoked by electric pulse trains.

    PubMed

    Nourski, Kirill V; Abbas, Paul J; Miller, Charles A; Robinson, Barbara K; Jeng, Fuh-Cherng

    2005-04-01

    This study investigated the effects of acoustic noise on the auditory nerve compound action potentials in response to electric pulse trains. Subjects were adult guinea pigs, implanted with a minimally invasive electrode to preserve acoustic sensitivity. Electrically evoked compound action potentials (ECAP) were recorded from the auditory nerve trunk in response to electric pulse trains both during and after the presentation of acoustic white noise. Simultaneously presented acoustic noise produced a decrease in ECAP amplitude. The effect of the acoustic masker on the electric probe was greatest at the onset of the acoustic stimulus and it was followed by a partial recovery of the ECAP amplitude. Following cessation of the acoustic noise, ECAP amplitude recovered over a period of approximately 100-200 ms. The effects of the acoustic noise were more prominent at lower electric pulse rates (interpulse intervals of 3 ms and higher). At higher pulse rates, the ECAP adaptation to the electric pulse train alone was larger and the acoustic noise, when presented, produced little additional effect. The observed effects of noise on ECAP were the greatest at high electric stimulus levels and, for a particular electric stimulus level, at high acoustic noise levels.

  17. Modulation of action potential and calcium signaling by levetiracetam in rat sensory neurons.

    PubMed

    Ozcan, Mete; Ayar, Ahmet

    2012-06-01

    Levetiracetam (LEV), a new anticonvulsant agent primarily used to treat epilepsy, has been used in pain treatment but the cellular mechanism of this action remains unclear. This study aimed to investigate effects of LEV on the excitability and membrane depolarization-induced calcium signaling in isolated rat sensory neurons using the whole-cell patch clamp and fura 2-based ratiometric Ca(2+)-imaging techniques. Dorsal root ganglia (DRG) were excised from neonatal rats, and cultured following enzymatic and mechanical dissociation. Under current clamp conditions, acute application of LEV (30 µM, 100 µM and 300 µM) significantly increased input resistance and caused the membrane to hyperpolarize from resting membrane potential in a dose-dependent manner. Reversal potentials of action potential (AP) after hyperpolarising amplitudes were shifted to more negative, toward to potassium equilibrium potentials, after application of LEV. It also caused a decrease in number of APs in neurons fired multiple APs in response to prolonged depolarization. Fura-2 fluorescence Ca(2+) imaging protocols revealed that HiK(+) (30 mM)-induced intracellular free Ca(2+) ([Ca(2+)](i)) was inhibited to 97.8 ± 4.6% (n = 17), 92.6 ± 4.8% (n = 17, p < 0.01) and 89.1 ± 5.1% (n = 18, p < 0.01) after application of 30 µM, 100 µM and 300 µM LEV (respectively), without any significant effect on basal levels of [Ca(2+)](i). This is the first evidence for the effect of LEV on the excitability of rat sensory neurons through an effect which might involve activation of potassium channels and inhibition of entry of Ca(2+), providing new insights for cellular mechanism(s) of LEV in pain treatment modalities.

  18. Whey protein potentiates the intestinotrophic action of glucagon-like peptide-2 in parenterally fed rats.

    PubMed

    Liu, Xiaowen; Murali, Sangita G; Holst, Jens J; Ney, Denise M

    2009-11-01

    Glucagon-like peptide-2 (GLP-2) is a nutrient-regulated intestinotrophic hormone derived from proglucagon in the distal intestine. Enteral nutrients (EN) potentiate the action of GLP-2 to reverse parenteral nutrition (PN)-induced mucosal hypoplasia. The objective was to determine what enteral protein component, casein, soy, or whey protein, potentiates the intestinal growth response to GLP-2 in rats with PN-induced mucosal hypoplasia. Rats received PN and continuous intravenous infusion of GLP-2 (100 microg/kg/day) for 7 days. Six EN groups received PN+GLP-2 for days 1-3 and partial PN+GLP-2 plus EN for days 4-7. EN was provided by ad libitum intake of a semielemental liquid diet with different protein sources: casein, hydrolyzed soy, whey protein concentrate (WPC), and hydrolyzed WPC+casein. Controls received PN+GLP-2 alone. EN induced significantly greater jejunal sucrase activity and gain of body weight, and improved feed efficiency compared with PN+GLP-2 alone. EN induced greater ileal proglucagon expression, increased plasma concentration of bioactive GLP-2 by 35%, and reduced plasma dipeptidyl peptidase IV (DPP-IV) activity compared with PN+GLP-2 alone, P < 0.05. However, only whey protein, and not casein or soy, potentiated the ability of GLP-2 to reverse PN-induced mucosal hypoplasia and further increase ileal villus height, crypt depth, and mucosa cellularity compared with PN+GLP-2 alone, P < 0.05. The ability of whey protein to induce greater mucosal surface area was associated with decreased DPP-IV activity in ileum and colon compared with casein, soy, or PN+GLP-2 alone, P < 0.05. In conclusion, whey protein potentiates the action of GLP-2 to reverse PN-induced mucosal hypoplasia in association with decreased intestinal DPP-IV activity.

  19. Whey protein potentiates the intestinotrophic action of glucagon-like peptide-2 in parenterally fed rats

    PubMed Central

    Liu, Xiaowen; Murali, Sangita G.; Holst, Jens J.

    2009-01-01

    Glucagon-like peptide-2 (GLP-2) is a nutrient-regulated intestinotrophic hormone derived from proglucagon in the distal intestine. Enteral nutrients (EN) potentiate the action of GLP-2 to reverse parenteral nutrition (PN)-induced mucosal hypoplasia. The objective was to determine what enteral protein component, casein, soy, or whey protein, potentiates the intestinal growth response to GLP-2 in rats with PN-induced mucosal hypoplasia. Rats received PN and continuous intravenous infusion of GLP-2 (100 μg/kg/day) for 7 days. Six EN groups received PN+GLP-2 for days 1–3 and partial PN+GLP-2 plus EN for days 4–7. EN was provided by ad libitum intake of a semielemental liquid diet with different protein sources: casein, hydrolyzed soy, whey protein concentrate (WPC), and hydrolyzed WPC+casein. Controls received PN+GLP-2 alone. EN induced significantly greater jejunal sucrase activity and gain of body weight, and improved feed efficiency compared with PN+GLP-2 alone. EN induced greater ileal proglucagon expression, increased plasma concentration of bioactive GLP-2 by 35%, and reduced plasma dipeptidyl peptidase IV (DPP-IV) activity compared with PN+GLP-2 alone, P < 0.05. However, only whey protein, and not casein or soy, potentiated the ability of GLP-2 to reverse PN-induced mucosal hypoplasia and further increase ileal villus height, crypt depth, and mucosa cellularity compared with PN+GLP-2 alone, P < 0.05. The ability of whey protein to induce greater mucosal surface area was associated with decreased DPP-IV activity in ileum and colon compared with casein, soy, or PN+GLP-2 alone, P < 0.05. In conclusion, whey protein potentiates the action of GLP-2 to reverse PN-induced mucosal hypoplasia in association with decreased intestinal DPP-IV activity. PMID:19776251

  20. Infinitesimal generators and quasi-units in potential theory

    PubMed Central

    Arsove, Maynard; Leutwiler, Heinz

    1975-01-01

    The underlying structure is taken as a strongly superharmonic cone [unk], defined as a partially ordered abelian semigroup with identity 0 which admits a multiplication by nonnegative scalars and satisfies two fundamental axioms of a potentialtheoretic character. In terms of a fixed nonzero element e there is introduced on [unk] a one-parameter family of nonlinear operators Sλ (λ ≥ 0) closely connected with the abstract theory of quasibounded and singular elements. The semigroup {Sλ} admits an infinitesimal generator A, and the elements invariant under A, called quasi-units, generalize the Yosida quasi-units in the theory of Riesz spaces. Quasi-units in [unk] are studied, both from a potentialtheoretic and a function-alanalytic viewpoint, culminating in a spectral representation theorem for quasi-bounded elements which extends the classical Freudenthal spectral theorem of Riesz space theory. PMID:16592260

  1. Back-propagating action potentials in pyramidal neurons: a putative signaling mechanism for the induction of Hebbian synaptic plasticity.

    PubMed

    Colbert, C M

    2001-01-01

    A hallmark of synaptic plasticity is the associative, or Hebbian, nature of its induction. By associative, we mean that the timing relationships between activity of the pre- and postsynaptic elements of a synapse determine whether synaptic strengths are modified. lt is well-established that associativity results, in large part, from the dual requirements for activation of the N-methyl-D-aspartate receptor-ionophore, namely presynaptic neurotransmitter release and postsynaptic depolarization. However, the specific dendritic events that provide the postsynaptic depolarization have been relatively unexplored. Increasing evidence suggests that back-propagating (i.e., antidromic) Na(+) action potentials provide the necessary postsynaptic depolarization to allow induction of associative synaptic plasticities. In hippocampal CAI and neocortical layer V pyramidal neurons, these action potentials provide much greater levels of dendritic depolarization than would be expected from synaptic currents alone. Moreover, they provide a relatively brief and synchronous depolarization throughout the dendritic arbor, allowing timing relationships to more directly reflect pre- and postsynaptic cell firing. Interestingly, certain properties of the back-propagating actions potentials differ from axonal or somatic action potentials in ways that seem to reflect their function. For example, the all-or-none property of action potential amplitude does not hold in the dendrites. In this review we discuss the back-propagating action potential as a dendritic signal that provides information to synapses about the firing state of the postsynaptic neuron. First, we consider the evidence that action potentials propagate back from the axon. Second, we describe the characteristics of the back-propagating action potential in terms of interactions of its underlying ionic currents. Third, we describe how these properties contribute to the timing aspects of the induction of long-term potentiation. Finally

  2. Potential improvements in SiGe radioisotope thermoelectric generator performance

    SciTech Connect

    Mowery, A.L.

    1999-01-01

    In accordance with NASA{close_quote}s slogan: {open_quotes}Better, Cheaper, Faster,{close_quotes} this paper will address potential improvements to SiGe RTG technology to make them Better. RTGs are doubtless cheaper than {open_quotes}paper designs{close_quotes} which are better and cheaper until development, performance and safety test costs are considered. RTGs have the advantage of being fully developed and tested in the rigors of space for over twenty years. Further, unless a new system can be accelerated tested, as were the RTGs, they cannot be deployed reliably unless a number of systems have succeeded for test periods exceeding the mission lifetime. Two potential developments are discussed that can improve the basic RTG performance by 10 to 40{sup +}{percent} depending on the mission profile. These improvements could be demonstrated in years. Accelerated testing could also be performed in this period to preserve existing RTG reliability. Data from a qualification tested RTG will be displayed, while not definitive, to support the conclusions. Finally, it is anticipated that other investigators will be encouraged to suggest further modifications to the basic RTG design to improve its performance. {copyright} {ital 1999 American Institute of Physics.}

  3. Action Potentials and Ion Conductances in Wild-type and CALHM1-knockout Type II Taste Cells.

    PubMed

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

    2017-02-15

    Taste bud type II cells fire action potentials in response to tastants, triggering non-vesicular ATP release to gustatory neurons via voltage-gated CALHM1-associated ion channels. Whereas CALHM1 regulates mouse cortical neuron excitability, its roles in regulating type II cell excitability are unknown. Here, we compared membrane conductances and action potentials in single identified TRPM5-GFP-expressing circumvallate papillae type II cells acutely isolated from wild-type (WT) and Calhm1-knockout (KO) mice. The activation kinetics of large voltage-gated outward currents were accelerated in cells from Calhm1-KO mice, and their associated non-selective tail currents, previously shown to be highly correlated with ATP release, were completely absent in Calhm1-KO cells, suggesting that CALHM1 contributes to all of these currents. Calhm1 deletion did not significantly alter resting membrane potential or input resistance, the amplitudes and kinetics of Na(+) currents either estimated from action potentials or recorded from steady-state voltage-pulses, or action potential threshold, overshoot peak, after-hyperpolarization and firing frequency. However, Calhm1-deletion reduced the half-widths of action potentials and accelerated the deactivation kinetics of transient outward currents, suggesting that the CALHM1-associated conductance becomes activated during the repolarization phase of action potentials.

  4. Resistance to action potential depression of a rat axon terminal in vivo.

    PubMed

    Sierksma, Martijn C; Borst, J Gerard G

    2017-04-03

    The shape of the presynaptic action potential (AP) has a strong impact on neurotransmitter release. Because of the small size of most terminals in the central nervous system, little is known about the regulation of their AP shape during natural firing patterns in vivo. The calyx of Held is a giant axosomatic terminal in the auditory brainstem, whose biophysical properties have been well studied in slices. Here, we made whole-cell recordings from calyceal terminals in newborn rat pups. The calyx showed a characteristic burst firing pattern, which has previously been shown to originate from the cochlea. Surprisingly, even for frequencies over 200 Hz, the AP showed little or no depression. Current injections showed that the rate of rise of the AP depended strongly on its onset potential, and that the membrane potential after the AP (Vafter) was close to the value at which no depression would occur during high-frequency activity. Immunolabeling revealed that Nav1.6 is already present at the calyx shortly after its formation, which was in line with the fast recovery from AP depression that we observed in slice recordings. Our findings thus indicate that fast recovery from depression and an inter-AP membrane potential that minimizes changes on the next AP in vivo, together enable high timing precision of the calyx of Held already shortly after its formation.

  5. 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.

  6. Calcium-dependent but action potential-independent BCM-like metaplasticity in the hippocampus.

    PubMed

    Hulme, Sarah R; Jones, Owen D; Ireland, David R; Abraham, Wickliffe C

    2012-05-16

    The Bienenstock, Cooper and Munro (BCM) computational model, which incorporates a metaplastic sliding threshold for LTP induction, accounts well for experience-dependent changes in synaptic plasticity in the visual cortex. BCM-like metaplasticity over a shorter timescale has also been observed in the hippocampus, thus providing a tractable experimental preparation for testing specific predictions of the model. Here, using extracellular and intracellular electrophysiological recordings from acute rat hippocampal slices, we tested the critical BCM predictions (1) that high levels of synaptic activation will induce a metaplastic state that spreads across dendritic compartments, and (2) that postsynaptic cell-firing is the critical trigger for inducing that state. In support of the first premise, high-frequency priming stimulation inhibited subsequent long-term potentiation and facilitated subsequent long-term depression at synapses quiescent during priming, including those located in a dendritic compartment different to that of the primed pathway. These effects were not dependent on changes in synaptic inhibition or NMDA/metabotropic glutamate receptor function. However, in contrast to the BCM prediction, somatic action potentials during priming were neither necessary nor sufficient to induce the metaplasticity effect. Instead, in broad agreement with derivatives of the BCM model, calcium as released from intracellular stores and triggered by M1 muscarinic acetylcholine receptor activation was critical for altering subsequent synaptic plasticity. These results indicate that synaptic plasticity in stratum radiatum of CA1 can be homeostatically regulated by the cell-wide history of synaptic activity through a calcium-dependent but action potential-independent mechanism.

  7. Action potential initiation in the peripheral terminals of cold-sensitive neurones innervating the guinea-pig cornea.

    PubMed

    Carr, Richard W; Pianova, Svetlana; McKemy, David D; Brock, James A

    2009-03-15

    The site at which action potentials initiate within the terminal region of unmyelinated sensory axons has not been resolved. Combining recordings of nerve terminal impulses (NTIs) and collision analysis, the site of action potential initiation in guinea-pig corneal cold receptors was determined. For most receptors (77%), initiation mapped to a point in the time domain that was closer to the nerve terminal than to the site of electrical stimulation at the back of the eye. Guinea-pig corneal cold receptors are Adelta-neurones that lose their myelin sheath at the point where they enter the cornea, and therefore their axons conduct more slowly within the cornea. Allowing for this inhomogeneity in conduction speed, the resulting spatial estimates of action potential initiation sites correlated with changes in NTI shape predicted by simulation of action potentials initiating within a nerve terminal. In some receptors, more than one NTI shape was observed. Simulations of NTI shape suggest that the origin of differing NTI shapes result from action potentials initiating at different, spatially discrete, locations within the nerve terminal. Importantly, the relative incidence of NTI shapes resulting from action potential initiation close to the nerve termination increased during warming when nerve activity decreased, indicating that the favoured site of action potential initiation shifts toward the nerve terminal when it hyperpolarizes. This finding can be explained by a hyperpolarization-induced relief of Na(+) channel inactivation in the nerve terminal. The results provide direct evidence that the molecular entities responsible for stimulus transduction and action potential initiation reside in parallel with one another in the unmyelinated nerve terminals of cold receptors.

  8. From evidence to action to deliver a healthy start for the next generation.

    PubMed

    Mason, Elizabeth; McDougall, Lori; Lawn, Joy E; Gupta, Anuradha; Claeson, Mariam; Pillay, Yogan; Presern, Carole; Lukong, Martina Baye; Mann, Gillian; Wijnroks, Marijke; Azad, Kishwar; Taylor, Katherine; Beattie, Allison; Bhutta, Zulfiqar A; Chopra, Mickey

    2014-08-02

    Remarkable progress has been made towards halving of maternal deaths and deaths of children aged 1-59 months, although the task is incomplete. Newborn deaths and stillbirths were largely invisible in the Millennium Development Goals, and have continued to fall between maternal and child health efforts, with much slower reduction. This Series and the Every Newborn Action Plan outline mortality goals for newborn babies (ten or fewer per 1000 livebirths) and stillbirths (ten or fewer per 1000 total births) by 2035, aligning with A Promise Renewed target for children and the vision of Every Woman Every Child. To focus political attention and improve performance, goals for newborn babies and stillbirths must be recognised in the post-2015 framework, with corresponding accountability mechanisms. The four previous papers in this Every Newborn Series show the potential for a triple return on investment around the time of birth: averting maternal and newborn deaths and preventing stillbirths. Beyond survival, being counted and optimum nutrition and development is a human right for all children, including those with disabilities. Improved human capital brings economic productivity. Efforts to reach every woman and every newborn baby, close gaps in coverage, and improve equity and quality for antenatal, intrapartum, and postnatal care, especially in the poorest countries and for underserved populations, need urgent attention. We have prioritised what needs to be done differently on the basis of learning from the past decade about what has worked, and what has not. Needed now are four most important shifts: (1) intensification of political attention and leadership; (2) promotion of parent voice, supporting women, families, and communities to speak up for their newborn babies and to challenge social norms that accept these deaths as inevitable; (3) investment for effect on mortality outcome as well as harmonisation of funding; (4) implementation at scale, with particular

  9. Neural mechanisms underlying immediate and final action goals in object use reflected by slow wave brain potentials.

    PubMed

    van Schie, Hein T; Bekkering, Harold

    2007-05-07

    Event-related brain potentials were used to study the neural mechanisms underlying goal-directed object use distinguishing between processes supporting immediate and final action goals during action planning and execution. Subjects performed a grasping and transportation task in which actions were cued either with the immediate action goal (the part of the object to grasp) or with the final action goal of the movement (the end position for transportation). Slow wave potentials dissociated between processes supporting immediate and final goals: reaching for the object was accompanied by the development of a parietal-occipital slow wave that peaked in congruency with the grasping event, whereas transport of the object towards the final goal location was found accompanied by slow wave components developing over left frontal regions with a peak towards the movement end. Source localization of cueing differences indicated activation centered around the parieto-occipital sulcus during reaching of the immediate action goal, followed by enhanced activation in the anterior prefrontal cortex during transport to the final action goal. These results suggest the existence of separate neural controllers for immediate and final action goals during the execution of goal-directed actions with objects.

  10. Green tea catechins potentiate the neuritogenic action of brain-derived neurotrophic factor: role of 67-kDa laminin receptor and hydrogen peroxide.

    PubMed

    Gundimeda, Usha; McNeill, Thomas H; Fan, Tiffany K; Deng, Ronald; Rayudu, David; Chen, Zachary; Cadenas, Enrique; Gopalakrishna, Rayudu

    2014-02-28

    Delivery of optimal amounts of brain-derived neurotrophic factor (BDNF) to regions of the brain affected by neurodegenerative diseases is a daunting task. Using natural products with neuroprotective properties, such as green tea polyphenols, would be a highly useful complementary approach for inexpensive long-term treatment of these diseases. In this study, we used PC12(TrkB) cells which ectopically express TrkB, a high affinity receptor for BDNF. They differentiate and induce neurite outgrowth in response to BDNF. Using this model, we show for the first time that treatment with extremely low concentrations (<0.1 μg/ml) of unfractionated green tea polyphenols (GTPP) and low concentrations (<0.5 μM) of their active ingredient, epigallocatechin-3-gallate (EGCG), potentiated the neuritogenic ability of a low concentration (2 ng/ml) of BDNF. A synergistic interaction was observed between GTPP constituents, where epigallocatechin and epicatechin, both individually lacking this activity, promoted the action of EGCG. GTPP-induced potentiation of BDNF action required the cell-surface associated 67 kDa laminin receptor (67LR) to which EGCG binds with high affinity. A cell-permeable catalase abolished GTPP/EGCG-induced potentiation of BDNF action, suggesting the possible involvement of H2O2 in the potentiation. Consistently, exogenous sublethal concentrations of H2O2, added as a bolus dose (5 μM) or more effectively through a steady-state generation (1 μM), potentiated BDNF action. Collectively, these results suggest that EGCG, dependent on 67 LR and H2O2, potentiates the neuritogenic action of BDNF. Intriguingly, this effect requires only submicromolar concentrations of EGCG. This is significant as extremely low concentrations of polyphenols are believed to reach the brain after drinking green tea.

  11. Modulation by K+ channels of action potential-evoked intracellular Ca2+ concentration rises in rat cerebellar basket cell axons

    PubMed Central

    Tan, Y P; Llano, I

    1999-01-01

    Action potential-evoked [Ca2+]i rises in basket cell axons of rat cerebellar slices were studied using two-photon laser scanning microscopy and whole-cell recording, to identify the K+ channels controlling the shape of the axonal action potential. Whole-cell recordings of Purkinje cell IPSCs were used to screen K+ channel subtypes which could contribute to axonal repolarization. α-Dendrotoxin, 4-aminopyridine, charybdotoxin and tetraethylammonium chloride increased IPSC rate and/or amplitude, whereas iberiotoxin and apamin failed to affect the IPSCs. The effects of those K+ channel blockers that enhanced transmitter release on the [Ca2+]i rises elicited in basket cell axons by action potentials fell into three groups: 4-aminopyridine strongly increased action potential-evoked [Ca2+]i; tetraethylammonium and charybdotoxin were ineffective alone but augmented the effects of 4-aminopyridine; α-dendrotoxin had no effect. We conclude that cerebellar basket cells contain at least three pharmacologically distinct K+ channels, which regulate transmitter release through different mechanisms. 4-Aminopyridine-sensitive, α-dendrotoxin-insensitive K+ channels are mainly responsible for repolarization in basket cell presynaptic terminals. K+ channels blocked by charybdotoxin and tetraethylammonium have a minor role in repolarization. α-Dendrotoxin-sensitive channels are not involved in shaping the axonal action potential waveform. The two last types of channels must therefore exert control of synaptic activity through a pathway unrelated to axonal action potential broadening. PMID:10517801

  12. Modulation by K+ channels of action potential-evoked intracellular Ca2+ concentration rises in rat cerebellar basket cell axons.

    PubMed

    Tan, Y P; Llano, I

    1999-10-01

    1. Action potential-evoked [Ca2+]i rises in basket cell axons of rat cerebellar slices were studied using two-photon laser scanning microscopy and whole-cell recording, to identify the K+ channels controlling the shape of the axonal action potential. 2. Whole-cell recordings of Purkinje cell IPSCs were used to screen K+ channel subtypes which could contribute to axonal repolarization. alpha-Dendrotoxin, 4-aminopyridine, charybdotoxin and tetraethylammonium chloride increased IPSC rate and/or amplitude, whereas iberiotoxin and apamin failed to affect the IPSCs. 3. The effects of those K+ channel blockers that enhanced transmitter release on the [Ca2+]i rises elicited in basket cell axons by action potentials fell into three groups: 4-aminopyridine strongly increased action potential-evoked [Ca2+]i; tetraethylammonium and charybdotoxin were ineffective alone but augmented the effects of 4-aminopyridine; alpha-dendrotoxin had no effect. 4. We conclude that cerebellar basket cells contain at least three pharmacologically distinct K+ channels, which regulate transmitter release through different mechanisms. 4-Aminopyridine-sensitive, alpha-dendrotoxin-insensitive K+ channels are mainly responsible for repolarization in basket cell presynaptic terminals. K+ channels blocked by charybdotoxin and tetraethylammonium have a minor role in repolarization. alpha-Dendrotoxin-sensitive channels are not involved in shaping the axonal action potential waveform. The two last types of channels must therefore exert control of synaptic activity through a pathway unrelated to axonal action potential broadening.

  13. The potential impact of washing machines on laundry malodour generation.

    PubMed

    Stapleton, K; Hill, K; Day, K; Perry, J D; Dean, J R

    2013-04-01

    A multidisciplinary approach has been adopted to investigate and identify the source of malodour in washing machines and the potential for cross-contamination of laundry. Four washing machines were olfactively graded, and the number of colony-forming units (CFUs) bacteria was determined in four specific locations. Then, samples of terry-towel and fleece were washed, without the use of detergent, in the machines, and the occurrence of malodour over a 52-h period was assessed. Analysis of the scrapings from the four locations in the two malodorous machines identified a plethora of volatile organic compounds (VOCs) by either olfactory detection or mass spectral identification post-gas chromatographic separation. In addition, microbiological analysis from the swabs from the four locations within all four washing machines was carried out. Quantitative analysis of VOCs from 66 microbiological isolates from either the washing machines or fabrics was carried out. In total, 10 VOCs were identified: dimethyl disulfide, 3-methyl-1-butanol, 2,4-dithiapentane, dimethyl trisulfide, 2-tridecanone, indole, 2-phenylethanol, isovaleric acid, isobutyric acid and 1-undecene.

  14. Spine Calcium Transients Induced by Synaptically-Evoked Action Potentials Can Predict Synapse Location and Establish Synaptic Democracy

    PubMed Central

    Meredith, Rhiannon M.; van Ooyen, Arjen

    2012-01-01

    CA1 pyramidal neurons receive hundreds of synaptic inputs at different distances from the soma. Distance-dependent synaptic scaling enables distal and proximal synapses to influence the somatic membrane equally, a phenomenon called “synaptic democracy”. How this is established is unclear. The backpropagating action potential (BAP) is hypothesised to provide distance-dependent information to synapses, allowing synaptic strengths to scale accordingly. Experimental measurements show that a BAP evoked by current injection at the soma causes calcium currents in the apical shaft whose amplitudes decay with distance from the soma. However, in vivo action potentials are not induced by somatic current injection but by synaptic inputs along the dendrites, which creates a different excitable state of the dendrites. Due to technical limitations, it is not possible to study experimentally whether distance information can also be provided by synaptically-evoked BAPs. Therefore we adapted a realistic morphological and electrophysiological model to measure BAP-induced voltage and calcium signals in spines after Schaffer collateral synapse stimulation. We show that peak calcium concentration is highly correlated with soma-synapse distance under a number of physiologically-realistic suprathreshold stimulation regimes and for a range of dendritic morphologies. Peak calcium levels also predicted the attenuation of the EPSP across the dendritic tree. Furthermore, we show that peak calcium can be used to set up a synaptic democracy in a homeostatic manner, whereby synapses regulate their synaptic strength on the basis of the difference between peak calcium and a uniform target value. We conclude that information derived from synaptically-generated BAPs can indicate synapse location and can subsequently be utilised to implement a synaptic democracy. PMID:22719238

  15. 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

  16. 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

  17. FMRP Regulates Neurotransmitter Release and Synaptic Information Transmission by Modulating Action Potential Duration via BK channels

    PubMed Central

    Deng, Pan-Yue; Rotman, Ziv; Blundon, Jay A.; Cho, Yongcheol; Cui, Jianmin; Cavalli, Valeria; Zakharenko, Stanislav S.; Klyachko, Vitaly A.

    2013-01-01

    SUMMARY Loss of FMRP causes Fragile X syndrome (FXS), but the physiological functions of FMRP remain highly debatable. Here we show that FMRP regulates neurotransmitter release in CA3 pyramidal neurons by modulating action potential (AP) duration. Loss of FMRP leads to excessive AP broadening during repetitive activity, enhanced presynaptic calcium influx and elevated neurotransmitter release. The AP broadening defects caused by FMRP loss have a cell-autonomous presynaptic origin and can be acutely rescued in postnatal neurons. These presynaptic actions of FMRP are translation-independent and are mediated selectively by BK channels via interaction of FMRP with BK channel’s regulatory β4 subunits. Information-theoretical analysis demonstrates that loss of these FMRP functions causes marked dysregulation of synaptic information transmission. FMRP-dependent AP broadening is not limited to the hippocampus, but also occurs in cortical pyramidal neurons. Our results thus suggest major translation-independent presynaptic functions of FMRP that may have important implications for understanding FXS neuropathology. PMID:23439122

  18. Diabatic heating fields and the generation of available potential energy during FGGE

    NASA Technical Reports Server (NTRS)

    Salstein, David A.; Rosen, Richard D.; Baker, Wayman E.; Kalnay, Eugenia

    1986-01-01

    Global diabatic heating is estimated using fields of directly computed heating components, in particular those due to shortwave radiation, longwave radiation, sensible heating, and latent heating produced every 6 hours. The role of average fields of diabatic heating in the generation of available potential energy is examined. It is observed that latent heating is most significant in generating available potential energy.

  19. 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

    2015-09-25

    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.

  20. 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.

  1. miR-19b Regulates Ventricular Action Potential Duration in Zebrafish

    PubMed Central

    Benz, Alexander; Kossack, Mandy; Auth, Dominik; Seyler, Claudia; Zitron, Edgar; Juergensen, Lonny; Katus, Hugo A.; Hassel, David

    2016-01-01

    Sudden cardiac death due to ventricular arrhythmias often caused by action potential duration (APD) prolongation is a common mode of death in heart failure (HF). microRNAs, noncoding RNAs that fine tune gene expression, are frequently dysregulated during HF, suggesting a potential involvement in the electrical remodeling process accompanying HF progression. Here, we identified miR-19b as an important regulator of heart function. Zebrafish lacking miR-19b developed severe bradycardia and reduced cardiac contractility. miR-19b deficient fish displayed increased sensitivity to AV-block, a characteristic feature of long QT syndrome in zebrafish. Patch clamp experiments from whole hearts showed that miR-19b deficient zebrafish exhibit significantly prolonged ventricular APD caused by impaired repolarization. We found that miR-19b directly and indirectly regulates the expression of crucial modulatory subunits of cardiac ion channels, and thereby modulates AP duration and shape. Interestingly, miR-19b knockdown mediated APD prolongation can rescue a genetically induced short QT phenotype. Thus, miR-19b might represent a crucial modifier of the cardiac electrical activity, and our work establishes miR-19b as a potential candidate for human long QT syndrome. PMID:27805004

  2. 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

  3. Control and Plasticity of the Presynaptic Action Potential Waveform at Small CNS Nerve Terminals

    PubMed Central

    Hoppa, Michael B.; Gouzer, Geraldine; Armbruster, Moritz; Ryan, Timothy A.

    2014-01-01

    SUMMARY The steep dependence of exocytosis on Ca2+ entry at nerve terminals implies that voltage control of both Ca2+ channel opening and the driving force for Ca2+ entry are powerful levers in sculpting synaptic efficacy. Using fast, genetically encoded voltage indicators in dissociated primary neurons, we show that at small nerve terminals K+ channels constrain the peak voltage of the presynaptic action potential (APSYN) to values much lower than those at cell somas. This key APSYN property additionally shows adaptive plasticity: manipulations that increase presynaptic Ca2+ channel abundance and release probability result in a commensurate lowering of the APSYN peak and narrowing of the waveform, while manipulations that decrease presynaptic Ca2+ channel abundance do the opposite. This modulation is eliminated upon blockade of Kv3.1 and Kv1 channels. Our studies thus reveal that adaptive plasticity in the APSYN waveform serves as an important regulator of synaptic function. PMID:25447742

  4. Action potential evoked transmitter release in central synapses: insights from the developing calyx of Held

    PubMed Central

    2009-01-01

    Chemical synapses are the fundamental units that mediate communication between neurons in the mammalian brain. In contrast to the enormous progress made in mapping out postsynaptic contributions of receptors, scaffolding structures and receptor trafficking to synaptic transmission and plasticity, the small size of nerve terminals has largely precluded direct analyses of presynaptic modulation of excitability and transmitter release in central synapses. Recent studies performed in accessible synapses such as the calyx of Held, a giant axosomatic synapse in the sound localization circuit of the auditory brainstem, have provided tremendous insights into how central synapses regulate the dynamic gain range of synaptic transmission. This review will highlight experimental evidence that resolves several long-standing issues with respect to intricate interplays between the waveform of action potentials, Ca2+ currents and transmitter release and further conceptualize their relationships in a physiological context with theoretical models of the spatial organization of voltage-gated Ca2+ channels and synaptic vesicles at release sites. PMID:19939269

  5. A Shab potassium channel contributes to action potential broadening in peptidergic neurons.

    PubMed

    Quattrocki, E A; Marshall, J; Kaczmarek, L K

    1994-01-01

    We have cloned the gene for a potassium channel, Aplysia Shab, that is expressed in the bag cell neurons of Aplysia. The voltage dependence and kinetics of the Aplysia Shab current in oocytes match those of IK2, one of the two delayed rectifiers in these neurons. Like IK2, but in contrast with other members of the Shab subfamily, the Aplysia Shab current inactivates within several hundred milliseconds. This inactivation occurs by a process whose properties do not match those previously described for C-type and N-type mechanisms. Neither truncation of the N-terminus nor block by tetraethylammonium alters the time course of inactivation. By incorporating the characteristics of Aplysia Shab into a computational model, we have shown how this current contributes to the normal enhancement of action potentials that occurs in the bag cell neurons at the onset of neuropeptide secretion.

  6. Action potential shape change in an electrically coupled network during propagation: a computer simulation.

    PubMed

    Buckingham, Steven D; Spencer, Andrew N

    2008-06-01

    We applied compartmental computer modeling to test a model of spike shape change in the jellyfish, Polyorchis penicillatus, to determine whether adaptive spike shortening can be attributed to the inactivation properties of a potassium channel. We modeled the jellyfish outer nerve-ring as a continuous linear segment, using ion channel and membrane properties derived in earlier studies. The model supported action potentials that shortened as they propagated away from the site of initiation and this was found to be largely independent of potassium channel inactivation. Spike broadening near the site of initiation was found to be due to a depolarization plateau that collapsed as two spikes spread from the point of initiation. The lifetime of this plateau was found to depend critically on the inward current flux and the space constant of the membrane. These data suggest that the spike shape changes may be due not only to potassium channel inactivation, but also to the passive properties of the membrane.

  7. 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.

  8. Inhomogeneity of action potential waveshape assists frequency entrainment of cardiac pacemaker cells.

    PubMed

    Cloherty, S L; Lovell, N H; Celler, B G; Dokos, S

    2001-10-01

    In this paper, we have employed ionic models of sinoatrial node cells to investigate the synchronization of a pair of coupled cardiac pacemaker cells from central and peripheral regions of the sinoatrial node. The free-running cycle length of the cell models was perturbed using two independent techniques and the minimum coupling conductance required to achieve frequency entrainment was used to assess the relative ease with which various cell pairs achieve entrainment. The factors effecting entrainment were further investigated using single-cell models paced with an artificial biphasic coupling current. Our simulation results suggest that dissimilar cell types, those with largely different upstroke velocities entrain more easily, that is, they require less coupling conductance to achieve 1:1 frequency entrainment. We, therefore, propose that regional variation in action-potential waveshape within the sinoatrial node assists frequency synchronization in vivo.

  9. Distributed computing for membrane-based modeling of action potential propagation.

    PubMed

    Porras, D; Rogers, J M; Smith, W M; Pollard, A E

    2000-08-01

    Action potential propagation simulations with physiologic membrane currents and macroscopic tissue dimensions are computationally expensive. We, therefore, analyzed distributed computing schemes to reduce execution time in workstation clusters by parallelizing solutions with message passing. Four schemes were considered in two-dimensional monodomain simulations with the Beeler-Reuter membrane equations. Parallel speedups measured with each scheme were compared to theoretical speedups, recognizing the relationship between speedup and code portions that executed serially. A data decomposition scheme based on total ionic current provided the best performance. Analysis of communication latencies in that scheme led to a load-balancing algorithm in which measured speedups at 89 +/- 2% and 75 +/- 8% of theoretical speedups were achieved in homogeneous and heterogeneous clusters of workstations. Speedups in this scheme with the Luo-Rudy dynamic membrane equations exceeded 3.0 with eight distributed workstations. Cluster speedups were comparable to those measured during parallel execution on a shared memory machine.

  10. 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.

  11. BDNF mRNA abundance regulated by antidromic action potentials and AP-LTD in hippocampus.

    PubMed

    Bukalo, Olena; Lee, Philip R; Fields, R Douglas

    2016-12-02

    Action-potential-induced LTD (AP-LTD) is a form of synaptic plasticity that reduces synaptic strength in CA1 hippocampal neurons firing antidromically during sharp-wave ripples. This firing occurs during slow-wave sleep and quiet moments of wakefulness, which are periods of offline replay of neural sequences learned during encoding sensory information. Here we report that rapid and persistent down-regulation of different mRNA transcripts of the BDNF gene accompanies AP-LTD, and that AP-LTD is abolished in mice with the BDNF gene knocked out in CA1 hippocampal neurons. These findings increase understanding of the mechanism of AP-LTD and the cellular mechanisms of memory consolidation.

  12. Sequential dissection of multiple ionic currents in single cardiac myocytes under action potential-clamp

    PubMed Central

    Banyasz, Tamas; Horvath, Balazs; Jian, Zhong; Izu, Leighton T.; Chen-Izu, Ye

    2011-01-01

    The cardiac action potential (AP) is shaped by myriad ionic currents. In this study we develop an innovative AP-clamp Sequential Dissection technique to enable recording of multiple ionic currents in the single cell under AP-clamp. This new technique presents a significant step beyond the traditional way of recording only one current in any one cell. The ability to measure many currents in a single cell has revealed two hitherto unknown characteristics of the ionic currents in cardiac cells: coordination of currents within a cell and large variation of currents between cells. Hence, the AP-clamp Sequential Dissection method provides a unique and powerful tool for studying individual cell electrophysiology. PMID:21215755

  13. Sequential dissection of multiple ionic currents in single cardiac myocytes under action potential-clamp.

    PubMed

    Banyasz, Tamas; Horvath, Balazs; Jian, Zhong; Izu, Leighton T; Chen-Izu, Ye

    2011-03-01

    The cardiac action potential (AP) is shaped by myriad ionic currents. In this study, we develop an innovative AP-clamp Sequential Dissection technique to enable the recording of multiple ionic currents in the single cell under AP-clamp. This new technique presents a significant step beyond the traditional way of recording only one current in any one cell. The ability to measure many currents in a single cell has revealed two hitherto unknown characteristics of the ionic currents in cardiac cells: coordination of currents within a cell and large variation of currents between cells. Hence, the AP-clamp Sequential Dissection method provides a unique and powerful tool for studying individual cell electrophysiology.

  14. 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

  15. Mechanism of alpha-2 adrenergic modulation of canine cardiac Purkinje action potential.

    PubMed

    Lee, H C; Cai, J J; Arnar, D O; Shibata, E F; Martins, J B

    1996-08-01

    We reported recently that stimulation of postjunctional alpha-2 adrenergic receptors prolongs the action potential durations (APD) of isolated canine Purkinje fibers. With standard microelectrode techniques, we examined the ionic mechanism through which alpha-2 adrenergic stimulation prolonged Purkinje APD, by measuring the effects of inhibitors of the various plateau currents on the alpha-2-mediated prolongation of APD. The alpha-2-specific agonist UK 14,304 (0.1 microM) prolonged the Purkinje APD at 50% repolarization and the APD at 90% repolarization, and these effects were inhibited by yohimbine (0.1 microM). The Purkinje APD at 50% repolarization and the APD at 90% repolarization were prolonged significantly with the transient outward potassium current inhibitor 4-aminopyridine (1 mM), the rapid component of delayed rectifier potassium current inhibitor d-sotalol (10 microM), the slow component of delayed rectifier potassium current inhibitor indapamide (0.1 microM) and the chloride current inhibitor mefenamic acid (10 nM) and were shortened significantly with the calcium current inhibitor nifedipine (0.3 microM). Prolongation of Purkinje APD at 50% repolarization and APD at 90% repolarization by UK 14,304 remained intact in the presence of d-sotalol, indapamide, mefenamic acid and nifedipine. All of these UK 14,304 effects were significantly reversed by yohimbine. Only in the presence of 4-aminopyridine did UK 14,304 fail to prolong Purkinje APD. The phase 1 magnitudes of Purkinje action potentials were also significantly inhibited by UK 14,304. This effect was completely abolished only in the presence of 4-aminopyridine. These results suggest that inhibition of the 4-aminopyridine-sensitive transient outward potassium current is the major ionic mechanism by which alpha-2 adrenergic stimulation prolongs Purkinje APD.

  16. 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

  17. Effects of norfluoxetine on the action potential and transmembrane ion currents in canine ventricular cardiomyocytes.

    PubMed

    Magyar, János; Szentandrássy, Norbert; Bányász, Tamás; Kecskeméti, Valéria; Nánási, Péter P

    2004-09-01

    Norfluoxetine is the most important active metabolite of the widely used antidepressant compound fluoxetine. Although the cellular electrophysiological actions of fluoxetine are well characterized in cardiac cells, little is known about the effects of its metabolite. In this study, therefore, the effects of norfluoxetine on action potential (AP) configuration and transmembrane ion currents were studied in isolated canine cardiomyocytes using the whole cell configuration of patch clamp techniques. Micromolar concentrations of norfluoxetine (1-10 microM) modified AP configuration: amplitude and duration of the AP and maximum velocity of depolarization were decreased in addition to depression of the plateau and elimination of the incisura of AP. Voltage clamp experiments revealed a concentration-dependent suppression of both L-type Ca(2+) current, I(Ca) (EC(50)=1.13+/-0.08 microM) and transient outward K(+) current, I(to) (EC(50)=1.19+/-0.17 microM) having Hill coefficients close to unity. The midpoint potential of the steady-state inactivation of I(Ca) was shifted from -20.9+/-0.75 mV to -27.7+/-1.35 mV by 3 microM norfluoxetine ( P<0.05, n=7). No such shift in the steady-state inactivation curve was observed in the case of I(to). Similarly, norfluoxetine caused no change in the steady-state current-voltage relationship of the membrane or in the density of the inward rectifier K(+) current, I(K1). All these effects of norfluoxetine developed rapidly and were fully reversible. Comparing present results with those obtained previously with fluoxetine, it can be concluded that norfluoxetine displays stronger suppression of cardiac ion channels than fluoxetine. Consequently, the majority of the cardiac side effects observed during fluoxetine treatment are likely to be attributed to its metabolite norfluoxetine.

  18. The potential economic impact of constructing and operating solar power generation facilities in Nevada

    SciTech Connect

    Schwer, R. K.; Riddel, M.

    2004-02-01

    Nevada has a vast potential for electricity generation using solar power. An examination of the stock of renewable resources in Nevada proves that the state has the potential to be a leader in renewable-electric generation--one of the best in the world. This study provides estimates on the economic impact in terms of employment, personal income, and gross state product (GSP) of developing a portion of Nevada's solar energy generation resources.

  19. Potential Economic Impact of Constructing and Operating Solar Power Generation Facilities in Nevada

    SciTech Connect

    Schwer, R. K.; Riddel, M.

    2004-02-01

    Nevada has a vast potential for electricity generation using solar power. An examination of the stock of renewable resources in Nevada proves that the state has the potential to be a leader in renewable-electric generation--one of the best in the world. This study provides estimates on the economic impact in terms of employment, personal income, and gross state product (GSP) of developing a portion of Nevada's solar energy generation resources.

  20. A sequence of flux transfer events potentially generated by different generation mechanisms

    NASA Astrophysics Data System (ADS)

    Trenchi, L.; Fear, R. C.; Trattner, K. J.; Mihaljcic, B.; Fazakerley, A. N.

    2016-09-01

    Flux transfer events (FTEs) are magnetic structures generated by time-varying reconnection at the dayside magnetopause. Understanding their generation mechanism is important, because it is necessary in order to understand the global contribution of FTEs to the convection process. We present observations of several FTEs sequentially observed by Cluster at the subsolar magnetopause. Cluster detected also several reconnection jets, which seem to be systematically associated with the trailing edge of the FTEs. This association is expected only in the FTEs formed by single X line reconnection but could be compatible also with the multiple X line model, when reconnection at one X line is dominant. Instead, it does not seem compatible with original mechanism proposed by Russell and Elphic (1978). For a large FTE, not associated with any reconnection jet, the Grad-Shafranov reconstruction obtained from Cluster 1 data recovers a flux rope, indicative of multiple X line reconnection. This same FTE was detected also by Cluster 3, which observed an asymmetric signature in the magnetic field component normal to the magnetopause. We show that this asymmetric signature was caused by an outward motion of the magnetopause. The orientation of the other FTEs, obtained from a Grad-Shafranov optimization, shows considerable spread, despite the relatively steady conditions. Our interpretation is that a combination of single and multiple X line reconnection generated these FTEs. The FTEs in the first part of the crossing, associated with reconnection jets, are generated by the single X line model and may therefore not satisfy the Grad-Shafranov assumptions so well. Instead, the last FTE, slower, bigger, and well separated from the previous ones, may be formed by multiple X line reconnection.

  1. Potential of an outranking multi-criteria approach to support the participatory assessment of land management actions.

    PubMed

    Ocampo-Melgar, Anahí; Bautista, Susana; Edward deSteiguer, J; Orr, Barron J

    2016-12-07

    We evaluated the potential of an outranking Multi-Criteria Decision Analysis approach for assisting in the participatory assessment of dryland management actions implemented in the San Simon watershed, in southeastern Arizona, USA. We compared an outranking-facilitated assessment of actions with a simple and direct (baseline) ranking of the same actions by the participating stakeholders in terms of: 1) internal homogeneity of each assessment approach, (2) similarity of individual assessments between methods, and (3) effects of the use of implicit/explicit assessment criteria. The actions assessed combined various management approaches, including livestock management (rotation, resting), vegetation management (grass seeding, brush control), and hydraulic structures (dams, dykes). The outranking-facilitated assessment discriminated better between actions and reduced the variability of results between individual stakeholders as compared with the direct ranking of actions. In general, the two assessments significantly differed in the relative preference of the five management actions assessed, yet both assessments identified rotational grazing combined with vegetation management (grass seeding and brush control) as the most preferred management action in the study area. The comparative analysis revealed inconsistencies between the use of implicit and explicit assessment criteria. Our findings highlight the opportunities offered by outranking approaches to help capture, structure, and make explicit stakeholder perspectives in the framework of a participatory environmental assessment process, which may facilitate the understanding of the multiple preferences involved. The outranking integration process, which resembles a voting procedure, proved simple and transparent, with potential for contributing to stakeholder engagement and trust in participatory assessment.

  2. Differential inhibitory action of apixaban on platelet and fibrin components of forming thrombi: Studies with circulating blood and in a platelet-based model of thrombin generation

    PubMed Central

    Arellano-Rodrigo, Eduardo; Reverter, Joan Carles; Lopez-Farre, Antonio; Diaz-Ricart, Maribel; Badimon, Juan Jose; Escolar, Gines

    2017-01-01

    Introduction Mechanisms of action of direct oral anticoagulants (DOAC) suggest a potential therapeutic use in the prevention of thrombotic complications in arterial territories. However, effects of DOACs on platelet activation and aggregation have not been explored in detail. We have investigated the effects of apixaban on platelet and fibrin components of thrombus formation under static and flow conditions. Methods We assessed the effects of apixaban (10, 40 and 160 ng/mL) on: 1) platelet deposition and fibrin formation onto a thrombogenic surface, with blood circulating at arterial shear-rates; 2) viscoelastic properties of forming clots, and 3) thrombin generation in a cell-model of coagulation primed by platelets. Results In studies with flowing blood, only the highest concentration of apixaban, equivalent to the therapeutic Cmax, was capable to significantly reduce thrombus formation, fibrin association and platelet-aggregate formation. Apixaban significantly prolonged thromboelastometry parameters, but did not affect clot firmness. Interestingly, results in a platelet-based model of thrombin generation under more static conditions, revealed a dose dependent persistent inhibitory action by apixaban, with concentrations 4 to 16 times below the therapeutic Cmax significantly prolonging kinetic parameters and reducing the total amount of thrombin generated. Conclusions Our studies demonstrate the critical impact of rheological conditions on the antithrombotic effects of apixaban. Studies under flow conditions combined with modified thrombin generation assays could help discriminating concentrations of apixaban that prevent excessive platelet accumulation, from those that deeply impair fibrin formation and may unnecessarily compromise hemostasis. PMID:28192448

  3. Action potential broadening induced by lithium may cause a presynaptic enhancement of excitatory synaptic transmission in neonatal rat hippocampus.

    PubMed

    Colino, A; García-Seoane, J J; Valentín, A

    1998-07-01

    Lithium enhances excitatory synaptic transmission in CA1 pyramidal cells, but the mechanisms remain unclear. The present study demonstrates that lithium enhances the N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-isoxazole propionic acid (AMPA) receptor-mediated components of the excitatory postsynaptic current (EPSC). Lithium decreased the magnitude of paired-pulse facilitation and presented an inverse correlation between the lithium-induced enhancement of synaptic transmission and initial paired-pulse facilitation, which is consistent with a presynaptic mode of action. The enhancement of synaptic strength is likely to act, at least in part, by increasing the amplitude of the presynaptic Ca2+ transient. One mechanism which could account for this change of the presynaptic Ca2+ transient is an increase in the duration of the action potential. We investigated action potential in hippocampal pyramidal neurons and found that lithium (0.5-6 mM) increased the half-amplitude duration and reduced the rate of repolarization, whereas the rate of depolarization remained similar. To find out whether the lithium synaptic effects might be explained by spike broadening, we investigated the field recording of the excitatory postsynaptic potential (EPSP) in hippocampal slices and found three lines of evidence. First, the prolongation of the presynaptic action potential with 4-aminopyridine and tetraethylammonium blocked or reduced the synaptic effects of lithium. Second, the lithium-induced synaptic enhancement was modulated when presynaptic Ca2+ influx was varied by changing the external Ca2+ concentration. Finally, both effects, the synaptic transmission increment and the action potential broadening, were independent of inositol depletion. These results suggest that lithium enhances synaptic transmission in the hippocampus via a presynaptic site of action: the mechanism underlying the potentiating effect may be attributable to an increased Ca2+ influx consequent

  4. Profile of I(Ks) during the action potential questions the therapeutic value of I(Ks) blockade.

    PubMed

    Bányász, Tamás; Koncz, Roland; Fülöp, László; Szentandrássy, Norbert; Magyar, János; Nánási, Péter P

    2004-01-01

    The goal of this paper is two fold. First, we attempt to review the reports available on the role of I(Ks) in myocardial repolarization. Based on theoretical considerations and experimental results, it seems reasonable to assume that I(Ks)blockade will lengthen the action potential. However, results obtained with I(Ks) blockers, like chromanol 293B or L-735,821, are conflicting, since from slight lengthening to marked prolongation of action potentials were equally obtained. Although these contradictory results were explained by interspecies or regional differences, the role of I(Ks) in repolarization is a matter of growing dispute. In the second part of this study, we simulated the performance of I(Ks) during cardiac action potentials. We compared the profile of the predicted current in three mathematical models in order to determine the relative role of the current in repolarization. We studied the effect of the cycle length, action potential duration and height of the plateau on the profile of I(Ks) in epicardiac, endocardiac and midmyocardiac ventricular action potentials. The results indicate that the height of the plateau is the most important parameter to control activation of I(Ks)in cardiac tissues, and accordingly, the interspecies and regional differences observed in the efficacy of I(Ks) blockers are likely due to the known differences in action potential morphology. We conclude also that I(Ks)blockade may have unpredictable effects on the length of the action potential in a diseased heart, questioning the possible therapeutic value of drugs blocking I(Ks).

  5. Bayesian Action-Perception loop modeling: Application to trajectory generation and recognition using internal motor simulation

    NASA Astrophysics Data System (ADS)

    Gilet, Estelle; Diard, Julien; Palluel-Germain, Richard; Bessière, Pierre

    2011-03-01

    This paper is about modeling perception-action loops and, more precisely, the study of the influence of motor knowledge during perception tasks. We use the Bayesian Action-Perception (BAP) model, which deals with the sensorimotor loop involved in reading and writing cursive isolated letters and includes an internal simulation of movement loop. By using this probabilistic model we simulate letter recognition, both with and without internal motor simulation. Comparison of their performance yields an experimental prediction, which we set forth.

  6. [Double action potentials in the command neurons of Helix pomatia in response to the action of cobalt ions].

    PubMed

    Palikhova, T A; Khludova, L K; Sokolov, E N

    1987-01-01

    Cobalt chloride (20 mmol/l) in physiological solution results in generation of doublets of spikes in Helix pomatia command neurons in response to intracellularly injected depolarizing current. The extraspikes arise in arborizations of neuron and are determined by influx sodium ions. It is supposed that facilitation of extraspikes in apparently due to long-lasting blockade of calcium-dependent potassium current by Co2+ ions.

  7. Analogue modulation of back-propagating action potentials enables dendritic hybrid signalling.

    PubMed

    Brunner, János; Szabadics, János

    2016-10-05

    We report that back-propagating action potentials (bAPs) are not simply digital feedback signals in dendrites but also carry analogue information about the overall state of neurons. Analogue information about the somatic membrane potential within a physiological range (from -78 to -64 mV) is retained by bAPs of dentate gyrus granule cells as different repolarization speeds in proximal dendrites and as different peak amplitudes in distal regions. These location-dependent waveform changes are reflected by local calcium influx, leading to proximal enhancement and distal attenuation during somatic hyperpolarization. The functional link between these retention and readout mechanisms of the analogue content of bAPs critically depends on high-voltage-activated, inactivating calcium channels. The hybrid bAP and calcium mechanisms report the phase of physiological somatic voltage fluctuations and modulate long-term synaptic plasticity in distal dendrites. Thus, bAPs are hybrid signals that relay somatic analogue information, which is detected by the dendrites in a location-dependent manner.

  8. Role of dendritic spines in action potential backpropagation: a numerical simulation study.

    PubMed

    Tsay, David; Yuste, Rafael

    2002-11-01

    Two remarkable aspects of pyramidal neurons are their complex dendritic morphologies and the abundant presence of spines, small structures that are the sites of excitatory input. Although the channel properties of the dendritic shaft membrane have been experimentally probed, the influence of spine properties in dendritic signaling and action potential propagation remains unclear. To explore this we have performed multi-compartmental numerical simulations investigating the degree of consistency between experimental data on dendritic channel densities and backpropagation behavior, as well as the necessity and degree of influence of excitable spines. Our results indicate that measured densities of Na(+) channels in dendritic shafts cannot support effective backpropagation observed in apical dendrites due to suprathreshold inactivation. We demonstrate as a potential solution that Na(+) channels in spines at higher densities than those measured in the dendritic shaft can support extensive backpropagation. In addition, clustering of Na(+) channels in spines appears to enhance their effect due to their unique morphology. Finally, we show that changes in spine morphology significantly influence backpropagation efficacy. These results suggest that, by clustering sodium channels, spines may serve to control backpropagation.

  9. Seasonal acclimatization of the cardiac action potential in the Arctic navaga cod (Eleginus navaga, Gadidae).

    PubMed

    Hassinen, Minna; Abramochkin, Denis V; Vornanen, Matti

    2014-04-01

    Freshwater fishes of north-temperate latitudes adjust electrical excitability of the heart to seasonal temperature changes by changing expression levels of ion channel isoforms. However, little is known about thermal responses of action potential (AP) in the hearts of marine polar fishes. To this end, we examined cardiac AP in the atrial myocardium of the Arctic navaga cod (Eleginus navaga) from the White Sea (Russia) acclimatized to winter (March) and summer (September) seasons. Acute increases in temperature from 4 to 10 °C were associated with increases in heart rate, maximum velocity of AP upstroke and negative resting membrane potential, while duration of AP was shortened in both winter-acclimatized and summer-acclimatized navaga hearts. In winter, there was a compensatory shortening (41.1%) of atrial AP duration and this was associated with a strong increase in transcript expression of Erg K(+) channels, known to produce the rapid component of the delayed rectifier K(+) current, I(Kr). Smaller increases were found in the expression of Kir2.1 channels that produce the inward rectifier K(+) current, I(K1). These findings indicate that the heart of navaga cod has a good acclimatory capacity in electrical excitation of cardiac myocytes, which enables cardiac function in the cold-eurythermal waters of the subarctic White Sea.

  10. 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

  11. 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.

  12. Zinc-related actions of sublethal levels of benzalkonium chloride: Potentiation of benzalkonium cytotoxicity by zinc.

    PubMed

    Mitani, Tsuyoshi; Elmarhomy, Ahmed Ibrahim Elhossany; Dulamjav, Luvsandorj; Anu, Enkhtumur; Saitoh, Shohei; Ishida, Shiro; Oyama, Yasuo

    2017-04-25

    Benzalkonium chloride (BZK) is a common preservative used in pharmaceutical and personal care products. ZnCl2 was recently reported to significantly potentiate the cytotoxicity of some biocidal compounds. In the present study, therefore, we compared the cytotoxic potency of BZK and then further studied the Zn(2+)-related actions of the most cytotoxic agent among BZK, using flow cytometric techniques with appropriate fluorescent probes in rat thymocytes. Cytotoxicity of benzylcetyldimethylammonium (BZK-C16) was more potent that those of benzyldodecyldimethylammonium and benzyldimethyltetradecylammonium. ZnCl2 (1-10 μM) significantly potentiated the cytotoxicity of BZK-C16 at a sublethal concentration (1 μM). The co-treatment of cells with 3 μM ZnCl2 and 1 μM BZK-C16 increased the population of both living cells with phosphatidylserine exposed on membrane surfaces and dead cells. BZK-C16 at 0.3-1.0 μM elevated intracellular Zn(2+) levels by increasing Zn(2+) influx, and augmented the cytotoxicity of 100 μM H2O2. Zn(2+) is concluded to facilitate the toxicity of BZK. We suggest that the toxicity of BZK is determined after taking extracellular (plasma) and/or environmental Zn(2+) levels into account.

  13. Glutamate induces series of action potentials and a decrease in circumnutation rate in Helianthus annuus.

    PubMed

    Stolarz, Maria; Król, Elzbieta; Dziubińska, Halina; Kurenda, Andrzej

    2010-03-01

    Reports concerning the function of glutamate (Glu) in the electrical and movement phenomena in plants are scarce. Using the method of extracellular measurement, we recorded electrical potential changes in the stem of 3-week-old Helianthus annuus L. plants after injection of Glu solution. Simultaneously, circumnutation movements of the stem were measured with the use of time-lapse images. Injection of Glu solution at millimolar (200, 50, 5 mM) concentrations in the basal part of the stem evoked a series of action potentials (APs). The APs appeared in the site of injection and in different parts of the stem and were propagated acropetally and/or basipetally along the stem. Glu injection also resulted in a transient, approximately 5-h-long decrease in the stem circumnutation rate. The APs initiated and propagating in the sunflower stem after Glu injection testify the existence of a Glu perception system in vascular plants and suggest its involvement in electrical, long-distance signaling. Our experiments also demonstrated that Glu is a factor affecting circumnutation movements.

  14. Analogue modulation of back-propagating action potentials enables dendritic hybrid signalling

    PubMed Central

    Brunner, János; Szabadics, János

    2016-01-01

    We report that back-propagating action potentials (bAPs) are not simply digital feedback signals in dendrites but also carry analogue information about the overall state of neurons. Analogue information about the somatic membrane potential within a physiological range (from −78 to −64 mV) is retained by bAPs of dentate gyrus granule cells as different repolarization speeds in proximal dendrites and as different peak amplitudes in distal regions. These location-dependent waveform changes are reflected by local calcium influx, leading to proximal enhancement and distal attenuation during somatic hyperpolarization. The functional link between these retention and readout mechanisms of the analogue content of bAPs critically depends on high-voltage-activated, inactivating calcium channels. The hybrid bAP and calcium mechanisms report the phase of physiological somatic voltage fluctuations and modulate long-term synaptic plasticity in distal dendrites. Thus, bAPs are hybrid signals that relay somatic analogue information, which is detected by the dendrites in a location-dependent manner. PMID:27703164

  15. A fluorescent, genetically-encoded voltage probe capable of resolving action potentials.

    PubMed

    Barnett, Lauren; Platisa, Jelena; Popovic, Marko; Pieribone, Vincent A; Hughes, Thomas

    2012-01-01

    There is a pressing need in neuroscience for genetically-encoded, fluorescent voltage probes that can be targeted to specific neurons and circuits to allow study of neural activity using fluorescent imaging. We created 90 constructs in which the voltage sensing portion (S1-S4) of Ciona intestinalis voltage sensitive phosphatase (CiVSP) was fused to circularly permuted eGFP. This led to ElectricPk, a probe that is an order of magnitude faster (taus ~1-2 ms) than any currently published fluorescent protein-based voltage probe. ElectricPk can follow the rise and fall of neuronal action potentials with a modest decrease in fluorescence intensity (~0.7% ΔF/F). The probe has a nearly linear fluorescence/membrane potential response to both hyperpolarizing and depolarizing steps. This is the first probe based on CiVSP that captures the rapid movements of the voltage sensor, suggesting that voltage probes designed with circularly permuted fluorescent proteins may have some advantages.

  16. Amplitudes of sural and radial sensory nerve action potentials in orthodromic and antidromic studies in children.

    PubMed

    Melendrez, J L; MacMillan, L J; Vajsar, J

    1998-01-01

    Several previous studies of adults have reported that the amplitudes of the sural and superficial radial nerve action potentials (SN and SRN SNAP respectively) are larger with antidromic than with orthodromic recordings. However, this difference has not been documented in children. This study evaluated the amplitudes of SN and SRN SNAPs obtained with antidromic and orthodromic recordings in children with and without neuropathy and compared these data with findings in adults. The SN or SRN or both of 10 neurologically normal children, 6 children with neuropathy and 7 healthy adults were studied with surface stimulation and recording. The position of the stimulating and recording electrodes for the orthodromic recordings was the reverse of that for the antidromic recordings. Peak-to-peak SNAP amplitudes were measured and analyzed. The mean of the SRN SNAP amplitude was significantly higher with the antidromic than the orthodromic technique for the first and third groups (p < 0.05). The mean SN SNAP amplitude was higher in the three groups, but not statistically significant when the data for the children and adult normal groups were combined and reanalyzed (p < 0.05). Consistent responses were obtained with both techniques. However, the antidromic technique was superior to the orthodromic technique because of the greater amplitude of responses. We recommend the use of the antidromic technique because of its greater amplitudes, ease of use and potential reduction of discomfort to the patient.

  17. 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

  18. Characterization of an early afterhyperpolarization after a brief train of action potentials in rat hippocampal neurons in vitro.

    PubMed

    Williamson, A; Alger, B E

    1990-01-01

    1. In rat hippocampal pyramidal cells in vitro, a brief train of action potentials elicited by direct depolarizing current pulses injected through an intracellular recording electrode is followed by a medium-duration afterhyperpolarization (mAHP) and a longer, slow AHP. We studied the mAHP with the use of current-clamp techniques in the presence of dibutyryl cyclic adenosine 3',5'-monophosphate (cAMP) to block the slow AHP and isolate the mAHP. 2. The mAHP evoked at hyperpolarized membrane potentials was complicated by a potential generated by the anomalous rectifier current, IQ. The mAHP is insensitive to chloride ions (Cl-), whereas it is sensitive to the extracellular potassium concentration ([K+]o). 3. At slightly depolarized levels, the mAHP is partially Ca2+ dependent, being enhanced by increased [Ca2+]o and BAY K 8644 and depressed by decreased [Ca2+]o, nifedipine, and Cd2+. The Ca2(+)-dependent component of the mAHP was also reduced by 100 microM tetraethylammonium (TEA) and charybdotoxin (CTX), suggesting it is mediated by the voltage- and Ca2(+)-dependent K+ current, IC. 4. Most of the Ca2(+)-independent mAHP was blocked by carbachol, implying that IM plays a major role. In a few cells, a small Ca2(+)- and carbachol-insensitive mAHP component was detectable, and this component was blocked by 10 mM TEA, suggesting it was mediated by the delayed rectifier current, IK. The K+ channel antagonist 4-aminopyridine (4-AP, 500 microM) did not reduce the mAHP. 5. We infer that the mAHP is a complex potential due either to IQ or to the combined effects of IM and IC. The contributions of each current depend on the recording conditions, with IC playing a role when the cells are activated from depolarized potentials and IM dominating at the usual resting potential. IQ is principally responsible for the mAHP recorded at hyperpolarized membrane potentials.

  19. Flavonoids, cognition, and dementia: actions, mechanisms, and potential therapeutic utility for Alzheimer disease.

    PubMed

    Williams, Robert J; Spencer, Jeremy P E

    2012-01-01

    There is increasing evidence that the consumption of flavonoid-rich foods can beneficially influence normal cognitive function. In addition, a growing number of flavonoids have been shown to inhibit the development of Alzheimer disease (AD)-like pathology and to reverse deficits in cognition in rodent models, suggestive of potential therapeutic utility in dementia. The actions of flavonoid-rich foods (e.g., green tea, blueberry, and cocoa) seem to be mediated by the direct interactions of absorbed flavonoids and their metabolites with a number of cellular and molecular targets. For example, their specific interactions within the ERK and PI3-kinase/Akt signaling pathways, at the level of receptors or kinases, have been shown to increase the expression of neuroprotective and neuromodulatory proteins and increase the number of, and strength of, connections between neurons. Concurrently, their effects on the vascular system may also lead to enhancements in cognitive performance through increased brain blood flow and an ability to initiate neurogenesis in the hippocampus. Additional mechanisms have been suggested for the ability of flavonoids to delay the initiation of and/or slow the progression of AD-like pathology and related neurodegenerative disorders, including a potential to inhibit neuronal apoptosis triggered by neurotoxic species (e.g., oxidative stress and neuroinflammation) or disrupt amyloid β aggregation and effects on amyloid precursor protein processing through the inhibition of β-secretase (BACE-1) and/or activation of α-secretase (ADAM10). Together, these processes act to maintain the number and quality of synaptic connections in key brain regions and thus flavonoids have the potential to prevent the progression of neurodegenerative pathologies and to promote cognitive performance.

  20. 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.

  1. Calcium‐activated chloride current determines action potential morphology during calcium alternans in atrial myocytes

    PubMed Central

    Kanaporis, Giedrius

    2016-01-01

    Key points Cardiac alternans – periodic beat‐to‐beat alternations in contraction, action potential (AP) morphology or cytosolic calcium transient (CaT) amplitude – is a high risk indicator for cardiac arrhythmias and sudden cardiac death. However, it remains an unresolved issue whether beat‐to‐beat alternations in intracellular Ca2+ ([Ca2+]i) or AP morphology are the primary cause of pro‐arrhythmic alternans.Here we show that in atria AP alternans occurs secondary to CaT alternans.CaT alternans leads to complex beat‐to‐beat changes in Ca2+‐regulated ion currents that determine alternans of AP morphology.We report the novel finding that alternans of AP morphology is largely sustained by the activity of Ca2+‐activated Cl− channels (CaCCs). Suppression of the CaCCs significantly reduces AP alternans, while CaT alternans remains unaffected.The demonstration of a major role of CaCCs in the development of AP alternans opens new possibilities for atrial alternans and arrhythmia prevention. Abstract Cardiac alternans, described as periodic beat‐to‐beat alternations in contraction, action potential (AP) morphology or cytosolic Ca transient (CaT) amplitude, is a high risk indicator for cardiac arrhythmias and sudden cardiac death. We investigated mechanisms of cardiac alternans in single rabbit atrial myocytes. CaTs were monitored simultaneously with membrane currents or APs recorded with the patch clamp technique. Beat‐to‐beat alternations of AP morphology and CaT amplitude revealed a strong quantitative correlation. Application of voltage clamp protocols in the form of pre‐recorded APs (AP‐clamp) during pacing‐induced CaT alternans revealed a Ca2+‐dependent current consisting of a large outward component (4.78 ± 0.58 pA pF–1 in amplitude) coinciding with AP phases 1 and 2 that was followed by an inward current (−0.42 ± 0.03 pA pF–1; n = 21) during AP repolarization. Approximately 90% of the initial outward current

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

    PubMed Central

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

    2009-01-01

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

  3. Earth & Space Science in the Next Generation Science Standards: Promise, Challenge, and Future Actions. (Invited)

    NASA Astrophysics Data System (ADS)

    Pyle, E. J.

    2013-12-01

    The Next Generation Science Standards (NGSS) are a step forward in ensuring that future generations of students become scientifically literate. The NGSS document builds from the National Science Education Standards (1996) and the National Assessment of Educational Progress (NAEP) science framework of 2005. Design teams for the Curriculum Framework for K-12 Science Education were to outline the essential content necessary for students' science literacy, considering the foundational knowledge and the structure of each discipline in the context of learning progressions. Once draft standards were developed, two issues emerged from their review: (a) the continual need to prune 'cherished ideas' within the content, such that only essential ideas were represented, and (b) the potential for prior conceptions of Science & Engineering Practices (SEP) and cross-cutting concepts (CCC) to limit overly constrain performance expectations. With the release of the NGSS, several challenges are emerging for geoscience education. First, the traditional emphasis of Earth science in middle school has been augmented by new standards for high school that require major syntheses of concepts. Second, the integration of SEPs into performance expectations places an increased burden on teachers and curriculum developers to organize instruction around the nature of inquiry in the geosciences. Third, work is needed to define CCCs in Earth contexts, such that the unique structure of the geosciences is best represented. To ensure that the Earth & Space Science standards are implemented through grade 12, two supporting structures must be developed. In the past, many curricular materials claimed that they adhered to the NSES, but in some cases this match was a simple word match or checklist that bore only superficial resemblance to the standards. The structure of the performance expectations is of sufficient sophistication to ensure that adherence to the standards more than a casual exercise. Claims

  4. Mechanism of potassium efflux and action potential shortening during ischaemia in isolated mammalian cardiac muscle.

    PubMed Central

    Gasser, R N; Vaughan-Jones, R D

    1990-01-01

    1. Ischaemia was simulated in the isolated sheep cardiac Purkinje fibre and guinea-pig papillary muscle by immersing the preparations in paraffin oil. Ion-selective microelectrodes recorded potassium (Ks+) and pH (pHs) in the thin film of Tyrode solution trapped at the fibre surface while other microelectrodes recorded intracellular pH (pHi), membrane potential and action potentials (AP) (evoked by field stimulation), or membrane current (two-microelectrode voltage clamp in shortened Purkinje fibres). Twitch tension was also monitored. The paraffin oil model reproduced the salient characteristics of myocardial ischaemia, i.e. a decrease of twitch tension; a decrease of pHi and pHs; a rise in Ks+ (by 2-3 mM); a depolarization of diastolic membrane potential; considerable shortening of the AP (up to 30% within 4 min). 2. The sulphonylurea compounds, glibenclamide (200 microM) and tolbutamide (1 mM), known inhibitors of the KATP channel, completely blocked the ischaemic rise of Ks+ and prevented AP shortening. Ischaemic tension decline was notably less pronounced in the presence of sulphonylureas. 3. The ischaemic increase of slope conductance (Purkinje fibre) was prevented by 1 mM-tolbutamide and 200 microM-glibenclamide. 4. Sulphonylureas did not affect resting membrane potential, the AP or the current-voltage relationship under non-ischaemic conditions (this also indicates that ischaemic Ks+ accumulation is not fuelled by the background K+ current [iK1] which was shown, as expected, to be Ba2+ sensitive). 5. In a normally perfused preparation, reducing intracellular ATP by inhibiting glycolysis with 2-deoxyglucose (DOG) produced a similar AP shortening plus a membrane hyperpolarization, both of which were inhibited by tolbutamide or glibenclamide. The AP shortening was not related uniquely to the fall of pHi observed under these conditions since experimentally reducing pHi (by reducing pHo in the absence of DOG) lengthened rather than shortened the AP. 6. The

  5. The generation of short-wave UV light in cells under the action of ultrashort pulses of intense visible radiation

    NASA Astrophysics Data System (ADS)

    Kovarsky, V. A.; Philipp, B. S.; Kovarsky, E. V.

    1997-02-01

    The action of intense laser pulses ( λ = 0.53 μm) on E.coli cells is considered (the cells are transparent in this range). The transformation of laser radiation into UV light due to the high-harmonics generation on the protein molecules (the dipole moment is 100-1000 D) leads to the appearance of thymine dimers in bacterial DNA and results in a lethal effect for strains of E.coli which are highly sensitive to UV radiation.

  6. Actions of the digitalis analogue strophanthidin on action potentials and L-type calcium current in single cells isolated from the rabbit atrioventricular node.

    PubMed Central

    Hancox, J. C.; Levi, A. J.

    1996-01-01

    1. The atrioventricular node (AVN) of the heart is vital to normal cardiac function and is a major site of antiarrhythmic drug action. This study describes the effects of the cardiac glycoside analogue strophanthidin on spontaneous action potentials and L-type calcium current recorded from single AVN cells isolated from the rabbit heart. 2. With a standard KCl-based internal dialysis solution, exposure to 50 microM strophanthidin produced a progressive depolarization of the maximum diastolic potential and a reduction in action potential amplitude and upstroke velocity. Sustained application resulted in the loss of action potentials and occurrence of spontaneous 'bell-shaped' depolarizations. 3. Cells were whole-cell voltage clamped at -40 mV and depolarizing voltage clamps applied. With a standard KCl-based internal dialysis solution, exposure to 50 microM strophanthidin caused a large reduction of ICa,L at all potentials between -30 and +40 mV (n = 4). At + 10 mV, the mean ICa,L amplitude was reduced from -232 +/- 65 pA to -48 +/- 26 pA (P < 0.05; 1 test; n = 5 cells). 4. To record ICa,L more selectively, cells were dialysed with a Cs-based pipette solution. A short strophanthidin exposure reduced ICa,L amplitude from -250 +/- 31 pA to -88 +/- 19 pA (P < 0.001; n = 8 cells). For both KCl and CsCl-based solutions it was observed that sustained exposure to strophanthidin for several minutes caused spontaneous inward fluctuations in the membrane current record similar to the 'ITI' (arrhythmogenic oscillatory transient inward) current shown for other cardiac cells. 5. When the calcium chelator BAPTA was added to the pipette solution (10 mM), the reduction in ICa,L by strophanthidin was largely eliminated (P > 0.1), and no spontaneous inward current fluctuations were observed after sustained exposure to strophanthidin (n = 8 cells). 6. When external Ca in the perfusate was replaced with Ba, strophanthidin did not significantly reduce the Ba current through L

  7. Action potential repolarization and a fast after-hyperpolarization in rat hippocampal pyramidal cells.

    PubMed

    Storm, J F

    1987-04-01

    1. The repolarization of the action potential, and a fast after-hyperpolarization (a.h.p.) were studied in CA1 pyramidal cells (n = 76) in rat hippocampal slices (28-37 degrees C). Single spikes were elicited by brief (1-3 ms) current pulses, at membrane potentials close to rest (-60 to -70 mV). 2. Each action potential was followed by four after-potentials: (a) the fast a.h.p., lasting 2-5 ms; (b) an after-depolarization; (c) a medium a.h.p., (50-100 ms); and (d) a slow a.h.p. (1-2 s). Both the fast a.h.p. and the slow a.h.p. (but not the medium a.h.p.) were inhibited by Ca2+-free medium or Ca2+-channel blockers (Co2+, Mn2+ or Cd2+); but tetraethylammonium (TEA; 0.5-2 nM) blocked only the fast a.h.p., and noradrenaline (2-5 microM) only the slow a.h.p. This suggests that two Ca2+-activated K+ currents were involved: a fast, TEA-sensitive one (IC) underlying the fast a.h.p., and a slow noradrenaline-sensitive one (IAHP) underlying the slow a.h.p. 3. Like the fast a.h.p., spike repolarization seems to depend on a Ca2+-dependent K+ current of the fast, TEA-sensitive kind (IC). The repolarization was slowed by Ca2+-free medium, Co2+, Mn2+, Cd2+, or TEA, but not by noradrenaline. Charybdotoxin (CTX; 30 nM), a scorpion toxin which blocks the large-conductance Ca2+-activated K+ channel in muscle, had a similar effect to TEA. The effects of TEA and Cd2+ (or Mn2+) showed mutual occlusion. Raising the external K+ concentration reduced the fast a.h.p. and slowed the spike repolarization, whereas Cl- loading of the cell was ineffective. 4. The transient K+ current, IA, seems also to contribute to spike repolarization, because: (a) 4-aminopyridine (4-AP; 0.1 mM), which blocks IA, slowed the spike repolarization; (b) depolarizing pre-pulses, which inactivate IA, had a similar effect; (c) hyperpolarizing pre-pulses speeded up the spike repolarization; (d) the effects of 4-AP and pre-pulses persisted during Ca2+ blockade (like IA); and (e) depolarizing pre-pulses reduced the

  8. Ca2+ imaging of mouse neocortical interneurone dendrites: Ia-type K+ channels control action potential backpropagation

    PubMed Central

    Goldberg, Jesse H; Tamas, Gabor; Yuste, Rafael

    2003-01-01

    GABAergic interneurones are essential in cortical processing, yet the functional properties of their dendrites are still poorly understood. In this first study, we combined two-photon calcium imaging with whole-cell recording and anatomical reconstructions to examine the calcium dynamics during action potential (AP) backpropagation in three types of V1 supragranular interneurones: parvalbumin-positive fast spikers (FS), calretinin-positive irregular spikers (IS), and adapting cells (AD). Somatically generated APs actively backpropagated into the dendritic tree and evoked instantaneous calcium accumulations. Although voltage-gated calcium channels were expressed throughout the dendritic arbor, calcium signals during backpropagation of both single APs and AP trains were restricted to proximal dendrites. This spatial control of AP backpropagation was mediated by Ia-type potassium currents and could be mitigated by by previous synaptic activity. Further, we observed supralinear summation of calcium signals in synaptically activated dendritic compartments. Together, these findings indicate that in interneurons, dendritic AP propagation is synaptically regulated. We propose that interneurones have a perisomatic and a distal dendritic functional compartment, with different integrative functions. PMID:12844506

  9. Neural recording front-end IC using action potential detection and analog buffer with digital delay for data compression.

    PubMed

    Liu, Lei; Yao, Lei; Zou, Xiaodan; Goh, Wang Ling; Je, Minkyu

    2013-01-01

    This paper presents a neural recording analog front-end IC intended for simultaneous neural recording with action potential (AP) detection for data compression in wireless multichannel neural implants. The proposed neural recording front-end IC detects the neural spikes and sends only the preserved AP information for wireless transmission in order to reduce the overall power consumption of the neural implant. The IC consists of a low-noise neural amplifier, an AP detection circuit and an analog buffer with digital delay. The neural amplifier makes use of a current-reuse technique to maximize the transconductance efficiency for attaining a good noise efficiency factor. The AP detection circuit uses an adaptive threshold voltage to generate an enable signal for the subsequent functional blocks. The analog buffer with digital delay is employed using a finite impulse response (FIR) filter which preserves the AP waveform before the enable signal as well as provides low-pass filtering. The neural recording front-end IC has been designed using standard CMOS 0.18-µm technology occupying a core area of 220 µm by 820 µm.

  10. 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

  11. The central action of salbutamol, a beta-agonist with a potential antidepressant activity.

    PubMed

    Przegalinski, E; Baran, L; Kedrek, G

    1980-01-01

    The pharmacological profile of salbutamol, an agonist of beta-adrenergic receptors and a potential antidepressant drug, and its effect on the central serotonin system were studied. It was found that salbutamol either had no effect, or, at higher doses, inhibited the spontaneous activity of mice and rats; it did not influence significantly either the produced by amphetamine locomotor stimulation (in mice and rats) or amphetamine stereotype (in rats). Salbutamol while not affecting body temperature of normal mice reversed hypothermia but not ptosis induced by reserpine, and counteracted the hypothermic action of apomorphine in mice. It neither affected the spiperone-induced catalepsy nor was active in the behavioural despair test in rats. Salbutamol had no effect either, on the fenfluramine-induced hyperthermia in rabbits, on the 5-hydroxytryptophan-induced head twitch reaction in mice, on the tryptamine-induced clonic convulsions of forepaw in rats on the flexor reflex in spinal rats, or on the quipazine- or fenfluramine-induced stimulation of this reflex. The above findings indicate that the pharmacological profile of salbutamol resembles that of classical imipramine-like antidepressant drugs to a very small extent and it does not affect the central serotonergic transmission.

  12. A new three-variable mathematical model of action potential propagation in cardiac tissue.

    NASA Astrophysics Data System (ADS)

    Fenton, Flavio; Karma, Alain

    1996-03-01

    Modeling the electrical activity of the heart, and the complex signaling patterns which underly dangerous arrhythmias such as tachycardia and fibrillation, requires a quantitative model of action potential (AP) propagation. At present, there exist detailed ionic models of the Hodgkin-Huxley form that accurately reproduce dynamical features of the AP at a single cell level (e.g. Luo-Rudy, 1994). However, such models are not computationally tractable to study propagation in two and three-dimensional tissues of many resistively coupled cells. At the other extreme, there exists generic models of excitable media, such as the well-known FitzHugh-Nagumo model, which are only qualitative and do not reproduce essential dynamical features of cardiac AP. A new three-variable model is introduced which bridges the gap between these two types of models. It reproduces quantitatively important `mesoscopic' dynamical properties which are specific to cardiac AP, namely restitution and dispersion. At the same time, it remains computationally tractable and makes it possible to study the effect of these properties on the initiation, dynamics, and stability of complex reentrant excitations in two and three dimensions. Preliminary numerical results of the effect of restitution and dispersion on two-dimensional reentry (i.e. spiral waves) are presented.

  13. '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.

  14. Effects of stochastic channel gating and distribution on the cardiac action potential.

    PubMed

    Lemay, Mathieu; de Lange, Enno; Kucera, Jan P

    2011-07-21

    Ion channels exhibit stochastic conformational changes determining their gating behavior. In addition, the process of protein turnover leads to a natural variability of the number of membrane and gap junctional channels. Nevertheless, in computational models, these two aspects are scarcely considered and their impacts are largely unknown. We investigated the effects of stochastic current fluctuations and channel distributions on action potential duration (APD), intercellular conduction delays (ICDs) and conduction blocks using a modified ventricular cell model (Rudy et al.) with Markovian formulations of the principal ion currents (to simulate their stochastic open-close gating behavior) and with channel counts drawn from Poisson distributions (to simulate their natural variability). In single cells, APD variability (coefficient of variation: 1.6% at BCL=1000ms) was essentially caused by stochastic channel gating of I(Ks), persistent I(Na) and I(Ca,L). In cell strands, ICD variability induced by stochastic channel gating and Poissonian channel distributions was low under normal conditions. Nonetheless, at low intercellular coupling levels, Poissonian gap junctional channel distribution resulted in a large ICD variability (coefficient of variation >20%), highly heterogeneous conduction patterns and conduction blocks. Therefore, the stochastic behavior of current fluctuations and channel distributions can contribute to the heterogeneity of conduction patterns and to conduction block, as observed previously in experiments in cardiac tissue with altered intercellular coupling.

  15. 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

    2015-12-17

    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.

  16. Direction-Selective Circuitry in Rat Retina Develops Independently of GABAergic, Cholinergic and Action Potential Activity

    PubMed Central

    He, Shigang

    2011-01-01

    The ON-OFF direction selective ganglion cells (DSGCs) in the mammalian retina code image motion by responding much more strongly to movement in one direction. They do so by receiving inhibitory inputs selectively from a particular sector of processes of the overlapping starburst amacrine cells, a type of retinal interneuron. The mechanisms of establishment and regulation of this selective connection are unknown. Here, we report that in the rat retina, the morphology, physiology of the ON-OFF DSGCs and the circuitry for coding motion directions develop normally with pharmacological blockade of GABAergic, cholinergic activity and/or action potentials for over two weeks from birth. With recent results demonstrating light independent formation of the retinal DS circuitry, our results strongly suggest the formation of the circuitry, i.e., the connections between the second and third order neurons in the visual system, can be genetically programmed, although emergence of direction selectivity in the visual cortex appears to require visual experience. PMID:21573161

  17. 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

    2015-09-17

    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.

  18. Frequency decoding of periodically timed action potentials through distinct activity patterns in a random neural network

    NASA Astrophysics Data System (ADS)

    Reichenbach, Tobias; Hudspeth, A. J.

    2012-11-01

    Frequency discrimination is a fundamental task of the auditory system. The mammalian inner ear, or cochlea, provides a place code in which different frequencies are detected at different spatial locations. However, a temporal code based on spike timing is also available: action potentials evoked in an auditory-nerve fiber by a low-frequency tone occur at a preferred phase of the stimulus—they exhibit phase locking—and thus provide temporal information about the tone's frequency. Humans employ this temporal information for discrimination of low frequencies. How might such temporal information be read out in the brain? Here we employ statistical and numerical methods to demonstrate that recurrent random neural networks in which connections between neurons introduce characteristic time delays, and in which neurons require temporally coinciding inputs for spike initiation, can perform sharp frequency discrimination when stimulated with phase-locked inputs. Although the frequency resolution achieved by such networks is limited by the noise in phase locking, the resolution for realistic values reaches the tiny frequency difference of 0.2% that has been measured in humans.

  19. Telemetry system for reliable recording of action potentials from freely moving rats.

    PubMed

    Hawley, Emerson S; Hargreaves, Eric L; Kubie, John L; Rivard, Bruno; Muller, Robert U

    2002-01-01

    Recording single cells from alert rats currently requires a cable to connect brain electrodes to the acquisition system. If no cable were necessary, a variety of interesting experiments would become possible, and the design of other experiments would be simplified. To eliminate the need for a cable we have developed a one-channel radiotelemetry system that is easily carried by a rat. This system transmits a signal that is reliable, highly accurate and can be detected over distances of > or = 20 m. The mobile part of the system has three components: (1) a headstage with built-in amplifiers that plugs into the connector for the electrode array on the rat's head; the headstage also incorporates a light-emitting diode (LED) used to track the rat's position; (2) a backpack that contains the transmitter and batteries (2 N cells); the backpack also provides additional amplification of the single cell signals; and (3) a short cable that connects the headstage to the backpack; the cable supplies power to the headstage amplifiers and the LED, and carries the physiological signals from the headstage to the backpack. By using a differential amplifier and recording between two brain microelectrodes the system can transmit action potential activity from two nearly independent sources. In a future improvement, two transmitters with different frequencies would be used telemeter signals from four microelectrodes simultaneously.

  20. Loss of Saltation and Presynaptic Action Potential Failure in Demyelinated Axons

    PubMed Central

    Hamada, Mustafa S.; Popovic, Marko A.; Kole, Maarten H. P.

    2017-01-01

    In cortical pyramidal neurons the presynaptic terminals controlling transmitter release are located along unmyelinated axon collaterals, far from the original action potential (AP) initiation site, the axon initial segment (AIS). Once initiated, APs will need to reliably propagate over long distances and regions of geometrical inhomogeneity like branch points (BPs) to rapidly depolarize the presynaptic terminals and confer temporally precise synaptic transmission. While axon pathologies such as demyelinating diseases are well established to impede the fidelity of AP propagation along internodes, to which extent myelin loss affects propagation along BPs and axon collaterals is not well understood. Here, using the cuprizone demyelination model, we performed optical voltage-sensitive dye (VSD) imaging from control and demyelinated layer 5 pyramidal neuron axons. In the main axon, we find that myelin loss switches the modality of AP propagation from rapid saltation towards a slow continuous wave. The duration of single AP waveforms at BPs or nodes was, however, only slightly briefer. In contrast, by using two-photon microscopy-guided loose-seal patch recordings from axon collaterals we revealed a presynaptic AP broadening in combination with a reduced velocity and frequency-dependent failure. Finally, internodal myelin loss was also associated with de novo sprouting of axon collaterals starting from the primary (demyelinated) axon. Thus, the loss of oligodendrocytes and myelin sheaths bears functional consequences beyond the main axon, impeding the temporal fidelity of presynaptic APs and affecting the functional and structural organization of synaptic connectivity within the neocortex. PMID:28289377

  1. 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.

  2. Wavelet transform for real-time detection of action potentials in neural signals.

    PubMed

    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.

  3. A regenerative microchannel device for recording multiple single-unit action potentials in awake, ambulatory animals.

    PubMed

    Srinivasan, Akhil; Tipton, John; Tahilramani, Mayank; Kharbouch, Adel; Gaupp, Eric; Song, Chao; Venkataraman, Poornima; Falcone, Jessica; Lacour, Stéphanie P; Stanley, Garrett B; English, Arthur W; Bellamkonda, Ravi V

    2016-02-01

    Despite significant advances in robotics, commercially advanced prosthetics provide only a small fraction of the functionality of the amputated limb that they are meant to replace. Peripheral nerve interfacing could provide a rich controlling link between the body and these advanced prosthetics in order to increase their overall utility. Here, we report on the development of a fully integrated regenerative microchannel interface with 30 microelectrodes and signal extraction capabilities enabling evaluation in an awake and ambulatory rat animal model. In vitro functional testing validated the capability of the microelectrodes to record neural signals similar in size and nature to those that occur in vivo. In vitro dorsal root ganglia cultures revealed striking cytocompatibility of the microchannel interface. Finally, in vivo, the microchannel interface was successfully used to record a multitude of single-unit action potentials through 63% of the integrated microelectrodes at the early time point of 3 weeks. This marks a significant advance in microchannel interfacing, demonstrating the capability of microchannels to be used for peripheral nerve interfacing.

  4. Effects of aminoglycoside antibiotics on calcium action potentials and calcium channel currents.

    PubMed

    Suarez-Kurtz, G

    1989-01-01

    The author reviews work from his laboratory on the effects of neomycin and streptomycin on the Ca(2+)-dependent electrogenesis of crustacean muscle fibers and on two distinct Ca2+ channel currents of pituitary cells. The data indicate that these aminoglycosides inhibit the graded electrogenesis and the action potentials of crustacean muscle; these effects are accompanied by inhibition of tension development upon membrane depolarization. Increasing the extracellular Ca2+ concentration reverses the aminoglycoside-induced blockade of the Ca(2+)-dependent electrogenesis of the muscle fibers. Neomycin blocked both the transient (T-type) and the slowly-inactivating (L-type) Ca2+ currents of clonal pituitary GH3 cells, studied with the whole cell modality of the patch clamp technique. The blockade of these currents was not modulated by activation or inactivation of the channels. Neomycin inhibited also the currents conveyed by Na+ through the slowly-inactivating Ca2+ in cells equilibrated with Ca(2+)-free media. Interpretation of these data led to the suggestion that the blockade of Ca2+ currents by neomycin (and other aminoglycosides) cannot be explained by competition with Ca2+ ions for binding to high affinity transition sites within the Ca2+ channel path.

  5. Covariation of axon initial segment location and dendritic tree normalizes the somatic action potential

    PubMed Central

    Hamada, Mustafa S.; Goethals, Sarah; de Vries, Sharon I.; Brette, Romain

    2016-01-01

    In mammalian neurons, the axon initial segment (AIS) electrically connects the somatodendritic compartment with the axon and converts the incoming synaptic voltage changes into a temporally precise action potential (AP) output code. Although axons often emanate directly from the soma, they may also originate more distally from a dendrite, the implications of which are not well-understood. Here, we show that one-third of the thick-tufted layer 5 pyramidal neurons have an axon originating from a dendrite and are characterized by a reduced dendritic complexity and thinner main apical dendrite. Unexpectedly, the rising phase of somatic APs is electrically indistinguishable between neurons with a somatic or a dendritic axon origin. Cable analysis of the neurons indicated that the axonal axial current is inversely proportional to the AIS distance, denoting the path length between the soma and the start of the AIS, and to produce invariant somatic APs, it must scale with the local somatodendritic capacitance. In agreement, AIS distance inversely correlates with the apical dendrite diameter, and model simulations confirmed that the covariation suffices to normalize the somatic AP waveform. Therefore, in pyramidal neurons, the AIS location is finely tuned with the somatodendritic capacitive load, serving as a homeostatic regulation of the somatic AP in the face of diverse neuronal morphologies. PMID:27930291

  6. Ionic mechanisms underlying human atrial action potential properties: insights from a mathematical model.

    PubMed

    Courtemanche, M; Ramirez, R J; Nattel, S

    1998-07-01

    The mechanisms underlying many important properties of the human atrial action potential (AP) are poorly understood. Using specific formulations of the K+, Na+, and Ca2+ currents based on data recorded from human atrial myocytes, along with representations of pump, exchange, and background currents, we developed a mathematical model of the AP. The model AP resembles APs recorded from human atrial samples and responds to rate changes, L-type Ca2+ current blockade, Na+/Ca2+ exchanger inhibition, and variations in transient outward current amplitude in a fashion similar to experimental recordings. Rate-dependent adaptation of AP duration, an important determinant of susceptibility to atrial fibrillation, was attributable to incomplete L-type Ca2+ current recovery from inactivation and incomplete delayed rectifier current deactivation at rapid rates. Experimental observations of variable AP morphology could be accounted for by changes in transient outward current density, as suggested experimentally. We conclude that this mathematical model of the human atrial AP reproduces a variety of observed AP behaviors and provides insights into the mechanisms of clinically important AP properties.

  7. Quantitative weight of evidence to assess confidence in potential modes of action.

    PubMed

    Becker, Richard A; Dellarco, Vicki; Seed, Jennifer; Kronenberg, Joel M; Meek, Bette; Foreman, Jennifer; Palermo, Christine; Kirman, Chris; Linkov, Igor; Schoeny, Rita; Dourson, Michael; Pottenger, Lynn H; Manibusan, Mary K

    2017-02-20

    The evolved World Health Organization/International Programme on Chemical Safety mode of action (MOA) framework provides a structure for evaluating evidence in pathways of causally linked key events (KE) leading to adverse health effects. Although employed globally, variability in use of the MOA framework has led to different interpretations of the sufficiency of evidence in support of hypothesized MOAs. A proof of concept extension of the MOA framework is proposed for scoring confidence in the supporting data to improve scientific justification for MOA use in characterizing hazards and selecting dose-response extrapolation methods for specific chemicals. This involves selecting hypothesized MOAs, and then, for each MOA, scoring the weight of evidence (WOE) in support of causality for each KE using evolved Bradford Hill causal considerations (biological plausibility, essentiality, dose-response concordance, consistency, and analogy). This early proof of concept method is demonstrated by comparing two potential MOAs (mutagenicity and peroxisome proliferator activated receptor-alpha) for clofibrate, a rodent liver carcinogen. Quantitative confidence scoring of hypothesized MOAs is shown to be useful in characterizing the likely operative MOA. To guide method refinement and future confidence scoring for a spectrum of MOAs, areas warranting further focus and lessons learned, including the need to incorporate a narrative discussion of the weights used in the evaluation and an overall evaluation of the plausibility of the outcome, are presented.

  8. Low Somatic Sodium Conductance Enhances Action Potential Precision in Time-Coding Auditory Neurons.

    PubMed

    Yang, Yang; Ramamurthy, Bina; Neef, Andreas; Xu-Friedman, Matthew A

    2016-11-23

    Auditory nerve fibers encode sounds in the precise timing of action potentials (APs), which is used for such computations as sound localization. Timing information is relayed through several cell types in the auditory brainstem that share an unusual property: their APs are not overshooting, suggesting that the cells have very low somatic sodium conductance (gNa). However, it is not clear how gNa influences temporal precision. We addressed this by comparing bushy cells (BCs) in the mouse cochlear nucleus with T-stellate cells (SCs), which do have normal overshooting APs. BCs play a central role in both relaying and refining precise timing information from the auditory nerve, whereas SCs discard precise timing information and encode the envelope of sound amplitude. Nucleated-patch recording at near-physiological temperature indicated that the Na current density was 62% lower in BCs, and the voltage dependence of gNa inactivation was 13 mV hyperpolarized compared with SCs. We endowed BCs with SC-like gNa using two-electrode dynamic clamp and found that synaptic activity at physiologically relevant rates elicited APs with significantly lower probability, through increased activation of delayed rectifier channels. In addition, for two near-simultaneous synaptic inputs, the window of coincidence detection widened significantly with increasing gNa, indicating that refinement of temporal information by BCs is degraded by gNa Thus, reduced somatic gNa appears to be an adaption for enhancing fidelity and precision in time-coding neurons.

  9. Optical magnetic detection of single-neuron action potentials using quantum defects in diamond

    PubMed Central

    Barry, John F.; Turner, Matthew J.; Schloss, Jennifer M.; Glenn, David R.; Song, Yuyu; Lukin, Mikhail D.; Park, Hongkun; Walsworth, Ronald L.

    2016-01-01

    Magnetic fields from neuronal action potentials (APs) pass largely unperturbed through biological tissue, allowing magnetic measurements of AP dynamics to be performed extracellularly or even outside intact organisms. To date, however, magnetic techniques for sensing neuronal activity have either operated at the macroscale with coarse spatial and/or temporal resolution—e.g., magnetic resonance imaging methods and magnetoencephalography—or been restricted to biophysics studies of excised neurons probed with cryogenic or bulky detectors that do not provide single-neuron spatial resolution and are not scalable to functional networks or intact organisms. Here, we show that AP magnetic sensing can be realized with both single-neuron sensitivity and intact organism applicability using optically probed nitrogen-vacancy (NV) quantum defects in diamond, operated under ambient conditions and with the NV diamond sensor in close proximity (∼10 µm) to the biological sample. We demonstrate this method for excised single neurons from marine worm and squid, and then exterior to intact, optically opaque marine worms for extended periods and with no observed adverse effect on the animal. NV diamond magnetometry is noninvasive and label-free and does not cause photodamage. The method provides precise measurement of AP waveforms from individual neurons, as well as magnetic field correlates of the AP conduction velocity, and directly determines the AP propagation direction through the inherent sensitivity of NVs to the associated AP magnetic field vector. PMID:27911765

  10. Effects of terpineol on the compound action potential of the rat sciatic nerve.

    PubMed

    Moreira, M R; Cruz, G M; Lopes, M S; Albuquerque, A A; Leal-Cardoso, J H

    2001-10-01

    Terpineol, a volatile terpenoid alcohol of low toxicity, is widely used in the perfumery industry. It is an important chemical constituent of the essential oil of many plants with widespread applications in folk medicine and in aromatherapy. The effects of terpineol on the compound action potential (CAP) of rat sciatic nerve were studied. Terpineol induced a dose-dependent blockade of the CAP. At 100 microM, terpineol had no demonstrable effect. At 300 microM terpineol, peak-to-peak amplitude and conduction velocity of CAP were significantly reduced at the end of 180-min exposure of the nerve to the drug, from 3.28 +/- 0.22 mV and 33.5 +/- 7.05 m/s, respectively, to 1.91 +/- 0.51 mV and 26.2 +/- 4.55 m/s. At 600 microM, terpineol significantly reduced peak-to-peak amplitude and conduction velocity from 2.97 +/- 0.55 mV and 32.8 +/- 3.91 m/s to 0.24 +/- 0.23 mV and 2.72 +/- 2.72 m/s, respectively (N = 5). All these effects developed slowly and were reversible upon 180-min washout.

  11. 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

  12. The influence of passband limitation on the waveform of extracellular action potential.

    PubMed

    Mizuhiki, Takashi; Inaba, Kiyonori; Setogawa, Tsuyoshi; Toda, Koji; Ozaki, Shigeru; Shidara, Muneteka

    2012-03-01

    The duration of the extracellular action potential (EAP) in single neuronal recording has often been used as a clue to infer biochemical, physiological or functional substrate of the recorded neurons, e.g. neurochemical type. However, when recording a neuronal activity, the high-pass filter is routinely used to achieve higher signal-to-noise ratio. Signal processing theory predicts that passband limitation stretches the waveform of discrete brief impulse. To examine whether the duration of filtered EAP could be the reliable measure, we investigated the influence of high-pass filter both by simulation and unfiltered unit recording data from monkey dorsal raphe. Consistent with the findings in recent theoretical study, the unfiltered EAPs displayed the sharp wave without following bumps. The duration of unfiltered EAP was not correlated with that of filtered EAP. Thus the duration of original EAP cannot be estimated from filtered EAP. It is needed to reexamine the EAP duration measured for classifying the neurons whose activities were recorded under the passband limitation in the related studies.

  13. 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

  14. Modulation of action potential trains in rabbit saphenous nerve unmyelinated fibers.

    PubMed

    Zhu, Zhi-Ru; Liu, Yi-Hui; Ji, Wei-Gang; Duan, Jian-Hong; Hu, San-Jue

    2013-01-01

    Usually, the main axon is assumed to faithfully conduct action potentials (APs). Recent data have indicated that neural processing can occur along the axonal path. However, the patterns and mechanisms of temporal coding are not clear. In the present study, single fiber recording was used to analyze activity-dependent modulation of AP trains in the main axons of C fibers in the rabbit saphenous nerve. Trains of 5 superthreshold electrical pulses at interstimulus intervals of 20 or 50 ms were applied to the nerve trunk for 200 s. The interspike intervals (ISIs) for these trains were compared to the input interstimulus intervals. Three basic types of C fibers were observed in response to repeated stimuli: first, the ISI between the first and second AP (ISI1-2) of type 1 was longer than the interstimulus interval; second, the ISI1-2 of type 2 showed wavelike fluctuations around the interstimulus interval, and third, the ISI1-2 of type 3 exhibited shorter intervals for a long period. Furthermore, both 4-aminopyridine-sensitive potassium and hyperpolarization-activated cation currents were involved in the modulation of ISI1-2 of train pulses. These data provide new evidence that multiple modes of neural conduction can occur along the main axons of C fibers.

  15. 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

  16. 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

    2016-02-08

    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.

  17. 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

  18. Effect of rapid delayed rectifier current on hysteresis in restitution of action potential duration in swine.

    PubMed

    Agarwal, Anuj; Jing, Linyuan; Patwardhan, Abhijit

    2012-01-01

    Electrical stability in the heart depends on two important factors; restitution of action potential duration (APD) and memory. Repolarization currents play an important role in determining APD and also affect memory. We determined the effects of blocking the rapid component of the delayed rectifier (I(Kr)) on a quantifiable measure of memory, i.e. hysteresis in restitution of APD, in swine. Transmembrane potentials were recorded from right ventricular endocardial tissues. Two pacing protocols with explicit control of diastolic interval (DI) were used to change DIs in a sequential and sinusoidal pattern to quantify hysteresis in restitution of APD. E-4031 (5 µM/L) was used to block I(Kr). Measures of memory and restitution were quantified by calculating hysteresis loop thickness, area, overall tilt, and maximum and minimum delays between DIs and APDs. Blocking I(Kr) with E-4031 increased the baseline APD, loop thickness, area, and tilt (p<0.05). However, loop thickness did not increase beyond what could be predicted by the increase in baseline APD after block of I(Kr). The substantial change in APD after blocking I(Kr) suggests that this current plays a major role in repolarization in the swine. Loop thickness is a measure of memory, an increase in which is predicted by theory to reduce instability in activation. In our study, the substantial increase in loop thickness could be accounted for by an equally substantial increase in APD and therefore does not necessarily indicate increased memory after blocking I(Kr). Our results also suggest that factors based on restitution and memory need to be considered in the context of operating point, i.e. baseline APD, when they are used to explore mechanisms that affect electrical stability in the heart.

  19. Acetylcholinesterase antagonist potentiated insulin action in fed but not fasted state.

    PubMed

    Schafer, Joshua; Legare, Dallas J; Lautt, W Wayne

    2010-05-01

    The glucose disposal effect of insulin is doubled in response to a meal. This meal-induced insulin sensitization results from insulin acting on the liver, in the presence of a permissive hepatic parasympathetic feeding signal and elevated hepatic glutathione (GSH), to release hepatic insulin-sensitizing substance (HISS), a hormone that acts selectively on skeletal muscle to stimulate insulin-mediated glucose uptake. Blockade of the parasympathetic feeding signal to the liver, either through surgical denervation or atropine-mediated antagonism of hepatic muscarinic receptors, eliminates the HISS response, resulting in HISS-dependent insulin resistance (HDIR) and decreasing the response to insulin by approximately 55% in the fed state. Insulin action in Sprague-Dawley rats, as determined with a rapidly sampled, transient euglycemic clamp in response to insulin (50 mU/kg), is decreased in a dose-dependent manner by atropine. In this study, we have used the ED75 atropine-induced model of HDIR. After a submaximal dose of atropine, potentiation of the remaining parasympathetic effect with the acetylcholinesterase antagonist neostigmine significantly restored postprandial insulin sensitization in a dose-dependent manner with peak effect at 0.1 microg/kg/min. Neostigmine reversed the insulin resistance induced by partial fasting and partial muscarinic inhibition (hepatic GSH levels are at fed levels), but not that induced by surgical hepatic denervation (GSH normal, no nerve signal) or 24-h fasting (low GSH). No potentiation of the response to insulin by neostigmine occurred in normal, fed rats. The data suggest the use of either direct or indirectly acting cholinergic agonists for the treatment of impaired postprandial insulin sensitization.

  20. Molecular actions and therapeutic potential of lithium in preclinical and clinical studies of CNS disorders

    PubMed Central

    Chiu, Chi-Tso; Chuang, De-Maw

    2011-01-01

    Lithium has been used clinically to treat bipolar disorder for over half a century, and remains a fundamental pharmacological therapy for patients with this illness. Although lithium’s therapeutic mechanisms are not fully understood, substantial in vitro and in vivo evidence suggests that it has neuroprotective/neurotrophic properties against various insults, and considerable clinical potential for the treatment of several neurodegenerative conditions. Evidence from pharmacological and gene manipulation studies support the notion that glycogen synthase kinase-3 inhibition and induction of brain-derived neurotrophic factor-mediated signaling are lithium’s main mechanisms of action, leading to enhanced cell survival pathways and alteration of a wide variety of downstream effectors. By inhibiting N-methyl-D-aspartate receptor-mediated calcium influx, lithium also contributes to calcium homeostasis and suppresses calcium-dependent activation of pro-apoptotic signaling pathways. In addition, lithium decreases inositol 1,4,5-trisphosphate by inhibiting phosphoinositol phosphatases, a process recently identified as a novel mechanism for inducing autophagy. Through these mechanisms, therapeutic doses of lithium have been demonstrated to defend neuronal cells against diverse forms of death insults and to improve behavioral as well as cognitive deficits in various animal models of neurodegenerative diseases, including stroke, amyotrophic lateral sclerosis, fragile X syndrome, as well as Huntington’s, Alzheimer’s, and Parkinson’s diseases, among others. Several clinical trials are also underway to assess the therapeutic effects of lithium for treating these disorders. This article reviews the most recent findings regarding the potential targets involved in lithium’s neuroprotective effects, and the implication of these findings for the treatment of a variety of diseases. PMID:20705090

  1. 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.

  2. Burst analysis tool for developing neuronal networks exhibiting highly varying action potential dynamics.

    PubMed

    Kapucu, Fikret E; Tanskanen, Jarno M A; Mikkonen, Jarno E; Ylä-Outinen, Laura; Narkilahti, Susanna; Hyttinen, Jari A K

    2012-01-01

    In this paper we propose a firing statistics based neuronal network burst detection algorithm for neuronal networks exhibiting highly variable action potential dynamics. Electrical activity of neuronal networks is generally analyzed by the occurrences of spikes and bursts both in time and space. Commonly accepted analysis tools employ burst detection algorithms based on predefined criteria. However, maturing neuronal networks, such as those originating from human embryonic stem cells (hESCs), exhibit highly variable network structure and time-varying dynamics. To explore the developing burst/spike activities of such networks, we propose a burst detection algorithm which utilizes the firing statistics based on interspike interval (ISI) histograms. Moreover, the algorithm calculates ISI thresholds for burst spikes as well as for pre-burst spikes and burst tails by evaluating the cumulative moving average (CMA) and skewness of the ISI histogram. Because of the adaptive nature of the proposed algorithm, its analysis power is not limited by the type of neuronal cell network at hand. We demonstrate the functionality of our algorithm with two different types of microelectrode array (MEA) data recorded from spontaneously active hESC-derived neuronal cell networks. The same data was also analyzed by two commonly employed burst detection algorithms and the differences in burst detection results are illustrated. The results demonstrate that our method is both adaptive to the firing statistics of the network and yields successful burst detection from the data. In conclusion, the proposed method is a potential tool for analyzing of hESC-derived neuronal cell networks and thus can be utilized in studies aiming to understand the development and functioning of human neuronal networks and as an analysis tool for in vitro drug screening and neurotoxicity assays.

  3. Bringing Installation Art to Reconnaissance to Share Values and Generate Action

    ERIC Educational Resources Information Center

    Townsend, Andrew; Thomson, Pat

    2015-01-01

    The English education system has recently seen something of a revival of enthusiasm for the use of research both to develop educational practices and to gather evidence about their effectiveness. These initiatives often present action research as a model of individual problem-solving, which, we argue, communicates a limited conception of action…

  4. Practice Makes Perfect: Classrooms and Curricula That Generate Civic Minds and Actions

    ERIC Educational Resources Information Center

    Stanton, Timothy K.

    2014-01-01

    I propose an approach to service-learning that encourages and enables students to engage with human rights and social justice in ways that are democratic and effective. I describe a teaching process in which civic action can be critically reflected on not just to promote engagement and build knowledge but ultimately to encourage and equip students…

  5. Leaders Behaving Badly: Using Power to Generate Undiscussables in Action Learning Sets

    ERIC Educational Resources Information Center

    Donovan, Paul Jeffrey

    2014-01-01

    "Undiscussables" are topics associated with threat or embarrassment that are avoided by groups, where that avoidance is also not discussed. Their deleterious effect on executive groups has been a point of discussion for several decades. More recently critical action learning (AL) has brought a welcome focus to power relations within AL…

  6. Applying Knowledge to Generate Action: A Community-Based Knowledge Translation Framework

    ERIC Educational Resources Information Center

    Campbell, Barbara

    2010-01-01

    Introduction: Practical strategies are needed to translate research knowledge between researchers and users into action. For effective translation to occur, researchers and users should partner during the research process, recognizing the impact that knowledge, when translated into practice, will have on those most affected by that research.…

  7. Educational Action Research to Generate Ecological Wisdom of Insight for Inclusion and Sustainability

    ERIC Educational Resources Information Center

    Gedžune, Inga; Gedžune, Ginta; Skrinda, Astrida; Micule, Ilona

    2011-01-01

    This study relates the experience of educational action research with pre-service teachers aimed at exploring their views on ecological identity, which is considered the basis for a person's life activity, and its orientation towards inclusion in or exclusion from the global community of life. Through gradual opening of communicative space and…

  8. Bridging the Generation Gap: "Growing Golf" through an Action Learning Activity

    ERIC Educational Resources Information Center

    Elbert, Norb; Cumiskey, Kevin J.

    2014-01-01

    This paper describes an action learning simulation designed for a Professional Golf Management (PGM) program housed in a College of Business of a public university. The PGA Golf Management University Program, a 4.5- to 5-year college curriculum for aspiring PGA Professionals is offered at 19 PGA accredited universities nationwide. The program…

  9. The effects of ventricular end-diastolic and systolic pressures on action potential and duration in anaesthetized dogs.

    PubMed Central

    Coulshed, D S; Cowan, J C; Drinkhill, M J; Hainsworth, R

    1992-01-01

    1. Although it is known that mechanical events in the heart influence the duration of the cardiac action potential, there is no quantitative information on the effects of independent changes in ventricular end-diastolic and systolic pressures. 2. Experiments were carried out on open-chest anaesthetized dogs in which the autonomic nervous influences on the heart were prevented and monophasic action potentials were recorded form the epicardial surface of the left ventricle. The duration of these action potentials was taken as the interval from the upstroke to the point of 90% repolarization. 3. Elevation of left ventricular peak systolic pressure, at constant end-diastolic pressure, significantly shortened the monophasic action potential. 4. Elevation of end-diastolic pressure at constant peak systolic pressure significantly lengthened the monophasic action potential. 5. Responses were not dependent on release of noradrenaline from sympathetic nerve terminals because they persisted after administration of bretylium tosylate. They were also not due to myocardial ischaemia because they persisted when coronary perfusion pressure was maintained at a constant high level. 6. Simultaneous recordings of changes in myocardial segment length showed the expected responses to changes in ventricular pressures: increases in shortening in response to increases in diastolic pressure and no consistent effect from changes in systolic pressure. 7. These investigations demonstrate the independent effects of changes in systolic and end-diastolic pressures on cardiac action potential duration. This effect is likely to be an effect of the mechanical events, i.e. contraction-excitation feedback. This response may be mediated through changes in myocardial fibre tension, the consequent changes in fibre shortening, or both. PMID:1297849

  10. Atria selective prolongation by NIP-142, an antiarrhythmic agent, of refractory period and action potential duration in guinea pig myocardium.

    PubMed

    Matsuda, Tomoyuki; Takeda, Kentaro; Ito, Mie; Yamagishi, Reiko; Tamura, Miku; Nakamura, Hideki; Tsuruoka, Noriko; Saito, Tomoaki; Masumiya, Haruko; Suzuki, Takeshi; Iida-Tanaka, Naoko; Itokawa-Matsuda, Maho; Yamashita, Toru; Tsuruzoe, Nobutomo; Tanaka, Hikaru; Shigenobu, Koki

    2005-05-01

    NIP-142 is a novel benzopyran compound that was shown to prolong the atrial effective refractory period and terminate experimental atrial fibrillation in the dog. In the present study, we examined the effects of NIP-142 on isolated guinea pig myocardium and on the G-protein-coupled inwardly rectifying potassium channel current (acetylcholine-activated potassium current; I(KACh)) expressed in Xenopus oocytes. NIP-142 (10 and 100 microM) concentration-dependently prolonged the refractory period and action potential duration in the atrium but not in the ventricle. E-4031 and 4-aminopyridine prolonged action potential duration in both left atrium and right ventricle. Prolongation by NIP-142 of the atrial action potential duration was observed at stimulation frequencies between 0.5 and 5 Hz. In contrast, the prolongation by E-4031 was not observed at higher frequencies. Tertiapin, a blocker of I(KACh), prolonged action potential duration in the atrium but not in the ventricle. NIP-142 completely reversed the carbachol-induced shortening of atrial action potential duration. NIP-142 (1 to 100 microM), as well as tertiapin (0.1 to 100 nM), concentration-dependently blocked I(KACh) expressed in Xenopus oocytes; the blockade by NIP-142 was not affected by membrane voltage. In conclusion, NIP-142 was shown to prolong atrial refractory period and action potential duration through blockade of I(KACh) which may possibly explain its previously described antiarrhythmic activity. NIP-142 has pharmacological properties that are different from classical class III antiarrhythmic agents such as atria specificity and lack of reverse frequency dependence, and thus appears promising for the treatment of supraventricular arrhythmia.

  11. Resilient RTN fast spiking in Kv3.1 null mice suggests redundancy in the action potential repolarization mechanism.

    PubMed

    Porcello, Darrell M; Ho, Chi Shun; Joho, Rolf H; Huguenard, John R

    2002-03-01

    Fast spiking (FS), GABAergic neurons of the reticular thalamic nucleus (RTN) are capable of firing high-frequency trains of brief action potentials, with little adaptation. Studies in recombinant systems have shown that high-voltage-activated K(+) channels containing the Kv3.1 and/or Kv3.2 subunits display biophysical properties that may contribute to the FS phenotype. Given that RTN expresses high levels of Kv3.1, with little or no Kv3.2, we tested whether this subunit was required for the fast action potential repolarization mechanism essential to the FS phenotype. Single- and multiple-action potentials were recorded using whole-cell current clamp in RTN neurons from brain slices of wild-type and Kv3.1-deficient mice. At 23 degrees C, action potentials recorded from homozygous Kv3.1 deficient mice (Kv3.1(-/-)) compared with their wild-type (Kv3.1(+/+)) counterparts had reduced amplitudes (-6%) and fast after-hyperpolarizations (-16%). At 34 degrees C, action potentials in Kv3.1(-/-) mice had increased duration (21%) due to a reduced rate of repolarization (-30%) when compared with wild-type controls. Action potential trains in Kv3.1(-/-) were associated with a significantly greater spike decrement and broadening and a diminished firing frequency versus injected current relationship (F/I) at 34 degrees C. There was no change in either spike count or maximum instantaneous frequency during low-threshold Ca(2+) bursts in Kv3.1(-/-) RTN neurons at either temperature tested. Our findings show that Kv3.1 is not solely responsible for fast spikes or high-frequency firing in RTN neurons. This suggests genetic redundancy in the system, possibly in the form of other Kv3 members, which may suffice to maintain the FS phenotype in RTN neurons in the absence of Kv3.1.

  12. Analysis of acid-generating action of PAG in an EUV resist using acid-sensitive dyes

    NASA Astrophysics Data System (ADS)

    Sekiguchi, Atsushi; Matsumoto, Yoko; Biafore, John J.

    2013-03-01

    Researchers are currently examining various methods for determining the quantity of acid generated by a photoacid generator (PAG) and for analyzing acid-generating reactions using acid-sensitive dyes that react with acid and generate a color. Adding an acid-sensitive dye to the resist gives a clear grasp of the acid-generating action. The process involves applying a resist containing an acid-sensitive dye to a quartz substrate; exposing the substrate; and measuring and evaluating the absorbance of a chromogenic substance near 530 nm using a spectroscope. The method determines the rate constant for acid generation (Dill C parameter) during exposure based on the relationship between transmissivity at 530 nm and exposure dose. Using this method, we obtained and compared rate constants for acid generation (C parameters) as part of our study of dependence on the quantity of quencher in the EUV resist. Our results indicate a new model that accounts for the quencher concentration parameter would be useful in analyzing dependence on the quantity of quencher. This paper presents these findings, together with the results of studies of profile simulations using the quencher concentration parameter obtained in the experiments.

  13. 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.

  14. The mitochondrial monoamine oxidase-aldehyde dehydrogenase pathway: a potential site of action of daidzin.

    PubMed

    Rooke, N; Li, D J; Li, J; Keung, W M

    2000-11-02

    Recent studies showed that daidzin suppresses ethanol intake in ethanol-preferring laboratory animals. In vitro, it potently and selectively inhibits the mitochondrial aldehyde dehydrogenase (ALDH-2). Further, it inhibits the conversion of monoamines such as serotonin (5-HT) and dopamine (DA) into their respective acid metabolites, 5-hydroxyindole-3-acetic acid (5-HIAA) and 3,4-dihydroxyphenylacetic acid (DOPAC) in isolated hamster or rat liver mitochondria. Studies on the suppression of ethanol intake and inhibition of 5-HIAA (or DOPAC) formation by six structural analogues of daidzin suggested a potential link between these two activities. This, together with the finding that daidzin does not affect the rates of mitochondria-catalyzed oxidative deamination of these monoamines, raised the possibility that the ethanol intake-suppressive (antidipsotropic) action of daidzin is not mediated by the monoamines but rather by their reactive biogenic aldehyde intermediates such as 5-hydroxyindole-3-acetaldehyde (5-HIAL) and/or 3,4-dihydroxyphenylacetaldehyde (DOPAL) which accumulate in the presence of daidzin. To further evaluate this possibility, we synthesized more structural analogues of daidzin and tested and compared their antidipsotropic activities in Syrian golden hamsters with their effects on monoamine metabolism in isolated hamster liver mitochondria using 5-HT as the substrate. Effects of daidzin and its structural analogues on the activities of monoamine oxidase (MAO) and ALDH-2, the key enzymes involved in 5-HT metabolism in the mitochondria, were also examined. Results from these studies reveal a positive correlation between the antidipsotropic activities of these analogues and their abilities to increase 5-HIAL accumulation during 5-HT metabolism in isolated hamster liver mitochondria. Daidzin analogues that potently inhibit ALDH-2 but have no or little effect on MAO are most antidipsotropic, whereas those that also potently inhibit MAO exhibit little, if

  15. 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

  16. Atrial Heterogeneity Generates Re-entrant Substrate during Atrial Fibrillation and Anti-arrhythmic Drug Action: Mechanistic Insights from Canine Atrial Models

    PubMed Central

    Varela, Marta; Hancox, Jules C.; Aslanidi, Oleg V.

    2016-01-01

    Anti-arrhythmic drug therapy is a frontline treatment for atrial fibrillation (AF), but its success rates are highly variable. This is due to incomplete understanding of the mechanisms of action of specific drugs on the atrial substrate at different stages of AF progression. We aimed to elucidate the role of cellular, tissue and organ level atrial heterogeneities in the generation of a re-entrant substrate during AF progression, and their modulation by the acute action of selected anti-arrhythmic drugs. To explore the complex cell-to-organ mechanisms, a detailed biophysical models of the entire 3D canine atria was developed. The model incorporated atrial geometry and fibre orientation from high-resolution micro-computed tomography, region-specific atrial cell electrophysiology and the effects of progressive AF-induced remodelling. The actions of multi-channel class III anti-arrhythmic agents vernakalant and amiodarone were introduced in the model by inhibiting appropriate ionic channel currents according to experimentally reported concentration-response relationships. AF was initiated by applied ectopic pacing in the pulmonary veins, which led to the generation of localized sustained re-entrant waves (rotors), followed by progressive wave breakdown and rotor multiplication in both atria. The simulated AF scenarios were in agreement with observations in canine models and patients. The 3D atrial simulations revealed that a re-entrant substrate was typically provided by tissue regions of high heterogeneity of action potential duration (APD). Amiodarone increased atrial APD and reduced APD heterogeneity and was more effective in terminating AF than vernakalant, which increased both APD and APD dispersion. In summary, the initiation and sustenance of rotors in AF is linked to atrial APD heterogeneity and APD reduction due to progressive remodelling. Our results suggest that anti-arrhythmic strategies that increase atrial APD without increasing its dispersion are

  17. 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.…

  18. Potential Applications for Nuclear Energy besides Electricity Generation: AREVA Global Perspective of HTR Potential Market

    SciTech Connect

    Soutworth, Finis; Gauthier, Jean-Claude; Lecomte, Michel; Carre, Franck

    2007-07-01

    Energy supply is increasingly showing up as a major issue for electricity supply, transportation, settlement, and process heat industrial supply including hydrogen production. Nuclear power is part of the solution. For electricity supply, as exemplified in Finland and France, the EPR brings an immediate answer; HTR could bring another solution in some specific cases. For other supply, mostly heat, the HTR brings a solution inaccessible to conventional nuclear power plants for very high or even high temperature. As fossil fuels costs increase and efforts to avoid generation of Greenhouse gases are implemented, a market for nuclear generated process heat will develop. Following active developments in the 80's, HTR have been put on the back burner up to 5 years ago. Light water reactors are widely dominating the nuclear production field today. However, interest in the HTR technology was renewed in the past few years. Several commercial projects are actively promoted, most of them aiming at electricity production. ANTARES is today AREVA's response to the cogeneration market. It distinguishes itself from other concepts with its indirect cycle design powering a combined cycle power plant. Several reasons support this design choice, one of the most important of which is the design flexibility to adapt readily to combined heat and power applications. From the start, AREVA made the choice of such flexibility with the belief that the HTR market is not so much in competition with LWR in the sole electricity market but in the specific added value market of cogeneration and process heat. In view of the volatility of the costs of fossil fuels, AREVA's choice brings to the large industrial heat applications the fuel cost predictability of nuclear fuel with the efficiency of a high temperature heat source free of greenhouse gases emissions. The ANTARES module produces 600 MWth which can be split into the required process heat, the remaining power drives an adapted prorated

  19. Clarithromycin reduces Isus and Ito currents in human atrial myocytes with minor repercussions on action potential duration.

    PubMed

    Gluais, Pascale; Bastide, Michèle; Grandmougin, Daniel; Fayad, Georges; Adamantidis, Monique

    2003-12-01

    The macrolide antibacterial agent clarithromycin has been shown to cause QT interval prolongation on the electrocardiogram. In rabbit heart preparations clarithromycin (concentration dependently) lengthened the action potential duration and blocked the delayed rectifier current. The aim of the present study was to investigate the clarithromycin effects: (i) on the Ca2+ L-type and the main K+ repolarizing currents on human atrial myocytes, using whole-cell patch clamp recordings and (ii) on action potentials recorded from human atrial and ventricular myocardium using conventional microelectrodes. It has been found that (i) 10-30 microM clarithromycin reduced the sustained current Isus significantly and that a 100 microM concentration was needed to cause a significant reduction in the transient outward current Ito, whereas clarithomycin did not affect the calcium current and (ii) clarithromycin (10-100 microM) prolonged the action potential duration in atrial preparations but did not alter the different parameters of the ventricular action potential. It is concluded that clarithromycin exerts direct cardiac electrophysiological effects that may contribute to pro-arrythmic potential.

  20. Pre- and postnatal differences in membrane, action potential, and ion channel properties of rostral nucleus of the solitary tract neurons

    PubMed Central

    Suwabe, Takeshi; Mistretta, Charlotte M.; Krull, Catherine

    2011-01-01

    There is little known about the prenatal development of the rostral nucleus of the solitary tract (rNST) neurons in rodents or the factors that influence circuit formation. With morphological and electrophysiological techniques in vitro, we investigated differences in the biophysical properties of rNST neurons in pre- and postnatal rats from embryonic day 14 (E14) through postnatal day 20. Developmental changes in passive membrane and action potential (AP) properties and the emergence and maturation of ion channels important in neuron function were characterized. Morphological maturation of rNST neurons parallels changes in passive membrane properties. Mean soma size, dendritic branch points, neurite endings, and neurite length all increase prenatally. whereas neuron resting membrane potential, input resistance, and time constant decrease. Dendritic spines, on the other hand, develop after birth. AP discharge patterns alter in pre- and postnatal stages. At E14, neurons generated a single TTX-sensitive, voltage-gated Na+ AP when depolarized; a higher discharge rate appeared at older stages. AP amplitude, half-width, and rise and fall times all change during development. Responses to current injection revealed a number of voltage-gated conductances in embryonic rNST, including a hyperpolarization-activated inward current and a low-threshold Ca2+ current that initiated Ca2+ spikes. A hyperpolarization-activated, transient outward potassium current was also present in the developing neurons. Although the properties of these channels change during development, they are present before synapses form and therefore, can contribute to initial establishment of neural circuits, as well as to the changing electrophysiological properties in developing rNST neurons. PMID:21865434

  1. Blockade of sensory neuron action potentials by a static magnetic field in the 10 mT range

    SciTech Connect

    McLean, M.J.; Holcomb, R.R.; Wamil, A.W.; Pickett, J.D.; Cavopol, A.V.

    1995-05-01

    To characterize the inhibitory effect of a static magnetic field, action potentials (AP) were elicited by intracellular application of 1 ms depolarizing current pulses of constant amplitude to the somata of adult mouse dorsal root ganglion neurons in monolayer dissociated cell culture. During the control period, < 5% of stimuli failed to elicit AP. During exposure to an {approximately}11 mT static magnetic field at the cell position produced by an array of four permanent center-charged neodymium magnets of alternating polarity (MAG-4A), 66% of stimuli failed to elicit AP. The number of failures was maximal after about 200--250 s in the field and returned gradually to baseline over 400--600 s. A direct or indirect effect on the conformation of AP generating sodium channels could account for these results because (1) failure was preceded often by reduction of maximal rate of rise, an indirect measure of sodium current; (2) recovery was significantly prolonged in more than one-half of neurons that were not stimulated during exposure to the MAG-4A field; and (3) resting membrane potential, input resistance, and chronaxie were unaffected by the field. The effect was diminished or prevented by moving the MAG-4A array along the X or Z axis away from the neuron under study and by increasing the distance between magnets in the XY plane. Reduction of AP firing during exposure to the {approximately}0.1 mT field produced by a MAG-4A array of micromagnets was about the same as that produced by a MAG-4A array of the large magnets above. The {approximately}28 mT field produced at cell position by two magnets of alternating polarity and the {approximately}88 mT field produced by a single magnet had no significant effect on AP firing. These findings suggest that field strength alone cannot account for AP blockade.

  2. The macaque lateral grasping network: A neural substrate for generating purposeful hand actions.

    PubMed

    Borra, Elena; Gerbella, Marzio; Rozzi, Stefano; Luppino, Giuseppe

    2017-04-01

    In primates, neural mechanisms for controlling skilled hand actions primarily rely on sensorimotor transformations. These transformations are mediated by circuits linking specific inferior parietal with ventral premotor areas in which sensory coding of objects' features automatically triggers appropriate hand motor programs. Recently, connectional studies in macaques showed that these parietal and premotor areas are nodes of a large-scale cortical network, designated as "lateral grasping network," including specific temporal and prefrontal sectors involved in object recognition and executive functions, respectively. These data extend grasping models so far proposed in providing a possible substrate for interfacing perceptual, cognitive, and hand-related sensorimotor processes for controlling hand actions based on object identity, goals, and memory-based or contextual information and for the contribution of motor signals to cognitive motor functions. Human studies provided evidence for a possible counterpart of the macaque lateral grasping network, suggesting that in primate evolution the neural mechanisms for controlling hand actions described in the macaque have been retained and exploited for the emergence of human-specific motor and cognitive motor capacities.

  3. Linear and nonlinear Biot waves in a noncohesive granular medium slab: transfer function, self-action, second harmonic generation.

    PubMed

    Legland, J-B; Tournat, V; Dazel, O; Novak, A; Gusev, V

    2012-06-01

    Experimental results are reported on second harmonic generation and self-action in a noncohesive granular medium supporting wave energy propagation both in the solid frame and in the saturating fluid. The acoustic transfer function of the probed granular slab can be separated into two main frequency regions: a low frequency region where the wave propagation is controlled by the solid skeleton elastic properties, and a higher frequency region where the behavior is dominantly due to the air saturating the beads. Experimental results agree well with a recently developed nonlinear Biot wave model applied to granular media. The linear transfer function, second harmonic generation, and self-action effect are studied as a function of bead diameter, compaction step, excitation amplitude, and frequency. This parametric study allows one to isolate different propagation regimes involving a range of described and interpreted linear and nonlinear processes that are encountered in granular media experiments. In particular, a theoretical interpretation is proposed for the observed strong self-action effect.

  4. Spatial variation of compound muscle action potentials across human gastrocnemius medialis

    PubMed Central

    Vieira, Taian M.; Minetto, Marco A.; Hodson-Tole, Emma F.

    2015-01-01

    The massed action potential (M wave) elicited through nerve stimulation underpins a wide range of physiological and mechanical understanding of skeletal muscle structure and function. Although systematic approaches have evaluated the effect of different factors on M waves, the effect of the location and distribution of activated fibers within the muscle remains unknown. By detecting M waves from the medial gastrocnemius (MG) of 12 participants with a grid of 128 electrodes, we investigated whether different populations of muscle units have different spatial organization within MG. If populations of muscle units occupy discrete MG regions, current pulses of progressively greater intensities applied to the MG nerve branch would be expected to lead to local changes in M-wave amplitudes. Electrical pulses were therefore delivered at 2 pps, with the current pulse amplitude increased every 10 stimuli to elicit different degrees of muscle activation. The localization of MG response to increases in current intensity was determined from the spatial distribution of M-wave amplitude. Key results revealed that increases in M-wave amplitude were detected somewhat locally, by 10–50% of the 128 electrodes. Most importantly, the electrodes detecting greatest increases in M-wave amplitude were localized at different regions in the grid, with a tendency for greater stimulation intensities to elicit M waves in the more distal MG region. The presented results indicate that M waves recorded locally may not provide a representative MG response, with major implications for the estimation of, e.g., the maximal stimulation levels, the number of motor units, and the onset and normalization in H-reflex studies. PMID:26156382

  5. The Mechanisms of Calcium Cycling and Action Potential Dynamics in Cardiac Alternans

    PubMed Central

    Kanaporis, Giedrius; Blatter, Lothar A.

    2015-01-01

    Rationale Alternans is a risk factor for cardiac arrhythmia, including atrial fibrillation. At the cellular level alternans manifests as beat-to-beat alternations in contraction, action potential duration (APD) and magnitude of the Ca2+ transient (CaT). Electromechanical and CaT alternans are highly correlated, however it has remained controversial whether the primary cause of alternans is a disturbance of cellular Ca2+ signaling or electrical membrane properties. Objective Determine whether a primary failure of intracellular Ca2+ regulation or disturbances in Vm and AP regulation are responsible for the occurrence of alternans in atrial myocytes. Methods and Results Pacing-induced APD and CaT alternans were studied in single rabbit atrial and ventricular myocytes using combined [Ca2+]i and electrophysiological measurements. In current-clamp experiments APD and CaT alternans strongly correlated in time and magnitude. CaT alternans was observed without alternation in L-type Ca2+ current, however, elimination of intracellular Ca2+ release abolished APD alternans, indicating that [Ca2+]i dynamics have a profound effect on the occurrence of CaT alternans. Trains of two distinctive voltage commands in form of APs recorded during large and small alternans CaTs, were applied to voltage-clamped cells. CaT alternans were observed with and without alternation in the voltage command shape. During ‘alternans AP-clamp’ large CaTs coincided with both long and short AP waveforms, indicating that CaT alternans develop irrespective of AP dynamics. Conclusion The primary mechanism underlying alternans in atrial cells, similarly to ventricular cells, resides in a disturbance of Ca2+ signaling while APD alternans are a secondary consequence, mediated by Ca2+-dependent AP modulation. PMID:25532796

  6. Action potential bursts enhance transmitter release at a giant central synapse.

    PubMed

    Zhang, Bo; Sun, Liang; Yang, Yi-Mei; Huang, Hong-Ping; Zhu, Fei-Peng; Wang, Li; Zhang, Xiao-Yu; Guo, Shu; Zuo, Pan-Li; Zhang, Claire X; Ding, Jiu-Ping; Wang, Lu-Yang; Zhou, Zhuan

    2011-05-01

    Patterns of action potentials (APs), often in the form of bursts, are critical for coding and processing information in the brain. However, how AP bursts modulate secretion at synapses remains elusive. Here, using the calyx of Held synapse as a model we compared synaptic release evoked by AP patterns with a different number of bursts while the total number of APs and frequency were fixed. The ratio of total release produced by multiple bursts to that by a single burst was defined as 'burst-effect'.We found that four bursts of 25 stimuli at 100 Hz increased the totalcharge of EPSCs to 1.47 ± 0.04 times that by a single burst of 100 stimuli at the same frequency.Blocking AMPA receptor desensitization and saturation did not alter the burst-effect, indicating that it was mainly determined by presynaptic mechanisms. Simultaneous dual recordings of presynaptic membrane capacitance (Cm) and EPSCs revealed a similar burst-effect, being 1.58±0.13by Cm and 1.49±0.05 by EPSCs. Reducing presynapticCa2+ influx by lowering extracellular Ca2+concentration or buffering residual intracellular Ca2+ with EGTA inhibited the burst-effect. We further developed a computational model largely recapitulating the burst-effect and demonstrated that this effect is highly sensitive to dynamic change in availability of the releasable pool of synaptic vesicles during various patterns of activities. Taken together, we conclude that AP bursts modulate synaptic output mainly through intricate interaction between depletion and replenishment of the large releasable pool. This burst-effect differs from the somatic burst-effect previously described from adrenal chromaffin cells, which substantially depends on activity-induced accumulation of Ca2+ to facilitate release of a limited number of vesicles in the releasable pool. Hence, AP bursts may play an important role in dynamically regulating synaptic strength and fidelity during intense neuronal activity at central synapses.

  7. 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

  8. 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

  9. The role of action potentials in determining neuron-type-specific responses to nitric oxide.

    PubMed

    Estes, Stephen; Zhong, Lei Ray; Artinian, Liana; Tornieri, Karine; Rehder, Vincent

    2015-05-01

    The electrical activity in developing and mature neurons determines the intracellular calcium concentration ([Ca(2+)]i), which in turn is translated into biochemical activities through various signaling cascades. Electrical activity is under control of neuromodulators, which can alter neuronal responses to incoming signals and increase the fidelity of neuronal communication. Conversely, the effects of neuromodulators can depend on the ongoing electrical activity within target neurons; however, these activity-dependent effects of neuromodulators are less well understood. Here, we present evidence that the neuronal firing frequency and intrinsic properties of the action potential (AP) waveform set the [Ca(2+)]i in growth cones and determine how neurons respond to the neuromodulator nitric oxide (NO). We used two well-characterized neurons from the freshwater snail Helisoma trivolvis that show different growth cone morphological responses to NO: B5 neurons elongate filopodia, while those of B19 neurons do not. Combining whole-cell patch clamp recordings with simultaneous calcium imaging, we show that the duration of an AP contributes to neuron-specific differences in [Ca(2+)]i, with shorter APs in B19 neurons yielding lower growth cone [Ca(2+)]i. Through the partial inhibition of voltage-gated K(+) channels, we increased the B19 AP duration resulting in a significant increase in [Ca(2+)]i that was then sufficient to cause filopodial elongation following NO treatment. Our results demonstrate a neuron-type specific correlation between AP shape, [Ca(2+)]i, and growth cone motility, providing an explanation to how growth cone responses to guidance cues depend on intrinsic electrical properties and helping explain the diverse effects of NO across neuronal populations.

  10. Intact Heart Loose Patch Photolysis Reveals Ionic Current Kinetics During Ventricular Action Potentials

    PubMed Central

    Ramos-Franco, Josefina; Aguilar-Sanchez, Yuriana; Escobar, Ariel L.

    2016-01-01

    Rationale Assessing the underlying ionic currents during a triggered action potential (AP) in intact perfused hearts offers the opportunity to link molecular mechanisms with pathophysiological problems in cardiovascular research. The developed Loose Patch Photolysis (LPP) technique can provide striking new insights into cardiac function at the whole heart level during health and disease. Objective To measure transmembrane ionic currents during an AP in order to determine how and when surface Ca2+ influx that triggers Ca2+ induced Ca2+ release (CICR) occurs and how Ca2+ activated conductances can contribute to the genesis of AP phase 2. Methods and Results LPP allows the measurement of transmembrane ionic currents in intact hearts. During a triggered AP, a voltage-dependent Ca2+ conductance was fractionally activated (dis-inhibited) by rapidly photo-degrading nifedipine, the Ca2+ channel blocker. The ionic currents during a mouse ventricular AP showed a fast early component and a slower late component. Pharmacological studies established that the molecular basis underlying the early component was driven by an influx of Ca2+ through the L-type channel, CaV 1.2. The late component was identified as a Na+-Ca2+ exchanger (NCX) current mediated by Ca2+ released from the sarcoplasmic reticulum (SR). Conclusions The novel LPP technique allowed the dissection of transmembrane ionic currents in the intact heart. We were able to determine that during an AP L-Type Ca2+ current contributes to phase 1 while NCX contributes to phase 2. In addition, LPP revealed that the influx of Ca2+ through L-type Ca2+ channels terminates due to voltage-dependent deactivation and not by Ca2+ dependent inactivation, as commonly believed. PMID:26565013

  11. Automatic analysis of auditory nerve electrically evoked compound action potential with an artificial neural network.

    PubMed

    Charasse, Basile; Thai-Van, Hung; Chanal, Jean Marc; Berger-Vachon, Christian; Collet, Lionel

    2004-07-01

    The auditory nerve's electrically evoked compound action potential is recorded in deaf patients equipped with the Nucleus 24 cochlear implant using a reverse telemetry system (NRT). Since the threshold of the NRT response (NRT-T) is thought to reflect the psychophysics needed for programming cochlear implants, efforts have been made by specialized management teams to develop its use. This study aimed at developing a valid tool, based on artificial neural networks (ANN) technology, for automatic estimation of NRT-T. The ANN used was a single layer perceptron, trained with 120 NRT traces. Learning traces differed from data used for the validation. A total of 550 NRT traces from 11 cochlear implant subjects were analyzed separately by the system and by a group of physicians with expertise in NRT analysis. Both worked to determine 37 NRT-T values, using the response amplitude growth function (AGF) (linear regression of response amplitudes obtained at decreasing stimulus intensity levels). The validity of the system was assessed by comparing the NRT-T values automatically determined by the system with those determined by the physicians. A strong correlation was found between automatic and physician-obtained NRT-T values (Pearson r correlation coefficient >0.9). ANOVA statistics confirmed that automatic NRT-Ts did not differ from physician-obtained values (F = 0.08999, P = 0.03). Moreover, the average error between NRT-Ts predicted by the system and NRT-Ts measured by the physicians (3.6 stimulation units) did not differ significantly from the average error between NRT-Ts measured by each of the three physicians (4.2 stimulation units). In conclusion, the automatic system developed in this study was found to be as efficient as human experts for fitting the amplitude growth function and estimating NRT-T, with the advantage of considerable time-saving.

  12. Developmental impairment of compound action potential in the optic nerve of myelin mutant taiep rats.

    PubMed

    Roncagliolo, Manuel; Schlageter, Carol; León, Claudia; Couve, Eduardo; Bonansco, Christian; Eguibar, José R

    2006-01-05

    The taiep rat is a myelin mutant with an initial hypomyelination, followed by a progressive demyelination of the CNS. The neurological correlates start with tremor, followed by ataxia, immobility episodes, epilepsy and paralysis. The optic nerve, an easily-isolable central tract fully myelinated by oligodendrocytes, is a suitable preparation to evaluate the developmental impairment of central myelin. We examined the ontogenic development of optic nerve compound action potentials (CAP) throughout the first 6 months of life of control and taiep rats. Control optic nerves (ON) develop CAPs characterized by three waves. Along the first month, the CAPs of taiep rats showed a delayed maturation, with lower amplitudes and longer latencies than controls; at P30, the conduction velocity has only a third of the normal value. Later, as demyelination proceeds, the conduction velocity of taiep ONs begins to decrease and CAPs undergo a gradual temporal dispersion. CAPs of control and taiep showed differences in their pharmacological sensitivity to TEA and 4-AP, two voltage dependent K+ channel-blockers. As compared with TEA, 4-AP induced a significant increase of the amplitudes and a remarkable broadening of CAPs. After P20, unlike controls, the greater sensitivity to 4-AP exhibited by taiep ONs correlates with the detachment and retraction of paranodal loops suggesting that potassium conductances could regulate the excitability as demyelination of CNS axons progresses. It is concluded that the taiep rat, a long-lived mutant, provides a useful model to study the consequences of partial demyelination and the mechanisms by which glial cells regulate the molecular organization and excitability of axonal membranes during development and disease.

  13. Biphasic cholinergic synaptic transmission controls action potential activity in thalamic reticular nucleus neurons.

    PubMed

    Sun, Yan-Gang; Pita-Almenar, Juan D; Wu, Chia-Shan; Renger, John J; Uebele, Victor N; Lu, Hui-Chen; Beierlein, Michael

    2013-01-30

    Cholinergic neurons in the basal forebrain and the brainstem form extensive projections to a number of thalamic nuclei. Activation of cholinergic afferents during distinct behavioral states can regulate neuronal firing, transmitter release at glutamatergic and GABAergic synapses, and synchrony in thalamic networks, thereby controlling the flow of sensory information. These effects are thought to be mediated by slow and persistent increases in extracellular ACh levels, resulting in the modulation of populations of thalamic neurons over large temporal and spatial scales. However, the synaptic mechanisms underlying cholinergic signaling in the thalamus are not well understood. Here, we demonstrate highly reliable cholinergic transmission in the mouse thalamic reticular nucleus (TRN), a brain structure essential for sensory processing, arousal, and attention. We find that ACh release evoked by low-frequency stimulation leads to biphasic excitatory-inhibitory (E-I) postsynaptic responses, mediated by the activation of postsynaptic α4β2 nicotinic ACh receptors (nAChRs) and M2 muscarinic ACh receptors (mAChRs), respectively. In addition, ACh can bind to mAChRs expressed near cholinergic release sites, resulting in autoinhibition of release. We show that the activation of postsynaptic nAChRs by transmitter release from only a small number of individual axons is sufficient to trigger action potentials in TRN neurons. Furthermore, short trains of cholinergic synaptic inputs can powerfully entrain ongoing TRN neuronal activity. Our study demonstrates fast and precise synaptic E-I signaling mediated by ACh, suggesting novel computational mechanisms for the cholinergic control of neuronal activity in thalamic circuits.

  14. Beta-adrenergic stimulation reverses the IKr–IKs dominant pattern during cardiac action potential

    PubMed Central

    Banyasz, Tamas; Jian, Zhong; Horvath, Balazs; Khabbaz, Shaden; Izu, Leighton T.; Chen-Izu, Ye

    2014-01-01

    β-adrenergic stimulation differentially modulates different K+ channels and thus fine-tunes cardiac action potential (AP) repolarization. However, it remains unclear how the proportion of IKs, IKr, and IK1 current in the same cell would be altered by β-adrenergic stimulation, which would change the relative contribution of individual K+ current to the total repolarization reserve. In this study we used an innovative AP-clamp Sequential Dissection technique to directly record the dynamic –IKs, IKr, IK1– currents during the AP in guinea pig ventricular myocytes under physiologically relevant conditions. Our data provide quantitative measures of the magnitude and time course of IKs, IKr, IK1 currents in the same cell under its own steady-state AP, in a physiological milieu, and with preserved Ca2+ homeostasis. We found that isoproterenol treatment significantly enhanced IKs, moderately increased IK1, but slightly decreased IKr in a dose-dependent manner. The dominance pattern of the K+ currents was IKr>IK1>IKs at the control condition, but reversed to IKr

  15. Action