Science.gov

Sample records for action potential discharge

  1. 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.

  2. Action potential in charophytes.

    PubMed

    Beilby, Mary Jane

    2007-01-01

    The plant action potential (AP) has been studied for more than half a century. The experimental system was provided mainly by the large charophyte cells, which allowed insertion of early large electrodes, manipulation of cell compartments, and inside and outside media. These early experiments were inspired by the Hodgkin and Huxley (HH) work on the squid axon and its voltage clamp techniques. Later, the patch clamping technique provided information about the ion transporters underlying the excitation transient. The initial models were also influenced by the HH picture of the animal AP. At the turn of the century, the paradigm of the charophyte AP shifted to include several chemical reactions, second messenger-activated channel, and calcium ion liberation from internal stores. Many aspects of this new model await further clarification. The role of the AP in plant movements, wound signaling, and turgor regulation is now well documented. Involvement in invasion by pathogens, chilling injury, light, and gravity sensing are under investigation.

  3. Corrective Action Decision Document for Corrective Action Unit 516: Septic Systems and Discharge Points, Nevada Test Site, Nevada: Revision 1

    SciTech Connect

    U.S. Department of Energy, National Nuclear Security Administration Nevada Site Office

    2004-04-28

    This Corrective Action Decision Document (CADD) identifies and rationalizes the U.S. Department of Energy, National Nuclear Security Administration Nevada Site Office's selection of a recommended corrective action alternative appropriate to facilitate the closure of Corrective Action Unit (CAU) 516: Septic Systems and Discharge Points, Nevada Test Site (NTS), Nevada, under the Federal Facility Agreement and Consent Order. Located in Areas 3, 6, and 22 on the NTS, CAU 516 includes six Corrective Action Sites (CASs) consisting of two septic systems, a sump and piping, a clean-out box and piping, dry wells, and a vehicle decontamination area. Corrective action investigation activities were performed from July 22 through August 14, 2003, with supplemental sampling conducted in late 2003 and early 2004. The potential exposure pathways for any contaminants of concern (COCs) identified during the development of the DQOs at CAU 516 gave rise to the following objectives: (1) prevent or mitigate exposure to media containing COCs at concentrations exceeding PALs as defined in the corrective action investigation plan; and (2) prevent the spread of COCs beyond each CAS. The following alternatives have been developed for consideration at CAU 516: Alternative 1 - No Further Action; Alternative 2 - Clean Closure; and Alternative 3 - Closure in Place with Administrative Controls. Alternative 1, No Further Action, is the preferred corrective action for two CASs (06-51-02 and 22-19-04). Alternative 2, Clean Closure, is the preferred corrective action for four CASs (03-59-01, 03-59-02, 06-51-01, and 06-51-03). The selected alternatives were judged to meet all requirements for the technical components evaluated, as well as meeting all applicable state and federal regulations for closure of the site and will further eliminate the contaminated media at CAU 516.

  4. Characteristics of cardiac action potentials in marsupials.

    PubMed

    Campbell, T J

    1989-01-01

    Standard microelectrode techniques were used to record action potentials from single atrial, ventricular and Purkinje fibers of hearts taken from three species of marsupial (Macropus rufus, Macropus robustus and Macropus eugenii) and from dogs, sheep and guinea-pigs. The major electrophysiological parameters of marsupial potentials were qualitatively similar to the values for placental mammals. The grouped data for ventricular action potentials from studies on 6 adult male red kangaroos (Macropus rufus) were (mean +/- SD): Resting potential -69.5 +/- 5.0 mV; action potential amplitude 92.7 +/- 5.7 mV; action potential duration (to 90% repolarization): 182.5 +/- 17.5 ms; maximum rate of depolarization: 196.5 +/- 80.1 V/s. The major point of difference was the short duration of the red kangaroo ventricular action potential compared to those of the placental mammals, and compared to atrial cells from the kangaroos. It is suggested that this explains the short QT interval reported by others for kangaroo electrocardiograms, and that it may also be implicated in the high frequency of sudden death previously noted in these animals.

  5. Antimicrobial action of a discharge with a liquid cathode on the electrode liquid

    NASA Astrophysics Data System (ADS)

    Barinov, Yu. A.; Kuzikova, I. L.; Zinov'eva, S. V.; Shkol'nik, S. M.; Medvedeva, N. G.

    2015-09-01

    The antimicrobial influence of a discharge with a liquid cathode on an electrode liquid at atmospheric pressure was studied. The degree of the antimicrobial action of the discharge was shown to depend on the treatment regime and on the species of investigated microorganism test cultures. Gram-negative bacteria Pseudomonas fluorescens show the most prominent sensitivity to the treatment. Yeastlike fungi Candida albicans and gram-positive bacteria Bacillus subtilis are more resistant toward the action of the discharge. Increasing the duration of the treatment and raising the current from 60 to 150 mA leads to an increase in the inhibiting action on cells of P. fluorescens and C. albicans.

  6. Corrective Action Plan for Corrective Action Unit 151: Septic Systems and Discharge Area, Nevada Test Site, Nevada

    SciTech Connect

    NSTec Environmental Restoration

    2007-03-01

    Corrective Action Unit (CAU) 151, Septic Systems and Discharge Area, is listed in the Federal Facility Agreement and Consent Order (FFACO) of 1996 (FFACO, 1996). CAU 151 consists of eight Corrective Action Sites (CASs) located in Areas 2, 12, and 18 of the Nevada Test Site (NTS), which is located approximately 65 miles northwest of Las Vegas, Nevada.

  7. CORRECTIVE ACTION DECISION DOCUMENT FOR CORRECTIVE ACTION UNIT 423: BUILDING 03-60 UNDERGROUND DISCHARGE POINT, TONOPAH TEST RANGE, NEVADA, REVISION 0, JUNE 1998

    SciTech Connect

    1998-06-01

    This Corrective Action Decision Document has been prepared for the Area 3 Building 03-60 Underground Discharge Point (Corrective Action Unit 423) in accordance with the Federal Facility Agreement and Consent Order of 1996 (FFACO, 1996). Corrective Action Unit 423 is located at the Tonopah Test Range and is comprised of Corrective Action Site 03-02-002-0308. The purpose of this Corrective Action Decision Document is to identify and provide a rationale for the selection of a recommended corrective action alternative for Corrective Action Unit 423. The scope of this Correction Action Decision Document consists of the following: � Develop corrective action objectives. � Identify corrective action alternative screening criteria. � Develop corrective action alternatives. � Perform detailed and comparative evaluations of the corrective action alternatives in relation to the corrective action objectives and screening criteria. � Recommend and justify a preferred corrective action alternative for the Corrective Action Unit. In January 1998, a corrective action investigation was performed as set forth in the Corrective Action Investigation Plan for Corrective Action Unit No. 423: Building 03-60 Underground Discharge Point, Tonopah Test Range, Nevada (DOE/NV, 1997). A hydrocarbon plume was found to emanate from near the bottom of the Underground Discharge Point to the west. The plume encompasses approximately 65 square meters (700 square feet). The highest total petroleum hydrocarbon level detected was 2,400 milligrams per kilogram. No other contaminants were detected above preliminary action levels. Details of the investigation can be found in Appendix A of this document. Based on the potential exposure pathways identified during the Data Quality Objectives process, the following corrective action objectives have been identified for Corrective Action Unit 423: � Prevent or mitigate human exposure to subsurface soil containing contaminants of concern. � Prevent

  8. 40 CFR 230.72 - Actions controlling the material after discharge.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 25 2014-07-01 2014-07-01 false Actions controlling the material after discharge. 230.72 Section 230.72 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) OCEAN... discharge to minimize impact, for instance during periods of unusual high water flows, wind, wave, and...

  9. 40 CFR 230.72 - Actions controlling the material after discharge.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 26 2012-07-01 2011-07-01 true Actions controlling the material after discharge. 230.72 Section 230.72 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) OCEAN... discharge to minimize impact, for instance during periods of unusual high water flows, wind, wave, and...

  10. 40 CFR 230.72 - Actions controlling the material after discharge.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 24 2010-07-01 2010-07-01 false Actions controlling the material after discharge. 230.72 Section 230.72 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) OCEAN... discharge to minimize impact, for instance during periods of unusual high water flows, wind, wave, and...

  11. 40 CFR 230.72 - Actions controlling the material after discharge.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 26 2013-07-01 2013-07-01 false Actions controlling the material after discharge. 230.72 Section 230.72 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) OCEAN... discharge to minimize impact, for instance during periods of unusual high water flows, wind, wave, and...

  12. Action of plasma jets of a low-current spark discharge on microorganisms ( Escherichia coli)

    NASA Astrophysics Data System (ADS)

    Baldanov, B. B.; Semenov, A. P.; Ranzhurov, Ts. V.; Nikolaev, E. O.; Gomboeva, S. V.

    2015-11-01

    High efficiency of bactericide action of cold argon plasma generated by plasma jets of a weak-current spark discharge under atmospheric pressure is demonstrated. It is found that an increase in the time of treatment with plasma jets from a low-current spark discharge makes it possible to effectively inactivate microorganisms over a much larger area.

  13. Correlation of action potentials in adjacent neurons

    NASA Astrophysics Data System (ADS)

    Shneider, M. N.; Pekker, M.

    2015-12-01

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

  14. Screening Action Potentials: The Power of Light

    PubMed Central

    Kaestner, Lars; Lipp, Peter

    2011-01-01

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

  15. 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…

  16. Laser action in runaway electron pre-ionized diffuse discharges

    NASA Astrophysics Data System (ADS)

    Panchenko, Alexei N.; Lomaev, Mikhail I.; Panchenko, Nikolai A.; Tarasenko, Viktor F.; Suslov, Alexei I.

    2015-12-01

    Formation features of run-away electron preionized diffuse discharge (REP DD) and REP DD properties in different experimental conditions are studied. It was shown that sufficient uniformity of REP DD allows its application as an excitation source of lasers on different gas mixtures at elevated pressure. Promising results of REP DD application for development of gas lasers are shown. Stimulated radiation in the IR, visible and UV spectral ranges was obtained in the diffuse discharge. Ultimate efficiency of non-chain HF(DF) chemical and nitrogen lasers on mixtures of SF6 with H2(D2) and N2 was achieved. New operation mode of nitrogen laser is demonstrated under REP DD excitation. Kinetic model of the REP DD in mixtures of nitrogen with SF6 is developed allowing to predict the radiation parameters of nitrogen laser at λ = 337,1 nm. Long-pulse operation of rare gas halide lasers was achieved.

  17. Potential Fluctuations and Energetic Ion Production in Hollow Cathode Discharges

    NASA Technical Reports Server (NTRS)

    Goebel, Dan M.; Jameson, Kristina K.; Katz, Ira; Mikellides, Ioannis G.

    2007-01-01

    Ions with energies significantly in excess of the applied discharge voltage have been reported for many years in hollow cathode discharges. Models of dc potential hills downstream of the cathode and instabilities in postulated double layers in the cathode orifice have been proposed to explain this, but have not been substantiated. Measurements of the dc and rf plasma density and potential profiles near the exit of hollow cathodes by miniature fast-scanning probes suggests that turbulent ion acoustic fluctuations and ionization instabilities in the cathode plume significantly increase the energy of the ions that flow from this region. Increases in the discharge current and/or decreases in the cathode gas flow enhance the amplitude of the fluctuations and increase the number and energy of the energetic ions, which increases the erosion rate of the cathode electrodes. The transition from the quiescent 'spot mode' to the noisy 'plume mode' characteristic of these discharges is found to be a gradual transition of increasing fluctuation amplitudes.

  18. 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

  19. 40 CFR 230.70 - Actions concerning the location of the discharge.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 25 2011-07-01 2011-07-01 false Actions concerning the location of the discharge. 230.70 Section 230.70 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) OCEAN DUMPING SECTION 404(b)(1) GUIDELINES FOR SPECIFICATION OF DISPOSAL SITES FOR DREDGED OR FILL MATERIAL Actions To Minimize Adverse Effects...

  20. 40 CFR 230.70 - Actions concerning the location of the discharge.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 26 2013-07-01 2013-07-01 false Actions concerning the location of the discharge. 230.70 Section 230.70 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) OCEAN DUMPING SECTION 404(b)(1) GUIDELINES FOR SPECIFICATION OF DISPOSAL SITES FOR DREDGED OR FILL MATERIAL Actions To Minimize Adverse Effects...

  1. 40 CFR 230.70 - Actions concerning the location of the discharge.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 26 2012-07-01 2011-07-01 true Actions concerning the location of the discharge. 230.70 Section 230.70 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) OCEAN DUMPING SECTION 404(b)(1) GUIDELINES FOR SPECIFICATION OF DISPOSAL SITES FOR DREDGED OR FILL MATERIAL Actions To Minimize Adverse Effects...

  2. Mechanical surface waves accompany action potential propagation.

    PubMed

    El Hady, Ahmed; Machta, Benjamin B

    2015-01-01

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

  3. Mechanical surface waves accompany action potential propagation

    NASA Astrophysics Data System (ADS)

    El Hady, Ahmed; Machta, Benjamin B.

    2015-03-01

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

  4. Ca channel gating during cardiac action potentials.

    PubMed

    Mazzanti, M; DeFelice, L J

    1990-10-01

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

  5. Ca channel gating during cardiac action potentials.

    PubMed

    Mazzanti, M; DeFelice, L J

    1990-10-01

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

  6. Ionic requirements for arterial action potential

    PubMed Central

    Keatinge, W. R.

    1968-01-01

    1. Strips of smooth muscle from common carotid arteries of sheep were electrically quiescent in solution containing Na 148 mM and Ca 2·5 mM. 2. When Ca was removed they became electrically active. Addition of low concentrations of Ca (0·025-0·075 mM) or Mg (0·025-0·750 mM) stopped their activity while ethylenediamine tetra-acetate (EDTA) (1·25 mM) accelerated it. 3. Replacement of Na by Tris or choline stopped the activity in Ca-free solution. After partial replacement of Na electrical activity could be restored by lowering the resting potential but after complete replacement of Na it could not. 4. In the presence of Ca (2·5 mM) small spikes could sometimes be induced after 20 min in Na-free Tris solution by lowering the resting potential by an increase in the external K concentration. 5. The results indicate that the depolarizing current of action potentials in this smooth muscle was largely carried by Na, although a little may have been carried by Ca in Ca-containing solutions. 6. The arteries in general resembled striated muscle rather than intestinal smooth muscle in these respects, but unlike striated muscle their action potentials were not stopped by tetrodotoxin. ImagesFig. 2 PMID:5639765

  7. Processes of carbon disulfide degradation under the action of a pulsed corona discharge

    NASA Astrophysics Data System (ADS)

    Kuznetsov, D. L.; Filatov, I. E.; Uvarin, V. V.

    2016-08-01

    Experiments on decomposition of carbon disulfide CS2 in air under the action of a pulsed nanosecond corona discharge have been carried out. The energetic efficiency of the degradation amounted to 290-340 g (kW h)-1, which is significantly higher than with the use of a corona discharge at a constant voltage. The main degradation products are sulfur dioxide SO2, carbonyl sulfide COS, sulfuric acid, and carbon dioxide. Processes occurring in pulsed corona discharge plasma and leading to carbon disulfide degradation are considered. Different methods of air purification from carbon disulfide are compared.

  8. Corrective Action Decision Document for Corrective Action Unit 423: Building 03-60 Underground Discharge Point, Tonopah Test Range, Nevada

    SciTech Connect

    DOE /NV

    1999-06-19

    This Corrective Action Decision Document (CADD) has been prepared for Corrective Action Unit (CAU) 423, Building 03-60 Underground Discharge Point (UDP) in accordance with the Federal Facility Agreement and Consent Order (FFACO) of 1996 that was agreed to by the US Department of Energy, Nevada Operations Office (DOE/NV); the Nevada Division of Environmental Protection (NDEP); and the U.S Department of Defense (FFACO, 1996). The CADD provides or references the specific information necessary to recommend a preferred corrective action for the single Corrective Action Site (CAS), 03-02-002-0308, within CAU 423. Corrective Action Unit 423 is located at the Tonopah Test Range (TTR), Nevada. The TTR is approximately 255 kilometers (km) (140 miles[mi]) northwest of Las Vegas, Nevada. The UDP is approximately 73 meters (m) (240 feet [ft]) northwest of the northwest corner of Building 03-60, the Auto Maintenance Shop. Corrective Action Unit 423 is comprised of the UDP and an associated discharge line extending from Building 03-60. The UDP received waste oil products from the Auto Maintenance Shop, a light-duty fleet maintenance shop in the Area 3 compound, from 1965 to 1989 or 1990 (DOE/NV, 1997).

  9. Corrective Action Investigation Plan for Corrective Action Unit 516: Septic Systems and Discharge Points, Nevada Test Site, Nevada, Rev. 0, Including Record of Technical Change No. 1

    SciTech Connect

    2003-04-28

    This Corrective Action Investigation Plan (CAIP) contains the U.S. Department of Energy (DOE), National Nuclear Security Administration Nevada Sites Office's (NNSA/NSO's) approach to collect the data necessary to evaluate corrective action alternatives appropriate for the closure of Corrective Action Unit (CAU) 516, Septic Systems and Discharge Points, Nevada Test Site (NTS), Nevada, under the Federal Facility Agreement and Consent Order. CAU 516 consists of six Corrective Action Sites: 03-59-01, Building 3C-36 Septic System; 03-59-02, Building 3C-45 Septic System; 06-51-01, Sump Piping, 06-51-02, Clay Pipe and Debris; 06-51-03, Clean Out Box and Piping; and 22-19-04, Vehicle Decontamination Area. Located in Areas 3, 6, and 22 of the NTS, CAU 516 is being investigated because disposed waste may be present without appropriate controls, and hazardous and/or radioactive constituents may be present or migrating at concentrations and locations that could potentially pose a threat to human health and the environment. Existing information and process knowledge on the expected nature and extent of contamination of CAU 516 are insufficient to select preferred corrective action alternatives; therefore, additional information will be obtained by conducting a corrective action investigation. The results of this field investigation will support a defensible evaluation of corrective action alternatives in the corrective action decision document. Record of Technical Change No. 1 is dated 3/2004.

  10. Corrective Action Investigation Plan for Corrective Action Unit No. 423: Building 03-60 Underground Discharge Point, Tonopah Test Range, Nevada

    SciTech Connect

    DOE /NV

    1997-10-01

    This Corrective Action Investigation Plan (CAIP) has been developed in accordance with the Federal Facility Agreement and Consent Order (FFACO) that was agreed to by the US Department of Energy, Nevada Operations Office (DOE/NV), the State of Nevada Division of Environmental Protection (NDEP), and the US Department of Defense. The CAIP is a document that provides or references all of the specific information for investigation activities associated with Corrective Action Units (CAUS) or Corrective Action Sites (CASs) (FFACO, 1996). As per the FFACO (1996), CASs are sites potentially requiring corrective action(s) and may include solid waste management units or individual disposal or release sites. Corrective Action Units consist of one or more CASs grouped together based on geography, technical similarity, or agency responsibility for the purpose of determining corrective actions. This CAIP contains the environmental sample collection objectives and the criteria for conducting site investigation activities at CAU No. 423, the Building 03-60 Underground Discharge Point (UDP), which is located in Area 3 at the Tonopah Test Range (TTR). The TTR, part of the Nellis Air Force Range, is approximately 225 kilometers (km) (140 miles [mi]) northwest of Las Vegas, Nevada (Figures 1-1 and 1-2). Corrective Action Unit No. 423 is comprised of only one CAS (No. 03-02-002-0308), which includes the Building 03-60 UDP and an associated discharge line extending from Building 03-60 to a point approximately 73 meters (m) (240 feet [ft]) northwest as shown on Figure 1-3.

  11. 40 CFR 230.72 - Actions controlling the material after discharge.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... and disposal sites where the potential for erosion, slumping or leaching of materials into the... discharge to minimize impact, for instance during periods of unusual high water flows, wind, wave, and...

  12. Plasma potential mapping of high power impulse magnetron sputtering discharges

    SciTech Connect

    Rauch, Albert; Mendelsberg, Rueben J.; Sanders, Jason M.; Anders, Andre

    2011-12-20

    Pulsed emissive probe techniques have been used to determine the plasma potential distribution of high power impulse magnetron sputtering (HiPIMS) discharges. An unbalanced magnetron with a niobium target in argon was investigated for pulse length of 100 μs at a pulse repetition rate of 100 Hz, giving a peak current of 170 A. The probe data were taken with a time resolution of 20 ns and a spatial resolution of 1 mm. It is shown that the local plasma potential varies greatly in space and time. The lowest potential was found over the target’s racetrack, gradually reaching anode potential (ground) several centimeters away from the target. The magnetic pre-sheath exhibits a funnel-shaped plasma potential resulting in an electric field which accelerates ions toward the racetrack. In certain regions and times, the potential exhibits weak local maxima which allow for ion acceleration to the substrate. Knowledge of the local E and static B fields lets us derive the electrons’ E×B drift velocity, which is about 105 m/s and shows structures in space and time.

  13. 28 CFR 50.7 - Consent judgments in actions to enjoin discharges of pollutants.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... exception to this policy in a specific case where extraordinary circumstances require a period shorter than... discharges of pollutants. 50.7 Section 50.7 Judicial Administration DEPARTMENT OF JUSTICE (CONTINUED... established as the policy of the Department of Justice to consent to a proposed judgment in an action...

  14. Corrective Action Plan for Corrective Action Unit 262: Area 25 Septic Systems and Underground Discharge Point, Nevada Test Site, Nevada

    SciTech Connect

    K. B. Campbell

    2002-06-01

    This Corrective Action Plan (CAP) provides selected corrective action alternatives and proposes the closure methodology for Corrective Action Unit (CAU) 262, Area 25 Septic Systems and Underground Discharge Point. CAU 262 is identified in the Federal Facility Agreement and Consent Order (FFACO) of 1996. Remediation of CAU 262 is required under the FFACO. CAU 262 is located in Area 25 of the Nevada Test Site (NTS), approximately 100 kilometers (km) (62 miles [mi]) northwest of Las Vegas, Nevada. The nine Corrective Action Sites (CASs) within CAU 262 are located in the Nuclear Rocket Development Station complex. Individual CASs are located in the vicinity of the Reactor Maintenance, Assembly, and Disassembly (R-MAD); Engine Maintenance, Assembly, and Disassembly (E-MAD); and Test Cell C compounds. CAU 262 includes the following CASs as provided in the FFACO (1996); CAS 25-02-06, Underground Storage Tank; CAS 25-04-06, Septic Systems A and B; CAS 25-04-07, Septic System; CAS 25-05-03, Leachfield; CAS 25-05-05, Leachfield; CAS 25-05-06, Leachfield; CAS 25-05-08, Radioactive Leachfield; CAS 25-05-12, Leachfield; and CAS 25-51-01, Dry Well. Figures 2, 3, and 4 show the locations of the R-MAD, the E-MAD, and the Test Cell C CASs, respectively. The facilities within CAU 262 supported nuclear rocket reactor engine testing. Activities associated with the program were performed between 1958 and 1973. However, several other projects used the facilities after 1973. A significant quantity of radioactive and sanitary waste was produced during routine operations. Most of the radioactive waste was managed by disposal in the posted leachfields. Sanitary wastes were disposed in sanitary leachfields. Septic tanks, present at sanitary leachfields (i.e., CAS 25-02-06,2504-06 [Septic Systems A and B], 25-04-07, 25-05-05,25-05-12) allowed solids to settle out of suspension prior to entering the leachfield. Posted leachfields do not contain septic tanks. All CASs located in CAU 262 are

  15. 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.

  16. 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

  17. Action potential broadening in a presynaptic channelopathy.

    PubMed

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

    2016-01-01

    Brain development and interictal function are unaffected in many paroxysmal neurological channelopathies, possibly explained by homoeostatic plasticity of synaptic transmission. Episodic ataxia type 1 is caused by missense mutations of the potassium channel Kv1.1, which is abundantly expressed in the terminals of cerebellar basket cells. Presynaptic action potentials of small inhibitory terminals have not been characterized, and it is not known whether developmental plasticity compensates for the effects of Kv1.1 dysfunction. Here we use visually targeted patch-clamp recordings from basket cell terminals of mice harbouring an ataxia-associated mutation and their wild-type littermates. Presynaptic spikes are followed by a pronounced afterdepolarization, and are broadened by pharmacological blockade of Kv1.1 or by a dominant ataxia-associated mutation. Somatic recordings fail to detect such changes. Spike broadening leads to increased Ca(2+) influx and GABA release, and decreased spontaneous Purkinje cell firing. We find no evidence for developmental compensation for inherited Kv1.1 dysfunction. PMID:27381274

  18. Detection and classification of raw action potential patterns in human Muscle Sympathetic Nerve Activity.

    PubMed

    Salmanpour, Aryan; Brown, Lyndon J; Shoemaker, J K

    2008-01-01

    The Muscle Sympathetic Nerve Activity (MSNA) consists of synchronous neural discharges separated by periods of neural silence dominated by heavy background noise. During measurement with electrodes, the raw MSNA signal is amplified, band-pass filtered, rectified and integrated. This integration process removes much neurophysiological information. In this paper a method for detecting a raw action potential (before the pre-amplifier) and filtered action potential (after the band-pass filter) is presented. This method is based on stationary wavelet transform (SWT) and a peak detection algorithm. Also, the detected action potentials were clustered using the k-means method and the cluster averages were calculated. The action potential detector and classification algorithm are evaluated using real MSNA recorded from three healthy subjects.

  19. 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

  20. Conduction velocity of antigravity muscle action potentials.

    PubMed

    Christova, L; Kosarov, D; Christova, P

    1992-01-01

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

  1. Closure Report for Corrective Action Unit 516: Septic Systems and Discharge Points

    SciTech Connect

    NSTec Environmental Restoration

    2007-02-01

    Corrective Action Unit (CAU) 516 is located in Areas 3, 6, and 22 of the Nevada Test Site. CAU 516 is listed in the Federal Facility Agreement and Consent Order of 1996 as Septic Systems and Discharge Points, and is comprised of six Corrective Action Sites (CASs): {sm_bullet} CAS 03-59-01, Bldg 3C-36 Septic System {sm_bullet} CAS 03-59-02, Bldg 3C-45 Septic System {sm_bullet} CAS 06-51-01, Sump and Piping {sm_bullet} CAS 06-51-02, Clay Pipe and Debris {sm_bullet} CAS 06-51-03, Clean Out Box and Piping {sm_bullet} CAS 22-19-04, Vehicle Decontamination Area The Nevada Division of Environmental Protection (NDEP)-approved corrective action alternative for CASs 06-51-02 and 22-19-04 is no further action. The NDEP-approved corrective action alternative for CASs 03-59-01, 03-59-02, 06-51-01, and 06-51-03 is clean closure. Closure activities included removing and disposing of total petroleum hydrocarbon (TPH)-impacted septic tank contents, septic tanks, distribution/clean out boxes, and piping. CAU 516 was closed in accordance with the NDEP-approved CAU 516 Corrective Action Plan (CAP). The closure activities specified in the CAP were based on the recommendations presented in the CAU 516 Corrective Action Decision Document (U.S. Department of Energy, National Nuclear Security Administration Nevada Site Office, 2004). This Closure Report documents CAU 516 closure activities. During closure activities, approximately 186 tons of hydrocarbon waste in the form of TPH-impacted soil and debris, as well as 89 tons of construction debris, were generated and managed and disposed of appropriately. Waste minimization techniques, such as field screening of soil samples and the utilization of laboratory analysis to characterize and classify waste streams, were employed during the performance of closure work.

  2. Assessing the potential global extent of SWOT river discharge observations

    NASA Astrophysics Data System (ADS)

    Pavelsky, Tamlin M.; Durand, Michael T.; Andreadis, Konstantinos M.; Beighley, R. Edward; Paiva, Rodrigo C. D.; Allen, George H.; Miller, Zachary F.

    2014-11-01

    Despite its importance as a major element of the global hydrologic cycle, runoff remains poorly constrained except at the largest spatial scales due to limitations of the global stream gauge network and inadequate data sharing. Efforts using remote sensing to infer runoff from discharge estimates are limited by characteristics of present-day sensors. The proposed Surface Water and Ocean Topography (SWOT) mission, a joint project between the United States and France, aims to substantially improve space-based estimates of river discharge. However, the extent of rivers observable by SWOT, likely limited to those wider than 50-100 m, remains unknown. Here, we estimate the extent of SWOT river observability globally using a downstream hydraulic geometry (DHG) approach combining basin areas from the Hydro1k and Hydrosheds elevation products, discharge from the Global Runoff Data Centre (GRDC), and width estimates from a global width-discharge relationship. We do not explicitly consider SWOT-specific errors associated with layover and other phenomena in this analysis, although they have been considered in formulation of the 50-100 m width thresholds. We compare the extent of SWOT-observable rivers with GRDC and USGS gauge datasets, the most complete datasets freely available to the global scientific community. In the continental US, SWOT would match USGS river basin coverage only at large scales (>25,000 km2). Globally, SWOT would substantially improve on GRDC observation extent: SWOT observation of 100 m (50 m) rivers will allow discharge estimation in >60% of 50,000 km2 (10,000 km2) river basins. In contrast, the GRDC observes fewer than 30% (15%) of these basins. SWOT could improve characterization of global runoff processes, especially with a 50 m observability threshold, but in situ gauge data remains essential and must be shared more freely with the international scientific community.

  3. Spatial distribution and accumulation of radicals arising in organic solids under the action of glow discharge

    NASA Astrophysics Data System (ADS)

    Raitsimring, A. M.; Kurshev, V. V.

    1994-12-01

    The method, based on analyzing the dipolar broadening of EPR spectra was applied for investigation of the spatial distribution of radicals generated by high-frequency glow discharge in organic molecular crystals (powders of malonic and dimethylmalonic acids) and glassy isopropanol contained electron scavenger. It was shown that in the first case the radical distribution does not depend on time of discharge. The radicals are generated in layer of size ˜.05-0.1 μm at a concentration of ˜2 10 20 cm -3. For the second case the distribution function was changed in the course of plasma treatment and the depth of radical generation was varied from 0.25 to 1.5 μm during the discharge action. Contribution of the various mechanisms of radical formation were evaluated and it was shown that ionic mechanism predominated. A kinetic model is proposed to describe both the radical accumulation and evolution of spatial distribution function in plasmolysis. The use of the model, method and obtained data for general and practical applications is discussed.

  4. Cell discharge correlates of posterior hypothalamic theta rhythm. Recipe for success in recording stable field potential.

    PubMed

    Bocian, Renata; Kłos-Wojtczak, Paulina; Konopacki, Jan

    2016-09-01

    The theta rhythm discovered in the posterior hypothalamus area (PHa) differs from theta observed in the hippocampal formation. In comparison to hippocampal spontaneous theta, the theta recorded in the PHa is rarely registered, has lower amplitude, often disappears, and sometimes returns after a few minutes. These features indicate that spontaneous theta recorded in the PHa is not an appropriate experimental model to search for the correlation between PHa cell discharges and local field potential. In this paper we present standard experimental conditions necessary to record theta-related cells in the PHa in anesthetized rats. Three pharmacological agents were used in the experiments to induce PHa theta rhythm in urethanized rats: carbachol (CCH), carbenoxolone and kainic acid, which are potent enough to induce well-synchronized PHa theta. However, CCH was found to be the best pharmacological tool to induce PHa theta oscillations, due to its longest duration of action and lack of preliminary epileptogenic effects. It seems that CCH-induced theta can be the most suitable pharmacological model for experiments with the use of protocol of long-lasting recordings of PHa theta-related cell discharges. PMID:27353451

  5. Selective effects of an octopus toxin on action potentials

    PubMed Central

    Dulhunty, Angela; Gage, Peter W.

    1971-01-01

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

  6. Closure Report for Corrective Action Unit 151: Septic Systems and Discharge Area, Nevada Test Site, Nevada

    SciTech Connect

    NSTec Environmental Restoration

    2008-04-01

    Corrective Action Unit (CAU) 151 is identified in the Federal Facility Agreement and Consent Order (FFACO) as Septic Systems and Discharge Area. CAU 151 consists of the following eight Corrective Action Sites (CASs), located in Areas 2, 12, and 18 of the Nevada Test Site, approximately 65 miles northwest of Las Vegas, Nevada: (1) CAS 02-05-01, UE-2ce Pond; (2) CAS 12-03-01, Sewage Lagoons (6); (3) CAS 12-04-01, Septic Tanks; (4) CAS 12-04-02, Septic Tanks; (5) CAS 12-04-03, Septic Tank; (6) CAS 12-47-01, Wastewater Pond; (7) CAS 18-03-01, Sewage Lagoon; and (8) CAS 18-99-09, Sewer Line (Exposed). CAU 151 closure activities were conducted according to the FFACO (FFACO, 1996; as amended February 2008) and the Corrective Action Plan for CAU 151 (U.S. Department of Energy, National Nuclear Security Administration Nevada Site Office, 2007) from October 2007 to January 2008. The corrective action alternatives included no further action, clean closure, and closure in place with administrative controls. CAU 151 closure activities are summarized in Table 1. Closure activities generated liquid remediation waste, sanitary waste, hydrocarbon waste, and mixed waste. Waste generated was appropriately managed and disposed. Waste that is currently staged onsite is being appropriately managed and will be disposed under approved waste profiles in permitted landfills. Waste minimization activities included waste characterization sampling and segregation of waste streams. Some waste exceeded land disposal restriction limits and required offsite treatment prior to disposal. Other waste meeting land disposal restrictions was disposed of in appropriate onsite or offsite landfills. Waste disposition documentation is included as Appendix C.

  7. Phosphorus in groundwater discharge - A potential source for lake eutrophication

    NASA Astrophysics Data System (ADS)

    Meinikmann, Karin; Hupfer, Michael; Lewandowski, Jörg

    2015-05-01

    Lake eutrophication has long been mainly associated with phosphorus (P) inputs from overland flow. The present study gives evidence that also groundwater can carry significant loads of dissolved P. We quantified P loads from groundwater to Lake Arendsee using near-shore measurements of P concentrations at a high spatial resolution and volume fluxes of lacustrine groundwater discharge (LGD) derived from a previous study. Results show that LGD accounts for more than 50% of the overall external P load, thus fuelling the eutrophication of the lake. Several different approaches of groundwater sampling (groundwater observation wells, temporary piezometers, and domestic wells) reveal a broad spatial heterogeneity of P concentrations in the subsurface catchment of the lake. The highest P concentrations (above 4 mg l-1) were found below a settled area along the southern lake shore. Contrary to expectations, other parameters (dissolved iron, ammonium, etc.) were not correlated with P, indicating that natural processes are superimposed by heavy contaminations. Both the intensity of the contamination and its proximity to the lake inhibit nutrient retention within vadose zone and aquifer and allow significant P loads to be discharged into the lake. Although the groundwater quality was investigated intensely, the results eventually give no clear evidence of the location and sources of the pollution. As a consequence, measures to decrease LGD-derived P loads cannot target the contamination at its source in the catchment. They need to be implemented in the riparian area to eliminate groundwater P directly before it enters the lake.

  8. Potential effects of low-volume effluent discharges on past-practice vadose zone contamination

    SciTech Connect

    Barnett, D.B., Westinghouse Hanford

    1996-07-30

    Collard, L. B., J. D. Davis, D. B. Barnett, 1996, Potential Effects of Low-Volume Effluent Discharges on Past Practice Vadose Zone Contamination: WHC-SD-LEF-ER-001, Westinghouse Hanford Company, Richland Washington. This document estimates the behavior of extremely low-discharges of water in the unsaturated zone in the vicinity of past-practice facilities.

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

    PubMed

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

    2016-10-01

    An adaptive integration method is proposed for computing cardiac action potential models accurately and efficiently. Time steps are adaptively chosen by solving a quadratic formula involving the first and second derivatives of the membrane action potential. To improve the numerical accuracy, we devise an extremum-locator (el) function to predict the local extremum when approaching the peak amplitude of the action potential. In addition, the time step restriction (tsr) technique is designed to limit the increase in time steps, and thus prevent the membrane potential from changing abruptly. The performance of the proposed method is tested using the Luo-Rudy phase 1 (LR1), dynamic (LR2), and human O'Hara-Rudy dynamic (ORd) ventricular action potential models, and the Courtemanche atrial model incorporating a Markov sodium channel model. Numerical experiments demonstrate that the action potential generated using the proposed method is more accurate than that using the traditional Hybrid method, especially near the peak region. The traditional Hybrid method may choose large time steps near to the peak region, and sometimes causes the action potential to become distorted. In contrast, the proposed new method chooses very fine time steps in the peak region, but large time steps in the smooth region, and the profiles are smoother and closer to the reference solution. In the test on the stiff Markov ionic channel model, the Hybrid blows up if the allowable time step is set to be greater than 0.1ms. In contrast, our method can adjust the time step size automatically, and is stable. Overall, the proposed method is more accurate than and as efficient as the traditional Hybrid method, especially for the human ORd model. The proposed method shows improvement for action potentials with a non-smooth morphology, and it needs further investigation to determine whether the method is helpful during propagation of the action potential. PMID:27639239

  10. Corrective Action Decision Document for Corrective Action Unit 151: Septic Systems and Discharge Area, Nevada Test Site, Nevada, Rev. No.: 0

    SciTech Connect

    Grant Evenson

    2006-05-01

    This Corrective Action Decision Document has been prepared for Corrective Action Unit (CAU) 151, Septic Systems and Discharge Area, at the Nevada Test Site, Nevada, according to the ''Federal Facility Agreement and Consent Order'' (FFACO) (1996). Corrective Action Unit 151 is comprised of eight corrective action sites (CASs): (1) CAS 02-05-01, UE-2ce Pond; (2) CAS 12-03-01, Sewage Lagoons (6); (3) CAS 12-04-01, Septic Tanks; (4) CAS 12-04-02, Septic Tanks; (5) CAS 12-04-03, Septic Tank; (6) CAS 12-47-01, Wastewater Pond; (7) CAS 18-03-01, Sewage Lagoon; and (8) CAS 18-99-09, Sewer Line (Exposed). The purpose of this Corrective Action Decision Document is to identify and provide the rationale for the recommendation of corrective action alternatives (CAAs) for each of the eight CASs within CAU 151. Corrective action investigation (CAI) activities were performed from September 12 through November 18, 2005, as set forth in the CAU 151 Corrective Action Investigation Plan and Record of Technical Change No. 1. Additional confirmation sampling was performed on December 9, 2005; January 10, 2006; and February 13, 2006. Analytes detected during the CAI were evaluated against appropriate final action levels (FALs) to identify the contaminants of concern for each CAS. The results of the CAI identified contaminants of concern at two of the eight CASs in CAU 151 and required the evaluation of CAAs. Assessment of the data generated from investigation activities conducted at CAU 151 revealed the following: (1) Soils at CASs 02-05-01, 12-04-01, 12-04-02, 12-04-03, 12-47-01, 18-03-01, 18-99-09, and Lagoons B through G of CAS 12-03-01 do not contain contamination at concentrations exceeding the FALs. (2) Lagoon A of CAS 12-03-01 has arsenic above FALs in shallow subsurface soils. (3) One of the two tanks of CAS 12-04-01, System No.1, has polychlorinated biphenyls (aroclor-1254), trichloroethane, and cesium-137 above FALs in the sludge. Both CAS 12-04-01, System No.1 tanks contain

  11. Flood Frequency Estimates and Documented and Potential Extreme Peak Discharges in Oklahoma

    USGS Publications Warehouse

    Tortorelli, Robert L.; McCabe, Lan P.

    2001-01-01

    Knowledge of the magnitude and frequency of floods is required for the safe and economical design of highway bridges, culverts, dams, levees, and other structures on or near streams; and for flood plain management programs. Flood frequency estimates for gaged streamflow sites were updated, documented extreme peak discharges for gaged and miscellaneous measurement sites were tabulated, and potential extreme peak discharges for Oklahoma streamflow sites were estimated. Potential extreme peak discharges, derived from the relation between documented extreme peak discharges and contributing drainage areas, can provide valuable information concerning the maximum peak discharge that could be expected at a stream site. Potential extreme peak discharge is useful in conjunction with flood frequency analysis to give the best evaluation of flood risk at a site. Peak discharge and flood frequency for selected recurrence intervals from 2 to 500 years were estimated for 352 gaged streamflow sites. Data through 1999 water year were used from streamflow-gaging stations with at least 8 years of record within Oklahoma or about 25 kilometers into the bordering states of Arkansas, Kansas, Missouri, New Mexico, and Texas. These sites were in unregulated basins, and basins affected by regulation, urbanization, and irrigation. Documented extreme peak discharges and associated data were compiled for 514 sites in and near Oklahoma, 352 with streamflow-gaging stations and 162 at miscellaneous measurements sites or streamflow-gaging stations with short record, with a total of 671 measurements.The sites are fairly well distributed statewide, however many streams, large and small, have never been monitored. Potential extreme peak-discharge curves were developed for streamflow sites in hydrologic regions of the state based on documented extreme peak discharges and the contributing drainage areas. Two hydrologic regions, east and west, were defined using 98 degrees 15 minutes longitude as the

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

    PubMed Central

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

    2015-01-01

    The objective was to develop a physical action potential generator (Paxon) with the ability to generate a stable, repeatable, programmable, and physiological-like action potential. The Paxon has an equivalent of 40 nodes of Ranvier that were mimicked using resin embedded gold wires (Ø = 20 μm). These nodes were software controlled and the action potentials were initiated by a start trigger. Clinically used Ag-AgCl electrodes were coupled to the Paxon for functional testing. The Paxon's action potential parameters were tunable using a second order mathematical equation to generate physiologically relevant output, which was accomplished by varying the number of nodes involved (1–40 in incremental steps of 1) and the node drive potential (0–2.8 V in 0.7 mV steps), while keeping a fixed inter-nodal timing and test electrode configuration. A system noise floor of 0.07 ± 0.01 μV was calculated over 50 runs. A differential test electrode recorded a peak positive amplitude of 1.5 ± 0.05 mV (gain of 40x) at time 196.4 ± 0.06 ms, including a post trigger delay. The Paxon's programmable action potential like signal has the possibility to be used as a validation test platform for medical surface electrodes and their attached systems. PMID:26539072

  13. Corrective Action Investigation Plan for Corrective Action Unit 406: Area 3 Building 03-74 and Building 03-58 Under ground Discharge Points and Corrective Action Unit 429: Area 3 Building 03-55 and Area 9 Building 09-52 Underground Discharge Points, Tonopah Test Range, Nevada

    SciTech Connect

    DOE /NV

    1999-05-20

    This Corrective Action Investigation Plan (CAIP) has been developed in accordance with the Federal Facility Agreement and Consent Order (FFACO) that was agreed to by the US Department of Energy, Nevada Operations Office (DOE/NV); the State of Nevada Division of Environmental Protection (NDEP); and the US Department of Defense (FFACO, 1996). The CAIP is a document that provides or references all of the specific information for investigation activities associated with Corrective Action Units (CAUs) or Corrective Action Sites (CASs). According to the FFACO (1996), CASs are sites potentially requiring corrective action(s) and may include solid waste management units or individual disposal or release sites. Corrective Action Units consist of one or more CASs grouped together based on geography, technical similarity, or agency responsibility for the purpose of determining corrective actions. This CAIP contains the environmental sample collection objectives and the criteria for conducting site investigation activities at the Underground Discharge Points (UDPs) included in both CAU 406 and CAU 429. The CAUs are located in Area 3 and Area 9 of the Tonopah Test Range (TTR). The TTR, included in the Nellis Air Force Range, is approximately 255 kilometers (km) (140 miles [mi]) northwest of Las Vegas, Nevada.

  14. [On the theory of action potential propagation in plant cells].

    PubMed

    Sizonenko, V L; Kovalenko, N I

    2012-01-01

    The distribution of an electric field in plant cells and zooblasts has been investigated at propagation of the action potential. The behavior of ions in the cytoplasm and in the extracellular fluid has been described with the equations of electric charge motion in the electrolytes. It has been shown that the action potential causes an electric potential change not only in the depth of the cytoplasm but also in the extracellular area far from the lipidic bilayer. The biomembrane resistance has been expressed by physical parameters of a cell, such as ionic diffusion coefficient in fluid, Debye-Huckel radius, dielectric conductivity etc. The presence of breakings in the action potential diagrams has been explained as a result of insufficient resolving power of the measuring devices at the instant the sodium ionic canals of the bilayer opens. PMID:23035528

  15. The metabolic energy cost of action potential velocity

    NASA Astrophysics Data System (ADS)

    Crotty, Patrick; Sangrey, Thomas; Levy, William

    2006-03-01

    Voltage changes in neurons and other active cells are caused by the passage of ions across the cell membrane. These ionic currents depend on the transmembrane ion concentration gradients, which in unmyelinated axons are maintained during rest and restored after electrical activity by an ATPase sodium-potassium exchanger in the membrane. The amount of ATP consumed by this exchanger can be taken as the metabolic energy cost of any electrical activity in the axon. We use this measure, along with biophysical models of voltage-gated sodium and potassium ion channels, to quantify the energy cost of action potentials propagating in squid giant axons. We find that the energy of an action potential can be naturally divided into three separate components associated with different aspects of the action potential. We calculate these energy components as functions of the ion channel densities and axon diameters and find that the component associated with the rising phase and velocity of the action potential achieves a minimum near the biological values of these parameters. This result, which is robust with respect to other parameters such as temperature, suggests that evolution has optimized the axon for the energy of the action potential wavefront.

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

    PubMed

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

    2014-02-01

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

  17. Probe measurements of the space potential in a radio frequency discharge

    NASA Astrophysics Data System (ADS)

    Godyak, V. A.; Piejak, R. B.

    1990-10-01

    The dc and radio frequency (rf) components (and harmonics) of the probe potential have been measured in the midplane of a 13.56-MHz parallel-plane rf discharge in argon over a wide range of discharge voltages and at gas pressures between 10 mTorr and 1.0 Torr. rf potential measurements were made with different input capacitances to determine the true magnitude of the rf plasma potential and the probe capacitance. For a symmetrically driven rf discharge, the rf plasma potential Vrf is mainly composed of the second harmonic of the driving voltage Vdr over a wide range of gas pressures. For high values of Vdr, Vrf ≊0.1 Vdr while the dc probe potential Vdc is about 0.4 Vdr. These results are in good agreement with corresponding theoretical predictions found in the literature. For an asymmetrically driven rf discharge with equal electrode area, the rf plasma potential has an additional fundamental harmonic component equal to half the rf driving voltage. Values of rf plasma potential and probe capacitance given here allow us to specify the requirements on probe circuitry for different kinds of probe measurements in rf discharges.

  18. Corrective action investigation plan for Corrective Action Unit Number 423: Building 03-60 Underground Discharge Point, Tonopah Test Range, Nevada

    SciTech Connect

    1997-10-27

    This Corrective Action Investigation Plan (CAIP) contains the environmental sample collection objectives and the criteria for conducting site investigation activities at Corrective Action Unit (CAU) Number 423, the Building 03-60 Underground Discharge Point (UDP), which is located in Area 3 at the Tonopah Test Range (TTR). The TTR, part of the Nellis Air Force Range, is approximately 225 kilometers (140 miles) northwest of Las Vegas, Nevada. CAU Number 423 is comprised of only one Corrective Action Site (CAS) which includes the Building 03-60 UDP and an associated discharge line extending from Building 03-60 to a point approximately 73 meters (240 feet) northwest. The UDP was used between approximately 1965 and 1990 to dispose of waste fluids from the Building 03-60 automotive maintenance shop. It is likely that soils surrounding the UDP have been impacted by oil, grease, cleaning supplies and solvents as well as waste motor oil and other automotive fluids released from the UDP.

  19. Pre & Postsynaptic Tuning of Action Potential Timing by Spontaneous GABAergic Activity

    PubMed Central

    Caillard, Olivier

    2011-01-01

    Frequency and timing of action potential discharge are key elements for coding and transfer of information between neurons. The nature and location of the synaptic contacts, the biophysical parameters of the receptor-operated channels and their kinetics of activation are major determinants of the firing behaviour of each individual neuron. Ultimately the intrinsic excitability of each neuron determines the input-output function. Here we evaluate the influence of spontaneous GABAergic synaptic activity on the timing of action potentials in Layer 2/3 pyramidal neurones in acute brain slices from the somatosensory cortex of young rats. Somatic dynamic current injection to mimic synaptic input events was employed, together with a simple computational model that reproduce subthreshold membrane properties. Besides the well-documented control of neuronal excitability, spontaneous background GABAergic activity has a major detrimental effect on spike timing. In fact, GABAA receptors tune the relationship between the excitability and fidelity of pyramidal neurons via a postsynaptic (the reversal potential for GABAA activity) and a presynaptic (the frequency of spontaneous activity) mechanism. GABAergic activity can decrease or increase the excitability of pyramidal neurones, depending on the difference between the reversal potential for GABAA receptors and the threshold for action potential. In contrast, spike time jitter can only be increased proportionally to the difference between these two membrane potentials. Changes in excitability by background GABAergic activity can therefore only be associated with deterioration of the reliability of spike timing. PMID:21789249

  20. Corrective action plan for CAU Number 339: Area 12 Fleet Operations, Steam Cleaning Discharge Area, Nevada Test Site

    SciTech Connect

    1997-05-01

    The purpose of this Corrective Action Plan (CAP) is to provide the method for implementing the corrective action alternative as provided in the Corrective Action Decision Document (CADD). Detailed information of the site history and results of previous characterizations can be found in the Work Plan, the Preliminary Investigation Report, and the Phase 2 Characterization Report. Previous characterization investigations were completed as a condition of the Temporary Water Pollution Control Permit issued by the Nevada Division of Environmental Protection (NDEP) on July 14, 1992. The scope of this report is to prepare a CAP based upon the selected remedial alternative for closure of the Area 12, Building 12-16 Fleet Operations steam cleaning discharge area. The effluent discharge area has been impacted by volatile organic compounds (VOCs) and total petroleum hydrocarbons (TPH) as oil. The maximum hydrocarbon and VOC concentrations detected in the Preliminary and Phase 2 Site Characterization Investigations are summarized.

  1. 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.

  2. 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.

  3. 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…

  4. 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…

  5. 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

  6. Corrective Action Investigation Plan for Corrective Action Unit 151: Septic Systems and Discharge Area, Nevada Test Site, Nevada, Rev. No.: 0

    SciTech Connect

    David A. Strand

    2004-06-01

    This Corrective Action Investigation Plan (CAIP) contains project-specific information for conducting site investigation activities at Corrective Action Unit (CAU) 151: Septic Systems and Discharge Area, Nevada Test Site, Nevada. Information presented in this CAIP includes facility descriptions, environmental sample collection objectives, and criteria for the selection and evaluation of environmental corrective action alternatives. Corrective Action Unit 151 is located in Areas 2, 12, 18, and 20 of the Nevada Test Site, which is 65 miles northwest of Las Vegas, Nevada. Corrective Action Unit 151 is comprised of the nine Corrective Action Sites (CAS) listed below: (1) 02-05-01, UE-2ce Pond; (2) 12-03-01, Sewage Lagoons (6); (3) 12-04-01, Septic Tanks; (4) 12-04-02, Septic Tanks; (5) 12-04-03, Septic Tank; (6) 12-47-01, Wastewater Pond; (7) 18-03-01, Sewage Lagoon; (8) 18-99-09, Sewer Line (Exposed); and (9) 20-19-02, Photochemical Drain. The CASs within CAU 151 are discharge and collection systems. Corrective Action Site 02-05-01 is located in Area 2 and is a well-water collection pond used as a part of the Nash test. Corrective Action Sites 12-03-01, 12-04-01, 12-04-02, 12-04-03, and 12-47-01 are located in Area 12 and are comprised of sewage lagoons, septic tanks, associated piping, and two sumps. The features are a part of the Area 12 Camp housing and administrative septic systems. Corrective Action Sites 18-03-01 and 18-99-09 are located in the Area 17 Camp in Area 18. These sites are sewage lagoons and associated piping. The origin and terminus of CAS 18-99-09 are unknown; however, the type and configuration of the pipe indicates that it may be a part of the septic systems in Area 18. Corrective Action Site 20-19-02 is located in the Area 20 Camp. This site is comprised of a surface discharge of photoprocessing chemicals.

  7. 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

  8. Potential effects of runoff, fluvial sediment, and nutrient discharges on the coral reefs of Puerto Rico

    USGS Publications Warehouse

    Larsen, M.C.; Webb, R.M.T.

    2009-01-01

    Coral reefs, the foundation and primary structure of many highly productive and diverse tropical marine ecosystems, have been degraded by human activity in much of the earth's tropical oceans. To contribute to improved understanding of this problem, the potential relation between river sediment and nutrient discharges and degradation of coral reefs surrounding Puerto Rico was studied using streamflow, suspended-sediment, and water-quality data. Mean annual runoff for the 8711 km2 island is 911 mm, about 57% of mean annual precipitation (1600 mm). Mean annual suspended-sediment discharge from Puerto Rico to coastal waters is estimated at 2.7-9.0 million metric tonnes. Storm runoff transports a substantial part of sediment: the highest recorded daily sediment discharge is 1-3.6 times the mean annual sediment discharge. Hurricane Georges (1998) distributed an average of 300 mm of rain across the island, equivalent to a volume of about 2.6 billion m3. Runoff of more than 1.0 billion m3 of water and as much as 5 to 10 million metric tonnes of sediment were discharged to the coast and shelf. Nitrogen and phosphorous concentrations in river waters are as much as 10 times the estimated presettlement levels. Fecal coliform and fecal streptococcus concentrations in many Puerto Rico rivers are near or above regulatory limits. Unlike sediment discharges, which are predominantly episodic and intense, river-borne nutrient and fecal discharge is a less-intense but chronic stressor to coral reefs found near the mouths of rivers. Negative effects of riverderived sediment and nutrient discharge on coral reefs are especially pronounced on the north, southwest, and west coasts.

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

    PubMed

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

    2015-01-01

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

  10. Corrective Action Decision Document for Corrective Action Unit 516: Septic Systems and Discharge Points, Nevada Test Site, Nevada, Rev. No.: 1 with ROTC 1

    SciTech Connect

    Alfred N. Wickline

    2004-04-01

    This Corrective Action Decision Document (CADD) has been prepared for Corrective Action Unit (CAU) 516, Septic Systems and Discharge Points, Nevada Test Site, Nevada, in accordance with the ''Federal Facility Agreement and Consent Order'' (1996). Corrective Action Unit 516 is comprised of the following Corrective Action Sites (CASs): (1) 03-59-01 - Bldg 3C-36 Septic System; (2) 03-59-02 - Bldg 3C-45 Septic System; (3) 06-51-01 - Sump and Piping; (4) 06-51-02 - Clay Pipe and Debris; (5) 06-51-03 - Clean Out Box and Piping; and (7) 22-19-04 - Vehicle Decontamination Area. The purpose of this CADD is to identify and provide the rationale for the recommendation of an acceptable corrective action alternative for each CAS within CAU 516. Corrective action investigation activities were performed between July 22 and August 14, 2003, as set forth in the Corrective Action Investigation Plan. Supplemental sampling was conducted in late 2003 and early 2004.

  11. Shockwave-induced compound action potentials in the peripheral nerve.

    PubMed

    Wehner, H D; Sellier, K

    1981-01-01

    To verify a presumed interaction between shockwaves arisen by impacts of high velocity projectiles and nervous tissue an electrophysiological experiment is performed with the following results: In peripheral nerves regular compound action potentials (CAPs) are provoked by shockwaves the amplitudes of which are increased corresponding to the pressure intensity of the shockwaves. The nerve shows no electrical activity below a certain pressure threshold (0.75 bar). Saturation of the CAP amplitude occurs beyond a pressure limit of 8 bar.

  12. Compound muscle action potential cartography of an accessory peroneal nerve.

    PubMed

    Van Dijk, J G; Van der Hoeven, B J

    1998-10-01

    In daily practice, accessory peroneal nerves (APNs) are detected in less than the 18-25% of legs, as revealed by systematic searches. In one APN case, compound muscle action potential cartography showed that the APN was only apparent when the recording electrode was placed over a small lateral region of the extensor digitorum brevis muscle. Effects of recording site can explain why many APNs go unrecognized.

  13. Warm Body Temperature Facilitates Energy Efficient Cortical Action Potentials

    PubMed Central

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

    2012-01-01

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

  14. Potentiation of antitumor drug action by centrophenoxine: specificity.

    PubMed

    Sladek, N E

    1977-05-01

    The cytotoxic action of certain antitumor agents is potentiated by centrophenoxine although centrophenoxine itself is not an antitumor agent. Previous investigations have suggested that centrophenoxine might potentiate the cytotoxicity produced by antitumor drugs that alkylate, and other modalities that damage, DNA, but that it would not potentiate the cytotoxicity produced by antitumor drugs that inflict cellular damage in other ways. To test this hypothesis, the antitumor effects of X-irradiation UV-irradiation, alkylating agents and antitumor drugs that are not ordinarily considered to be alkylating agents were determined in the presence and absence of centrophenoxine. Mouse P388 lymphoma cells growing in static suspension culture were used as the experimental tumor. The cytotoxic action of most alkylating agents was found to be potentiated by centrophenoxine; Included in this group were several difunctional nitrogen mustards, two ethylenimines, a nitrosourea and mitomycin C. Greatest enhancement, 7-fold, was of chlorambucil antitumor activity. Centrophenoxine did not potentiate the lethality of X- or UV-irradiation or the cytotoxicity of several antineoplastic drugs that are not alkylating agents.

  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. Emergency assessment of potential debris-flow peak discharges, Missionary Ridge fire, Colorado

    USGS Publications Warehouse

    Cannon, Susan H.; Rea, Alan H.; Gleason, J. Andrew; Garcia, Stephen P.

    2002-01-01

    These maps present the results of assessments of peak discharges that can potentially be generated by debris flows issuing from the basins burned by the Missionary Ridge fire of June 9 through July 14, 2002, near Durango, Colorado. The maps are based on a regression model for debris-flow peak discharge normalized by average storm intensity as a function of basin gradient and burned extent, and limited field checking. A range of potential peak discharges that could be produced from each of the burned basins between 1 ft3/s (0.03 m3/s) and 6,446 ft3/s (183 m3/s) is calculated for the 5-year, 1-hour storm of 0.80 inches (20 mm). Potential peak discharges between 1 ft3/s (0.03 m3/s) and >8,000 ft3/s (227 m3/s) are calculated for the 25-year, 1-hour storm of 1.3 inches (33 mm) and for the 100-year, 1-hour storm of 1.8 inches (46 mm). These maps are intended for use by emergency personnel to aid in the preliminary design of mitigation measures, and for the planning of evacuation timing and routes.

  17. The characteristics of action potentials in primo vessels and the effects of acetylcholine injection to the action potentials.

    PubMed

    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.

  18. Atrial action potential heterogeneity measured by unipolar electrograms.

    PubMed

    Vigmond, Edward J; Tsoi, Vincent; Pagé, Pierre

    2006-01-01

    Vagally-induced action potential duration (APD) heterogeneity can lead to the breakdown of atrial flutter into fibrillation. The exact distribution of vagal mediated effects in the atria is unknown, however. This study analyzed canine electrograms in order to determine changes in APD. Electrograms were recorded under control, and left and right vagal nerve stimulation. Simulations in a computer model were first performed in order to determine how local acetylcholine concentrations affect electrograms. Two measures were investigated to assess APD changes. Results indicate that APD is reduced nonuniformly, and contralateral effects were seen.

  19. 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.

  20. Modification of surface layers of copper under the action of the volumetric discharge initiated by an avalanche electron beam in nitrogen and CO2 at atmospheric pressure

    NASA Astrophysics Data System (ADS)

    Shulepov, M. A.; Akhmadeev, Yu. Kh.; Tarasenko, V. F.; Kolubaeva, Yu. A.; Krysina, O. V.; Kostyrya, I. D.

    2011-05-01

    The results of experimental investigations of the action of the volumetric discharge initiated by an avalanche electron beam on the surface of copper specimens are presented. The volumetric (diffuse) discharge in nitrogen and CO2 at atmospheric pressure was initiated by applying high voltage pulses of nanosecond duration to a tubular foil cathode. It has been found that the treatment of a copper surface by this type of discharge increases the hardness of the surface layer due to oxidation.

  1. Exploring the Potential of Table-Top X-Ray Lasers and Capillary Discharge for Applications

    SciTech Connect

    Shlyaptev, V N; Dunn, J; Smith, R F; Moon, S J; Fournier, K B; Nilsen, J; Osterheld, A L; Kuba, J; Wootton, A J; Lee, R W; Rocca, J J; Rahman, A; Hammarsten, E; Filevich, J; Jankovska, E; Marconi, M C; Fornaciari, N; Buchenauer, D; Hender, H A; Kari,M S; Kanouff, M; Dimkoff, J; Kubiak, G; Shimkaveg, G; Silfvast, W T

    2003-05-08

    The advantages of using of table top x-ray lasers (XRLs) for different applications have been described. Examples of the first successful use of XRLs, the current efforts in applying them and the potential applications where an XRL can be used in future have been discussed. Modeling results showing the possibility of 3-4 times shorter wavelength capillary discharge x-ray lasers and calculated spectrum of Xe capillary EUV source are presented.

  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. 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…

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

    PubMed Central

    2012-01-01

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

  6. Transforming echoes into pseudo-action potentials for classifying plants.

    PubMed

    Kuc, R

    2001-10-01

    Animals perceive their environment by converting sensory stimuli into action potentials, or temporal point processes, that are interpreted by the brain. This paper investigates the information content of point processes extracted from echoes from in situ plants in an effort to understand how bats recognize landmarks in the field. A mobile sonar converts echoes into biologically similar temporal point processes. termed pseudo-action potentials (PAPs), whose inter-PAP interval relates to echo amplitude. The sonar forms a sector scan of an object to produce a spatial-temporal PAP field. Classifier neurons apply delays and coincidence detection to the PAP field to identify three distinct echo types, glints, blobs, and fuzz, which characterize plant features. Glints are large amplitude echoes exhibiting coherence over successive echoes in the sector scan, typically produced by favorably oriented isolated specular reflectors. Blobs are large echoes lacking coherence, typically bordering glints or formed by collections of interfering reflectors. Fuzz represents weak echoes, typically produced by collection of weak scatterers or by reflectors on the beam periphery. A small mirror reflector models a flat leaf surface and motivates the glint criteria. Classifiers are applied to experimental data from two types of tree trunks, a glint-producing sycamore (Platanus occidenatalis) and a glint-absent Norway maple (Acer platanoides) and two plants, a glint-producing rhododendron (Rhododendron maximus) and a glint-absent yew (Taxus media). We speculate that our narrow-band sonar models the activity of a single frequency bin in the frequency-modulated (FM) sweep emitted by bats, and that one function of the frequency bins in the FM sweep is to form a sector scan of the environment.

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

    PubMed Central

    Victor, Jonathan D.

    2011-01-01

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

  8. Tactile Stimulation Evokes Long-Lasting Potentiation of Purkinje Cell Discharge In Vivo

    PubMed Central

    Ramakrishnan, K. B.; Voges, Kai; De Propris, Licia; De Zeeuw, Chris I.; D’Angelo, Egidio

    2016-01-01

    In the cerebellar network, a precise relationship between plasticity and neuronal discharge has been predicted. However, the potential generation of persistent changes in Purkinje cell (PC) spike discharge as a consequence of plasticity following natural stimulation patterns has not been clearly determined. Here, we show that facial tactile stimuli organized in theta-patterns can induce stereotyped N-methyl-D-aspartate (NMDA) and gamma-aminobutyric acid (GABA-A) receptor-dependent changes in PCs and molecular layer interneurons (MLIs) firing: invariably, all PCs showed a long-lasting increase (Spike-Related Potentiation or SR-P) and MLIs a long-lasting decrease (Spike-Related Suppression or SR-S) in baseline activity and spike response probability. These observations suggests that tactile sensory stimulation engages multiple long-term plastic changes that are distributed along the mossy fiber-parallel fiber (MF-PF) pathway and operate synergistically to potentiate spike generation in PCs. In contrast, theta-pattern electrical stimulation (ES) of PFs indistinctly induced SR-P and SR-S both in PCs and MLIs, suggesting that tactile sensory stimulation preordinates plasticity upstream of the PF-PC synapse. All these effects occurred in the absence of complex spike changes, supporting the theoretical prediction that PC activity is potentiated when the MF-PF system is activated in the absence of conjunctive climbing fiber (CF) activity. PMID:26924961

  9. Physical and chemical properties of tungsten oxide nanoparticles obtained in plasma discharge under ultrasonic action

    NASA Astrophysics Data System (ADS)

    Bulychev, N. A.; Kazaryan, M. A.

    2015-12-01

    In this study, plasma discharge in a liquid at intensive ultrasonic field above the cavitation threshold has been proven to be of great interest for initiation of various physical and chemical processes. In such surcharge, nanoparticles of tungsten oxide with controlled size and shape and narrow particle size distribution have been synthesized. Further exploration of synthesized nanoparticles has demonstrated that the factor of ultrasonic cavitation during the synthesis substantially affects physical and chemical characteristics of nanoparticles. Similar procedure might be effective for compounds of tungsten and rare-earth elements.

  10. 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

  11. HF echoes from ionization potentially produced by high-altitude discharges

    SciTech Connect

    Roussel-Dupre, R.; Fitzgerald, T.J.; Symbalisty, E.

    1997-04-01

    In this paper the authors report on recent radar measurements taken during the month of October 1994 with the LDG HF radar in the Ivory Coast, Africa as part of the International Equatorial Electrojet Year. The purpose of this experimental effort in part was to study the effects of thunderstorms on the ionosphere. At the same time, the authors decided to carry out a set of experiments of an exploratory nature to look for echoes that could potentially arise from ionization produced in the mesosphere. The two leading candidates for producing transient ionization in the mesosphere are meteors and high-altitude discharges. Each is discussed in the context of these measurements.

  12. Potential health implications of water resources depletion and sewage discharges in the Republic of Macedonia.

    PubMed

    Hristovski, Kiril D; Pacemska-Atanasova, Tatjana; Olson, Larry W; Markovski, Jasmina; Mitev, Trajce

    2016-08-01

    Potential health implications of deficient sanitation infrastructure and reduced surface water flows due to climate change are examined in the case study of the Republic of Macedonia. Changes in surface water flows and wastewater discharges over the period 1955-2013 were analyzed to assess potential future surface water contamination trends. Simple model predictions indicated a decline in surface water hydrology over the last half century, which caused the surface waters in Macedonia to be frequently dominated by >50% of untreated sewage discharges. The surface water quality deterioration is further supported by an increasing trend in modeled biochemical oxygen demand trends, which correspond well with the scarce and intermittent water quality data that are available. Facilitated by the climate change trends, the increasing number of severe weather events is already triggering flooding of the sewage-dominated rivers into urban and non-urban areas. If efforts to develop a comprehensive sewage collection and treatment infrastructure are not implemented, such events have the potential to increase public health risks and cause epidemics, as in the 2015 case of a tularemia outbreak.

  13. Potential health implications of water resources depletion and sewage discharges in the Republic of Macedonia.

    PubMed

    Hristovski, Kiril D; Pacemska-Atanasova, Tatjana; Olson, Larry W; Markovski, Jasmina; Mitev, Trajce

    2016-08-01

    Potential health implications of deficient sanitation infrastructure and reduced surface water flows due to climate change are examined in the case study of the Republic of Macedonia. Changes in surface water flows and wastewater discharges over the period 1955-2013 were analyzed to assess potential future surface water contamination trends. Simple model predictions indicated a decline in surface water hydrology over the last half century, which caused the surface waters in Macedonia to be frequently dominated by >50% of untreated sewage discharges. The surface water quality deterioration is further supported by an increasing trend in modeled biochemical oxygen demand trends, which correspond well with the scarce and intermittent water quality data that are available. Facilitated by the climate change trends, the increasing number of severe weather events is already triggering flooding of the sewage-dominated rivers into urban and non-urban areas. If efforts to develop a comprehensive sewage collection and treatment infrastructure are not implemented, such events have the potential to increase public health risks and cause epidemics, as in the 2015 case of a tularemia outbreak. PMID:27441863

  14. Abiotic synthesis of purines and other heterocyclic compounds by the action of electrical discharges

    NASA Technical Reports Server (NTRS)

    Yuasa, S.; Flory, D.; Basile, B.; Oro, J.

    1984-01-01

    The synthesis of purines and pyrimidines using Oparin-Urey-type primitive earth atmospheres has been demonstrated by reacting methane, ethane, and ammonia in electrical discharges. Adenine, guaine, 4-aminoimidazole-5-carboxamide (AICA), and isocytosine have been identified by UV spectrometry and paper chromatography as the products of the reaction. The total yields of the identified heterocyclic compounds are 0.0023 percent. It is concluded that adenine synthesis occurs at a much lower concentration of hydrogen cyanide than has been shown by earlier studies. Pathways for the synthesis of purines from hydrogen cyanide are discussed, and a comparison of the heterocyclic compounds that have been identified in meteorites and in prebiotic reactions is presented.

  15. Modelling Action Potential Generation and Propagation in Fibroblastic Cells

    NASA Astrophysics Data System (ADS)

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

    2003-04-01

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

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

    PubMed

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

    2009-12-01

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

  17. 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.

  18. Near Discharge Cathode Assembly Plasma Potential Measurements in a 30-cm NSTAR Type Ion Engine During Beam Extraction

    NASA Technical Reports Server (NTRS)

    Herman, Daniel A.; Gallimore, Alec D.

    2006-01-01

    Floating emissive probe plasma potential data are presented over a two-dimensional array of locations in the near Discharge Cathode Assembly (DCA) region of a 30-cm diameter ring-cusp ion thruster. Discharge plasma data are presented with beam extraction at throttling conditions comparable to the NASA TH Levels 8, 12, and 15. The operating conditions of the Extended Life Test (ELT) of the Deep Space One (DS1) flight spare ion engine, where anomalous discharge keeper erosion occurred, were TH 8 and TH 12 consequently they are of specific interest in investigating discharge keeper erosion phenomena. The data do not validate the presence of a potential hill plasma structure downstream of the DCA, which has been proposed as a possible erosion mechanism. The data are comparable in magnitude to data taken by other researchers in ring-cusp electron-bombardment ion thrusters. The plasma potential structures are insensitive to thruster throttling level with a minimum as low as 14 V measured at the DCA exit plane and increasing gradually in the axial direction. A sharp increase in plasma potential to the bulk discharge value of 26 to 28 volts, roughly 10 mm radially from DCA centerline, was observed. Plasma potential measurements indicate a low-potential plume structure that is roughly 20 mm in diameter emanating from the discharge cathode that may be attributed to a free-standing plasma double layer.

  19. 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. PMID:9797043

  20. Multi-Model Assessment of Global Hydropower and Cooling Water Discharge Potential Under Climate Change

    NASA Technical Reports Server (NTRS)

    van Vliet, M. T. H.; van Beek, L. P. H.; Eisener, S.; Wada, Y.; Bierkens, M. F. P.

    2016-01-01

    Worldwide, 98% of total electricity is currently produced by thermoelectric power and hydropower. Climate change is expected to directly impact electricity supply, in terms of both water availability for hydropower generation and cooling water usage for thermoelectric power. Improved understanding of how climate change may impact the availability and temperature of water resources is therefore of major importance. Here we use a multi-model ensemble to show the potential impacts of climate change on global hydropower and cooling water discharge potential. For the first time, combined projections of streamflow and water temperature were produced with three global hydrological models (GHMs) to account for uncertainties in the structure and parametrization of these GHMs in both water availability and water temperature. The GHMs were forced with bias-corrected output of five general circulation models (GCMs) for both the lowest and highest representative concentration pathways (RCP2.6 and RCP8.5). The ensemble projections of streamflow and water temperature were then used to quantify impacts on gross hydropower potential and cooling water discharge capacity of rivers worldwide. We show that global gross hydropower potential is expected to increase between +2.4% (GCM-GHM ensemble mean for RCP 2.6) and +6.3% (RCP 8.5) for the 2080s compared to 1971-2000. The strongest increases in hydropower potential are expected for Central Africa, India, central Asia and the northern high-latitudes, with 18-33% of the world population living in these areas by the 2080s. Global mean cooling water discharge capacity is projected to decrease by 4.5-15% (2080s). The largest reductions are found for the United States, Europe, eastern Asia, and southern parts of South America, Africa and Australia, where strong water temperature increases are projected combined with reductions in mean annual streamflow. These regions are expected to affect 11-14% (for RCP2.6 and the shared socioeconomic

  1. Psychiatrists' duties in discharging sicker and potentially violent inpatients in the managed care era.

    PubMed

    Simon, R I

    1998-01-01

    Psychiatrists have certain clinical responsibilities and legal duties to patients treated in managed care settings. They include disclosure of all treatment options, the exercise of rights of appeal for any care they believe will materially benefit patients regardless of allocation guidelines or gatekeeper directives, continuance of emergency treatment, and reasonable cooperation with utilization reviewers. An additional duty--to warn and protect endangered third parties--will likely increase as cost-containment measures curtail the length of hospitalization. The author discusses these duties in the context of sicker and potentially violent patients. He cautions psychiatrists to be careful not to prematurely discharge these patients because of pressures from managed care organizations. The policies of such organizations can place psychiatrists and patients in a precarious position by limiting the time and resources for diagnosis and the assessment of the risk of potential violence. These responsibilities and duties often can be turned into clinical opportunities that enhance the therapeutic alliance with patients.

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

    PubMed Central

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

    2013-01-01

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

  3. A Critical Role for Neurofascin in Regulating Action Potential Initiation through Maintenance of the Axon Initial Segment

    PubMed Central

    Zonta, Barbara; Desmazieres, Anne; Rinaldi, Arianna; Tait, Steven; Sherman, Diane L.; Nolan, Matthew F.; Brophy, Peter J.

    2011-01-01

    Summary The axon initial segment (AIS) is critical for the initiation and propagation of action potentials. Assembly of the AIS requires interactions between scaffolding molecules and voltage-gated sodium channels, but the molecular mechanisms that stabilize the AIS are poorly understood. The neuronal isoform of Neurofascin, Nfasc186, clusters voltage-gated sodium channels at nodes of Ranvier in myelinated nerves: here, we investigate its role in AIS assembly and stabilization. Inactivation of the Nfasc gene in cerebellar Purkinje cells of adult mice causes rapid loss of Nfasc186 from the AIS but not from nodes of Ranvier. This causes AIS disintegration, impairment of motor learning and the abolition of the spontaneous tonic discharge typical of Purkinje cells. Nevertheless, action potentials with a modified waveform can still be evoked and basic motor abilities remain intact. We propose that Nfasc186 optimizes communication between mature neurons by anchoring the key elements of the adult AIS complex. PMID:21382554

  4. Action potentials from ventricular mechanoreceptors stimulated by occlusion of the coronary sinus in the dog

    PubMed Central

    Muers, M. F.; Sleight, P.

    1972-01-01

    1. In experiments to determine the type of intra-cardiac receptors which cause the coronary sinus occlusion reflex, recordings were made from sixty-nine single and small multi-fibre preparations of cardiac vagal afferents in open-chest anaesthetized dogs. 2. Thirty-two fibres were stimulated by occlusion of the coronary sinus outflow through an indwelling Morawitz cannula. No receptors were stimulated during occlusions at peak systolic coronary venous pressures below the threshold for reflex cardiovascular depression. At higher pressures, fibre recruitment and further increases in stimulated discharge were demonstrated. 3. The afferent endings of twenty-nine of these fibres were mechanically localized to the epicardium and myocardium of the left ventricle. Three were in the right ventricle. Seventeen single fibres discharged spontaneously at an average of 0·9 impulses/sec. There was cardiac modulation of both resting and stimulated discharge, with most action potentials in systole. Seven of eight fibres conducted at less than 1·0 m/sec. 4. These ventricular receptors and a further twenty-two otherwise like them but not stimulated by occlusions were designated epi-myocardial receptors. 5. 73% of receptors were stimulated by intrapericardial nicotine (50-100 μg). Presumptively superficial receptors were more sensitive to this stimulus. 6. Epi-myocardial receptors were stimulated by intravenous or intracoronary catecholamines, by electrical stimulation of cardiac sympathetic nerves, and by eliciting the carotid sinus occlusion reflex. Aortic occlusion stimulated 66% of fibres tested, but was a less effective stimulus. After all these stimuli, there was a systolic modulation of discharge in more than 70% of fibres. 7. It was concluded that the epi-myocardial receptors are similar to those previously shown to cause the epicardial chemoreflex, and to participate in the coronary chemoreflex. It is suggested that they are responsive to systolic mechanical changes which

  5. Performance analysis of stationary and discrete wavelet transform for action potential detection from sympathetic nerve recordings in humans.

    PubMed

    Salmanpour, Aryan; Brown, Lyndon J; Shoemaker, J Kevin

    2008-01-01

    Accurate investigation of the sympathetic nervous system is important in the diagnosis and study of various autonomic and cardiovascular control and disorders. Sympathetic function associated with blood pressure regulation in humans can be evaluated by recording muscle sympathetic nerve activity (MSNA), which is characterised by synchronous neuronal discharges separated by periods of neural silence dominated by colored gaussian noise. In this paper two common methods for detecting filtered action potential in MSNA recordings is compared. These methods are based on stationary wavelet transform (SWT) and discrete wavelet transform (DWT). The performance analysis are evaluated using simulated MSNA using templates extracted from real MSNA recorded from three healthy subjects.

  6. Mathematical model of the neonatal mouse ventricular action potential

    PubMed Central

    Wang, Linda J.; Sobie, Eric A.

    2008-01-01

    Therapies for heart disease are based largely on our understanding of the adult myocardium. The dramatic differences in action potential (AP) shape between neonatal and adult cardiac myocytes, however, indicate that a different set of molecular interactions in neonatal myocytes necessitates different treatment for newborns. Computational modeling is useful for synthesizing data to determine how interactions between components lead to systems-level behavior, but this technique has not been used extensively to study neonatal heart cell function. We created a mathematical model of the neonatal (day 1) mouse myocyte by modifying, based on experimental data, the densities and/or formulations of ion transport mechanisms in an adult cell model. The new model reproduces the characteristic AP shape of neonatal cells, with a brief plateau phase and longer duration than the adult (APD80=60.1 vs. 12.6 ms). The simulation results are consistent with experimental data, including: 1) decreased density, and altered inactivation, of transient outward K+ currents, 2) increased delayed rectifier K+ currents, 3) Ca2+ entry through T-type as well as L-type Ca2+ channels, 4) increased Ca2+ influx through Na+-Ca2+ exchange, and 5) Ca2+ transients resulting from transmembrane Ca2+ entry rather than release from the sarcoplasmic reticulum (SR). Simulations performed with the model generated novel predictions, including increased SR Ca2+ leak and elevated intracellular [Na+] in neonatal compared with adult myocytes. This new model can therefore be used for testing hypotheses and obtaining a better quantitative understanding of differences between neonatal and adult physiology. PMID:18408122

  7. Groundwater discharge: potential association with fecal indicator bacteria in the surf zone.

    PubMed

    Boehm, Alexandria B; Shellenbarger, Gregory G; Paytan, Adina

    2004-07-01

    Short-lived radium isotopes (223Ra and 224Ra) are used to investigate the potential association between groundwater discharge and microbial pollution at Huntington Beach, CA. We establish the tidally driven exchange of groundwater from the surficial beach aquifer across the beach face. Groundwater is found to be a source of nutrients (silica, inorganic nitrogen, and orthophosphate) to the surf zone, and these nutrients could possibly provide an environment for enhanced growth or increased persistence of fecal indicator bacteria (FIB). Ammonium and ortho-phosphate explain up to 12-20% of the variance in FIB levels in the surf zone. Elevated levels of FIB were only found in 1 of the 26 groundwater samples. However, FIB in the surf zone covary with radium at fortnightly, diurnal, and semi-diurnal tidal periods. In addition, radium accounts for up to 38% of the variance in log-FIB levels in the surf zone. A column experiment illustrates that Enterococcus suspended in Huntington Beach saline groundwater is not significantly filtered by sand collected from the field. This work establishes a mechanism for the subterranean delivery of FIB pollution to the surf zone from the surficial aquifer and presents evidence that supports an association between groundwater discharge and FIB.

  8. Influence of Wastewater Discharge on the Metabolic Potential of the Microbial Community in River Sediments.

    PubMed

    Li, Dong; Sharp, Jonathan O; Drewes, Jörg E

    2016-01-01

    To reveal the variation of microbial community functions during water filtration process in river sediments, which has been utilized widely in natural water treatment systems, this study investigates the influence of municipal wastewater discharge to streams on the phylotype and metabolic potential of the microbiome in upstream and particularly various depths of downstream river sediments. Cluster analyses based on both microbial phylogenetic and functional data collectively revealed that shallow upstream sediments grouped with those from deeper subsurface downstream regions. These sediment samples were distinct from those found in shallow downstream sediments. Functional genes associated with carbohydrate, xenobiotic, and certain amino acid metabolisms were overrepresented in upstream and deep downstream samples. In contrast, the more immediate contact with wastewater discharge in shallow downstream samples resulted in an increase in the relative abundance of genes associated with nitrogen, sulfur, purine and pyrimidine metabolisms, as well as restriction-modification systems. More diverse bacterial phyla were associated with upstream and deep downstream sediments, mainly including Actinobacteria, Planctomycetes, and Firmicutes. In contrast, in shallow downstream sediments, genera affiliated with Betaproteobacteria and Gammaproteobacteria were enriched with putative functions that included ammonia and sulfur oxidation, polyphosphate accumulation, and methylotrophic bacteria. Collectively, these results highlight the enhanced capabilities of microbial communities residing in deeper stream sediments for the transformation of water contaminants and thus provide a foundation for better design of natural water treatment systems to further improve the removal of contaminants.

  9. Potential ecological risks of thermal-treated waste recombination DNA discharged into an aquatic environment.

    PubMed

    Fu, Xiao H; Wang, Lei; Li, Meng N; Zeng, Xiao F; Le, Yi Q

    2011-01-01

    It has been shown that thermal-treatment at 100 ° C can denature deoxyribonucleic acid (DNA), yet this does not cause it to break down completely. To clarify the risk of gene pollution from thermal-treated recombinant DNA, the renaturation characteristics of thermal-denatured plasmid pET-28b and its persistence in aquatic environments were investigated. The results revealed that the double-stranded structure and transforming activity of the thermal-treated plasmid DNA could be recovered even if the thermal-treatment was conducted at 120 ° C. The presence of sodium chloride (NaCl) and ethylenediamine tetraacetic acid (EDTA) led to the increase of renaturation efficiency of the denatured DNA. When thermal-treated plasmid DNA was discharged into simulated aquatic environments with pH values from 5 to 9, it showed a longer persistence at pH 7 and 8 than that at 5, 6 and 9; however, the denatured plasmid DNA could persist for more than 33 min at any pH. Moreover, a higher ionic strength further protected the thermal-denatured plasmids from degradation in the simulated aquatic environment. These results indicated that when the thermal-treated DNA was discharged into an aquatic environment, it might not break down completely in a short period. Therefore, there is the potential for the discarded DNA to renature and transform, which might result in gene pollution.

  10. Heavy ion beam probe measurements of radial potential profiles in the modified Penning discharge

    NASA Technical Reports Server (NTRS)

    Kambic, G. X.

    1974-01-01

    A heavy ion beam probe was used to examine the radial potential profile of a plasma in the modified Penning discharge. The plasma has strong (approximately kV) electrostatic potentials near the anode ring which can be a large fraction of the injected ion beam energy. A primary (singly ionized) thallium ion beam is injected through the plasma in the midplane of a double Penning anode ring. After passage through the plasma, primary and secondary (doubly ionized) ions are detected with either a set of flat probes or an electrostatic energy analyzer. A calculation of the primary orbit through the plasma is performed to obtain an approximation to the measured primary beam trajectory. As the real radial potential profile is unknown, an adjustable model is used in the computer program. The adjustable potential profile is varied until the best agreement between measured and calculated trajectories is obtained. Secondary orbits are also predicted using the best fitting adjustable profile. The calculations indicate that secondary beams originating at more than one point in the plasma can be simultaneously observed at the electrostatic analyzer with certain primary beam initial conditions.

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

    NASA Astrophysics Data System (ADS)

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

    2013-12-01

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

  12. 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.

  13. 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

  14. 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,…

  15. Effect of a prenylamine analog (MG8926) on spontaneous action potentials in isolated rabbit sinoatrial node.

    PubMed

    Nakanishi, H; Matsuoka, I; Ono, T; Yoshida, H; Uchibori, T; Kogi, K

    1996-12-01

    Effects of verapamil, prenylamine and a prenylamine analog, MG8926 on the intracellular spontaneous action potentials recorded from the isolated rabbit sinoatrial (SA) node were studied. Verapamil (1 microM), a selective inhibitor for slow Ca2+ channels, prolonged the cycle length, decreased the rate of diastolic depolarization, the rate of rise of action potential, the amplitude of action potential and the maximal diastolic potential, and usually arrested showing subthreshold fluctuation of the membrane potential within several ten min. Prenylamine (10 microM), a nonselective inhibitor for slow Ca2+ channels, tended to prolong the cycle length to decrease the diastolic depolarization, the rate of rise of action potential, the amplitude of action potential. However, these changes were statistically insignificant. Prenylamine at the concentration of 10 microM had no effect on the maximal diastolic potential. MG8926 (10 microM) prolonged the cycle length, decreased the rate of diastolic depolarization, the rate of rise of action potential and tended to decrease the amplitude of action potential. MG8926 at the concentration of 10 microM had almost no effect on the maximal diastolic potential. The present findings may indicate that replacement of phenyl residue of prenylamine by cyclohexyl residue increases the inhibitory action on the slow Ca2+ channels in rabbit SA node.

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

    PubMed

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

    2012-01-10

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

  17. Mechanisms of action and potential therapeutic uses of thalidomide.

    PubMed

    Mujagić, Hamza; Chabner, Bruce A; Mujagić, Zlata

    2002-06-01

    Thalidomide was first introduced to the market in Germany under the brand name of Contergan in 1956, as a non-barbiturate hypnotic, advocated to ensure a good nights sleep and to prevent morning sickness in pregnancy. It was advertised for its prompt action, lack of hangover, and apparent safety. It has been banned from the market since 1963 after it caused the worldwide teratogenic disaster: babies exposed to thalidomide in utero during the first 34-50 days of pregnancy were born with severe life-threatening birth defects. Despite its unfortunate history, thalidomide has attracted scientific interest again because of its recently discovered action against inflammatory diseases and cancer. Its broad range of biological activities stems from its ability to moderate cytokine action in cancer and inflammatory diseases. Early studies examined its anxiolytic, mild hypnotic, antiemetic, and adjuvant analgesic properties. Subsequently, thalidomide was found to be highly effective in managing the cutaneous manifestations of leprosy, being superior to Aspirin in controlling leprosy-associated fever. Recent research has shown promising results with thalidomide in patients with myeloma, myelodysplastic syndrome, a variety of infectious diseases, autoimmune diseases, cancer, and progressive body weight loss related to advanced cancer and AIDS. Here we review the history of its development, pharmacokinetics, metabolism, biologic effects, and the results of clinical trials conducted thus far. Further research in this field should be directed towards better understanding of thalidomide metabolism, its mechanism of action, and the development of less toxic and more active analogs. PMID:12035132

  18. Mechanisms of action and potential therapeutic uses of thalidomide.

    PubMed

    Mujagić, Hamza; Chabner, Bruce A; Mujagić, Zlata

    2002-06-01

    Thalidomide was first introduced to the market in Germany under the brand name of Contergan in 1956, as a non-barbiturate hypnotic, advocated to ensure a good nights sleep and to prevent morning sickness in pregnancy. It was advertised for its prompt action, lack of hangover, and apparent safety. It has been banned from the market since 1963 after it caused the worldwide teratogenic disaster: babies exposed to thalidomide in utero during the first 34-50 days of pregnancy were born with severe life-threatening birth defects. Despite its unfortunate history, thalidomide has attracted scientific interest again because of its recently discovered action against inflammatory diseases and cancer. Its broad range of biological activities stems from its ability to moderate cytokine action in cancer and inflammatory diseases. Early studies examined its anxiolytic, mild hypnotic, antiemetic, and adjuvant analgesic properties. Subsequently, thalidomide was found to be highly effective in managing the cutaneous manifestations of leprosy, being superior to Aspirin in controlling leprosy-associated fever. Recent research has shown promising results with thalidomide in patients with myeloma, myelodysplastic syndrome, a variety of infectious diseases, autoimmune diseases, cancer, and progressive body weight loss related to advanced cancer and AIDS. Here we review the history of its development, pharmacokinetics, metabolism, biologic effects, and the results of clinical trials conducted thus far. Further research in this field should be directed towards better understanding of thalidomide metabolism, its mechanism of action, and the development of less toxic and more active analogs.

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

    ERIC Educational Resources Information Center

    Kitano, Margie K.

    2003-01-01

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

  20. Corrective Action Investigation Plan for Corrective Action Unit 262: Area 25 Septic Systems and Underground Discharge Point, Nevada Test Site, Nevada, Revision No. 1 (9/2001)

    SciTech Connect

    NNSA /NV

    2000-07-20

    This corrective action investigation plan contains the U.S. Department of Energy, Nevada Operations Office's approach to collect data necessary to evaluate corrective action alternatives appropriate for the closure of Corrective Action Unit (CAU) 262 under the Federal Facility Agreement and Consent Order. Corrective Action Unit 262 consists of nine Corrective Action Sites (CASs): Underground Storage Tank (25-02-06), Septic Systems A and B (25-04-06), Septic System (25-04-07), Leachfield (25-05-03), Leachfield (25-05-05), Leachfield (25-05-06), Radioactive Leachfield (25-05-08), Leachfield (25-05-12), and Dry Well (25-51-01). Situated in Area 25 at the Nevada Test Site (NTS), sites addressed by CAU 262 are located at the Reactor-Maintenance, Assembly, and Disassembly (R-MAD); Test Cell C; and Engine-Maintenance, Assembly, and Disassembly (E-MAD) facilities. The R-MAD, Test Cell C, and E-MAD facilities supported nuclear rocket reactor and engine testing as part of the Nuclear Rocket Development Station. The activities associated with the testing program were conducted between 1958 and 1973. Based on site history collected to support the Data Quality Objectives process, contaminants of potential concern (COPCs) for the site include oil/diesel-range total petroleum hydrocarbons, volatile organic compounds, semivolatile organic compounds, polychlorinated biphenyls, Resource Conservation and Recovery Act metals, and gamma-emitting radionuclides, isotopic uranium, isotopic plutonium, strontium-90, and tritium. The scope of the corrective action field investigation at the CAU will include the inspection of portions of the collection systems, sampling the contents of collection system features in situ of leachfield logging materials, surface soil sampling, collection of samples of soil underlying the base of inlet and outfall ends of septic tanks and outfall ends of diversion structures and distribution boxes, collection of soil samples from biased or a combination of

  1. 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.

  2. 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

  3. 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

  4. Differential action for ethanol on baroreceptor reflex control of heart rate and sympathetic efferent discharge in rats

    SciTech Connect

    Xin, Z.; Abdel-Rahman, A.R.A.; Wooles, W.R.

    1988-01-01

    The acute effects of ethanol (0.33, 0.66, or 1 g/kg) on baroreflex control of heart rate (HR) and sympathetic efferent discharge (SED) were investigated in rats. The two higher doses of ethanol caused a progressive and significant increase in baseline SED and a slight increase in HR. The findings suggest that the sensitivity of the reflex control of SED was preserved whereas that of HR was impaired after acute ethanol administration. Since these findings were obtained in the same animals, the data suggest that acute ethanol has a differential action on reflex control of SED and HR. Further, the significant increase in SED after moderate and high doses of ethanol suggests an increased central sympathetic tone as recordings were made from preganglionic nerve fibers (splanchnic nerve). The absence of an increase in baseline MAP, in spite of a significant increase in baseline SED following acute ethanol injection, could be explained, at least in part, by an ethanol-evoked reduction in pressor responsiveness to phenylephrine, an ..cap alpha..-adrenergic agonist.

  5. Discharge forecasting using MODIS and radar altimetry: potential application for transboundary flood risk management in Niger-Benue River basin

    NASA Astrophysics Data System (ADS)

    Tarpanelli, Angelica; Amarnath, Giriraj; Brocca, Luca; Moramarco, Tommaso

    2016-04-01

    Flooding is one of most widespread natural disasters in the world. Its impact is particularly severe and destructive in Asia and Africa, because the living conditions of some settlements are inadequate to cope with this type of natural hazard. In this context, the estimation of discharge is extremely important to address water management and flood risk assessment. However, the inadequate monitoring network hampers any control and prediction activity that could improve these disastrous situations. In the last few years, remote sensing sensors have demonstrated their effectiveness in retrieving river discharge, especially in supporting discharge nowcasting and forecasting activities. Recently, the potential of radar altimetry was apparent when used for estimating water levels in an ungauged river site with good accuracy. It has also become a very useful tool for estimation and prediction of river discharge. However, the low temporal resolution of radar altimeter observations (10 or 35 days, depending on the satellite mission) may be not suitable for day-by-day hydrological forecasting. Differently, MODerate resolution Imaging Spectroradiometer (MODIS), considering its proven potential for quantifying the variations in discharge of the rivers at daily time resolution may be more suited to this end. For these reasons, MODIS and radar altimetry data were used in this study to predicting and forecasting the river discharge along the Niger-Benue River, where severe flooding with extensive damage to property and loss of lives occurred. Therefore, an effective method to forecast flooding can support efforts towards creating an early warning system. In order to estimate river discharge, four MODIS products (daily, 8-day, and from AQUA and TERRA satellites) connected at three sites (two gauged and one ungauged) were used. The capability of remote sensing sensors to forecast discharge a few days in advance at a downstream section using MODIS and ENVISAT radar altimetry data

  6. Potential public health risks related to mercury/amalgam discharge from dental offices.

    PubMed

    Rowe, N H; Sidhu, K S; Chadzynski, L; Babcock, R F

    1996-02-01

    Mercury is a toxic and bioaccumulative metal. It exists in elemental, inorganic and organic forms. The use of mercury by the dental profession represents approximately 6 percent of the total annual domestic consumption and is estimated to contribute significantly to the discharge of mercury (14 percent in one study) to waste-water streams. Publicly owned treatment works (POTW) must obtain and comply with a National Pollutant Discharge Elimination System waste-water discharge permit. When minimal mercury discharge limits into surface waters are exceeded, an upstream search for contributors of mercury to the waste stream may result. Given the present sociopolitical environment, mercury discharge from dental offices will increasingly receive scrutiny. Strategies to minimize discharge of mercury/amalgam waste include engineering controls such as changes in the discharge process, changes in the composition of commercial products, and changes in control equipment. Governmental strategies include an outright ban, the setting of discharge standards, and educational efforts. Study of these strategies with evaluation of effectiveness is needed. PMID:9520646

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

    PubMed

    Rodriguez-Falces, Javier

    2015-03-01

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

  8. Corticospinal neurons in macaque ventral premotor cortex with mirror properties: a potential mechanism for action suppression?

    PubMed

    Kraskov, Alexander; Dancause, Numa; Quallo, Marsha M; Shepherd, Samantha; Lemon, Roger N

    2009-12-24

    The discovery of "mirror neurons" in area F5 of the ventral premotor cortex has prompted many theories as to their possible function. However, the identity of mirror neurons remains unknown. Here, we investigated whether identified pyramidal tract neurons (PTNs) in area F5 of two adult macaques exhibited "mirror-like" activity. About half of the 64 PTNs tested showed significant modulation of their activity while monkeys observed precision grip of an object carried out by an experimenter, with somewhat fewer showing modulation during precision grip without an object or grasping concealed from the monkey. Therefore, mirror-like activity can be transmitted directly to the spinal cord via PTNs. A novel finding is that many PTNs (17/64) showed complete suppression of discharge during action observation, while firing actively when the monkey grasped food rewards. We speculate that this suppression of PTN discharge might be involved in the inhibition of self-movement during action observation.

  9. Potential of pulsed corona discharges generated in water for the degradation of persistent pharmaceutical residues.

    PubMed

    Banaschik, Robert; Lukes, Petr; Jablonowski, Helena; Hammer, Malte U; Weltmann, Klaus-Dieter; Kolb, Juergen F

    2015-11-01

    Anthropogenic pollutants and in particular pharmaceutical residues are a potential risk for potable water where they are found in increasing concentrations. Different environmental effects could already be linked to the presence of pharmaceuticals in surface waters even for low concentrations. Many pharmaceuticals withstand conventional water treatment technologies. Consequently, there is a need for new water purification techniques. Advanced oxidation processes (AOP), and especially plasmas with their ability to create reactive species directly in water, may offer a promising solution. We developed a plasma reactor with a coaxial geometry to generate large volume corona discharges directly in water and investigated the degradation of seven recalcitrant pharmaceuticals (carbamazepine, diatrizoate, diazepam, diclofenac, ibuprofen, 17α-ethinylestradiol, trimethoprim). For most substances we observed decomposition rates from 45% to 99% for treatment times of 15-66 min. Especially ethinylestradiol and diclofenac were readily decomposed. As an inherent advantage of the method, we found no acidification and only an insignificant increase in nitrate/nitrite concentrations below legal limits for the treatment. Studies on the basic plasma chemical processes for the model system of phenol showed that the degradation is primarily caused by hydroxyl radicals. PMID:26218466

  10. Potential of turbidity monitoring for real time control of pollutant discharge in sewers during rainfall events.

    PubMed

    Lacour, C; Joannis, C; Gromaire, M-C; Chebbo, G

    2009-01-01

    Turbidity sensors can be used to continuously monitor the evolution of pollutant mass discharge. For two sites within the Paris combined sewer system, continuous turbidity, conductivity and flow data were recorded at one-minute time intervals over a one-year period. This paper is intended to highlight the variability in turbidity dynamics during wet weather. For each storm event, turbidity response aspects were analysed through different classifications. The correlation between classification and common parameters, such as the antecedent dry weather period, total event volume per impervious hectare and both the mean and maximum hydraulic flow for each event, was also studied. Moreover, the dynamics of flow and turbidity signals were compared at the event scale. No simple relation between turbidity responses, hydraulic flow dynamics and the chosen parameters was derived from this effort. Knowledge of turbidity dynamics could therefore potentially improve wet weather management, especially when using pollution-based real-time control (P-RTC) since turbidity contains information not included in hydraulic flow dynamics and not readily predictable from such dynamics.

  11. Potential of pulsed corona discharges generated in water for the degradation of persistent pharmaceutical residues.

    PubMed

    Banaschik, Robert; Lukes, Petr; Jablonowski, Helena; Hammer, Malte U; Weltmann, Klaus-Dieter; Kolb, Juergen F

    2015-11-01

    Anthropogenic pollutants and in particular pharmaceutical residues are a potential risk for potable water where they are found in increasing concentrations. Different environmental effects could already be linked to the presence of pharmaceuticals in surface waters even for low concentrations. Many pharmaceuticals withstand conventional water treatment technologies. Consequently, there is a need for new water purification techniques. Advanced oxidation processes (AOP), and especially plasmas with their ability to create reactive species directly in water, may offer a promising solution. We developed a plasma reactor with a coaxial geometry to generate large volume corona discharges directly in water and investigated the degradation of seven recalcitrant pharmaceuticals (carbamazepine, diatrizoate, diazepam, diclofenac, ibuprofen, 17α-ethinylestradiol, trimethoprim). For most substances we observed decomposition rates from 45% to 99% for treatment times of 15-66 min. Especially ethinylestradiol and diclofenac were readily decomposed. As an inherent advantage of the method, we found no acidification and only an insignificant increase in nitrate/nitrite concentrations below legal limits for the treatment. Studies on the basic plasma chemical processes for the model system of phenol showed that the degradation is primarily caused by hydroxyl radicals.

  12. Telling stories from everyday practice, an opportunity to see a bigger picture: a participatory action research project about developing discharge planning.

    PubMed

    Petersson, Pia; Springett, Jane; Blomqvist, Kerstin

    2009-11-01

    In spite of laws, rules and routines, findings from Swedish as well as international research show that discharge planning is not a simple matter. There is considerable knowledge about discharge planning, but the quality of the actual process in practice remains poor. With this in mind, a research and developmental health and social care network decided to use participation action research to explore the discharge planning situation in order to generate new ideas for development. This paper reports on the research process and the findings about our enhanced understanding about the discharge planning situation. Story dialogue method was used. The method is based on stories from everyday practice. The stories are used as 'triggers' to ask probing questions in a dialog and structured form. Local theory is developed to help the participants to find solutions for action in the practice. Our findings were that the discharge planning situation could be seen as a system including three interconnected areas: patient participation, practitioners' competence and organizational support. To reach good quality in discharge planning, all these three issues need to be developed, but not only as routines and forms. Rather, when developing a discharge planning situation, a system where relational aspects such as confidence and continuity are essential and thus needs to be considered. To achieve a change, the core problem needs to be clarified. When the issue is complex, the solution needs to consider the bigger picture and not just the parts. Telling stories from everyday practice, and to systematically reflect and analyse those in interprofessional groups can create opportunities for enhanced understanding, as well as be a vehicle for future change of practice.

  13. 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.

  14. 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

  15. 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

  16. Mastectomy - discharge

    MedlinePlus

    Breast removal surgery - discharge; Nipple-sparing mastectomy - discharge; Total mastectomy - discharge; Simple mastectomy - discharge; Modified radical mastectomy - discharge; Breast cancer - mastectomy -discharge

  17. Evaluation of the potentials of humic acid removal in water by gas phase surface discharge plasma.

    PubMed

    Wang, Tiecheng; Qu, Guangzhou; Ren, Jingyu; Yan, Qiuhe; Sun, Qiuhong; Liang, Dongli; Hu, Shibin

    2016-02-01

    Degradation of humic acid (HA), a predominant type of natural organic matter in ground water and surface waters, was conducted using a gas phase surface discharge plasma system. HA standard and two surface waters (Wetland, and Weihe River) were selected as the targets. The experimental results showed that about 90.9% of standard HA was smoothly removed within 40 min's discharge plasma treatment at discharge voltage 23.0 kV, and the removal process fitted the first-order kinetic model. Roles of some active species in HA removal were studied by evaluating the effects of solution pH and OH radical scavenger; and the results presented that O3 and OH radical played significant roles in HA removal. Scanning electron microscope (SEM) and FTIR analysis showed that HA surface topography and molecular structure were changed during discharge plasma process. The mineralization of HA was analyzed by UV-Vis spectrum, dissolved organic carbon (DOC), specific UV absorbance (SUVA), UV absorption ratios, and excitation-emission matrix (EEM) fluorescence. The formation of disinfection by-products during HA sample chlorination was also identified, and CHCl3 was detected as the main disinfection by-product, but discharge plasma treatment could suppress its formation to a certain extent. In addition, approximately 82.3% and 67.9% of UV254 were removed for the Weihe River water and the Wetland water after 40 min of discharge plasma treatment.

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

    PubMed

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

    2014-01-01

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

  19. Potential synergy of phytochemicals in cancer prevention: mechanism of action.

    PubMed

    Liu, Rui Hai

    2004-12-01

    Epidemiological studies have consistently shown that regular consumption of fruits and vegetables is strongly associated with reduced risk of developing chronic diseases, such as cancer and cardiovascular disease. It is now widely believed that the actions of the antioxidant nutrients alone do not explain the observed health benefits of diets rich in fruits and vegetables, because taken alone, the individual antioxidants studied in clinical trials do not appear to have consistent preventive effects. Work performed by our group and others has shown that fruits and vegetable phytochemical extracts exhibit strong antioxidant and antiproliferative activities and that the major part of total antioxidant activity is from the combination of phytochemicals. We proposed that the additive and synergistic effects of phytochemicals in fruits and vegetables are responsible for these potent antioxidant and anticancer activities and that the benefit of a diet rich in fruits and vegetables is attributed to the complex mixture of phytochemicals present in whole foods. This explains why no single antioxidant can replace the combination of natural phytochemicals in fruits and vegetables to achieve the health benefits. The evidence suggests that antioxidants or bioactive compounds are best acquired through whole-food consumption, not from expensive dietary supplements. We believe that a recommendation that consumers eat 5 to 10 servings of a wide variety of fruits and vegetables daily is an appropriate strategy for significantly reducing the risk of chronic diseases and to meet their nutrient requirements for optimum health.

  20. Metal speciation and potential bioavailability changes during discharge and neutralisation of acidic drainage water.

    PubMed

    Simpson, Stuart L; Vardanega, Christopher R; Jarolimek, Chad; Jolley, Dianne F; Angel, Brad M; Mosley, Luke M

    2014-05-01

    The discharge of acid drainage from the farm irrigation areas to the Murray River in South Australia represents a potential risk to water quality. The drainage waters have low pH (2.9-5.7), high acidity (up to 1190 mg L(-1) CaCO3), high dissolved organic carbon (10-40 mg L(-1)), and high dissolved Al, Co, Ni and Zn (up to 55, 1.25, 1.30 and 1.10 mg L(-1), respectively) that represent the greatest concern relative to water quality guidelines (WQGs). To provide information on bioavailability, changes in metal speciation were assessed during mixing experiments using filtration (colloidal metals) and Chelex-lability (free metal ions and weak inorganic metal complexes) methods. Following mixing of drainage and river water, much of the dissolved aluminium and iron precipitated. The concentrations of other metals generally decreased conservatively in proportion to the dilution initially, but longer mixing periods caused increased precipitation or adsorption to particulate phases. Dissolved Co, Mn and Zn were typically 95-100% present in Chelex-labile forms, whereas 40-70% of the dissolved nickel was Chelex-labile and the remaining non-labile fraction of dissolved nickel was associated with fine colloids or complexed by organic ligands that increased with time. Despite the different kinetics of precipitation, adsorption and complexation reactions, the dissolved metal concentrations were generally highly correlated for the pooled data sets, indicating that the major factors controlling the concentrations were similar for each metal (pH, dilution, and time following mixing). For dilutions of the drainage waters of less than 1% with Murray River water, none of the metals should exceed the WQGs. However, the high concentrations of metals associated with fine precipitates within the receiving waters may represent a risk to some aquatic organisms. PMID:24359925

  1. Identification and characterization of potential discharge areas for radionuclide transport by groundwater from a nuclear waste repository in Sweden.

    PubMed

    Berglund, Sten; Bosson, Emma; Selroos, Jan-Olof; Sassner, Mona

    2013-05-01

    This paper describes solute transport modeling carried out as a part of an assessment of the long-term radiological safety of a planned deep rock repository for spent nuclear fuel in Forsmark, Sweden. Specifically, it presents transport modeling performed to locate and describe discharge areas for groundwater potentially carrying radionuclides from the repository to the surface where man and the environment could be affected by the contamination. The modeling results show that topography to large extent determines the discharge locations. Present and future lake and wetland objects are central for the radionuclide transport and dose calculations in the safety assessment. Results of detailed transport modeling focusing on the regolith and the upper part of the rock indicate that the identification of discharge areas and objects considered in the safety assessment is robust in the sense that it does not change when a more detailed model representation is used.

  2. Terrestrial Sediment and Nutrient Discharge, and Their Potential Influence on Coral Reefs, Puerto Rico

    NASA Astrophysics Data System (ADS)

    Larsen, M. C.; Webb, R. M.; Warne, A. G.

    2004-12-01

    Sediment and nutrient discharge to the insular shelf of Puerto Rico (18 degrees latitude), augmented by anthropogenic activity, is believed to have contributed to widespread degradation of coral reefs of Puerto Rico during the 20th century. Sediment deposition degrades coral reefs because it reduces the area of sea floor suitable for growth of new coral, diminishes the amount of light available for photosynthesis by symbiotic algae that live within individual coral animals, and in extreme cases, buries coral colonies. Land-use history and data from 30 water-discharge, 9 daily and 15 intermittent sediment-concentration, and 24 water-quality gaging stations were analyzed to investigate the timing and intensity of terrestrial sediment and nutrient discharge into coastal waters. Watersheds in Puerto Rico generally are small (10's to 100's of square km), channel gradients are steep, and stream valleys are deeply incised and narrow. Major storms are usually brief (<24 h) but intense such that the majority of the annual sediment discharge occurs in a few days. From 1960 through 2000 the highest mean daily discharge for a water year (October - September) accounted for 20 to 60 percent of the total annual sediment discharge. Major storms, with a return frequency of approximately a decade, were capable of discharging up to 30 times the median annual sediment-discharge volume. Prior to agricultural and industrial development, coastal waters are believed to have been relatively transparent, with strong currents and seasonal high-energy swells assisting corals in the removal of minor amounts of sediment deposited after storms. Land clearing and modification, first for agriculture and later for urban development, have increased sediment and nutrient influx to the coast during the 19th and 20th centuries. Although forest cover has increased to approximately 30 percent of the surface of Puerto Rico during the past 60 years, sediment eroded from hillslopes during the agricultural

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

    PubMed Central

    Baccaglini, Paola I.; Spitzer, Nicholas C.

    1977-01-01

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

  4. Is action potential duration of the intact dog heart related to contractility or stimulus rate?

    PubMed

    Drake, A J; Noble, M I; Schouten, V; Seed, A; Ter Keurs, H E; Wohlfart, B

    1982-10-01

    1. The contractility (maximum rate of rise of left ventricular pressure) and action potential duration were measured in intact closed-chest anaesthetized dogs with complete atrioventricular dissociation and beta-adrenergic blockade.2. Measurements were confined to test beats following a 1 sec interval. Prior to the test interval (priming period) a variety of potentiating stimulus trains were introduced.3. When the frequency of stimulation was increased in the priming period (frequency potentiation), there was an inverse relationship between action potential duration and contractility of the test beat.4. When the test beat was potentiated by a single beat terminating the priming period with one short interval (post-extrasystolic potentiation), there was no relationship between the action potential duration and contractility of the test beat.5. Paired pulse stimulation was used for any given frequency to vary contractility by short interval potentiation. For any given frequency of stimulation there was no relationship between action potential duration and contractility of the test beat. For any given value of contractility, action potential duration decreased with increased frequency of stimulation.6. The introduction of a high frequency train caused a step decrease in action potential duration on the first beat of the train. This was followed by a further slow decline in action potential duration with a time course of over 3 min. These two changes could be dissociated by the introduction during the train of one second interval test pulses, which only showed the slow shortening.7. The lack of a consistent relationship between action potential duration and contractility of the test beat disagrees with the hypothesis that repolarization is controlled by the activator calcium responsible for the contractility. The action potential shortening associated with increased frequency is related to the frequency change per se.8. The slow time course of change in action

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2014-01-01

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

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

    PubMed

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

    2012-01-01

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

  8. Chloride current in mammalian cardiac myocytes. Novel mechanism for autonomic regulation of action potential duration and resting membrane potential

    PubMed Central

    1990-01-01

    The properties of the autonomically regulated chloride current (ICl) were studied in isolated guinea pig ventricular myocytes. This current was elicited upon exposure to isoproterenol (ISO) and reversed upon concurrent exposure to acetylcholine (ACh). ICl was time independent and exhibited outward rectification. The responses to ISO and ACh could be blocked by propranolol and atropine, respectively, and ICl was also elicited by forskolin, 8-bromoadenosine 3',5'-cyclic monophosphate, and 3-isobutyl-l-methylxanthine, indicating that the current is regulated through a cAMP-dependent pathway. The reversal potential of the ISO- induced current followed the predicted chloride equilibrium potential, consistent with it being carried predominantly by Cl-. Activation of ICl produced changes in the resting membrane potential and action potential duration, which were Cl- gradient dependent. These results indicate that under physiological conditions ICl may play an important role in regulating action potential duration and resting membrane potential in mammalian cardiac myocytes. PMID:2165130

  9. Addendum to the Corrective Action Decision Document/Closure Report for Corrective Action Unit 406: Area 3 Building 03-74 & Building 03-58 Underground Discharge Points and Corrective Action Unit 429: Area 3 Building 03-55 & Area 9 Building 09-52 Underground Discharge Points, Tonopah Test Range, Nevada, Revision 0

    SciTech Connect

    Lynn Kidman

    2008-10-01

    This document constitutes an addendum to the March 2000, Corrective Action Decision Document / Closure Report for Corrective Action Unit 406: Area 3 Building 03-74 & 03-58 Underground Discharge Points and Corrective Action Unit 429: Area 3 Building 03-55 & Area 9 Building 09-52 Underground Discharge Points (TTR) as described in the document Recommendations and Justifications for Modifications for Use Restrictions Established under the U.S. Department of Energy, National Nuclear Security Administration Nevada Site Office Federal Facility Agreement and Consent Order (UR Modification document) dated February 2008. The UR Modification document was approved by NDEP on February 26, 2008. The approval of the UR Modification document constituted approval of each of the recommended UR modifications. In conformance with the UR Modification document, this addendum consists of: • This cover page that refers the reader to the UR Modification document for additional information • The cover and signature pages of the UR Modification document • The NDEP approval letter • The corresponding section of the UR Modification document This addendum provides the documentation justifying the cancellation of the UR for CAS 03-51-001-0355 – Photo Shop UDP, Drains in CAU 429. It should be noted that there are no changes to CAU 406. This UR was established as part of a Federal Facility Agreement and Consent Order (FFACO) corrective action and is based on the presence of contaminants at concentrations greater than the action levels established at the time of the initial investigation (FFACO, 1996; as amended August 2006). Since this UR was established, practices and procedures relating to the implementation of risk-based corrective actions (RBCA) have changed. Therefore, this UR was re-evaluated against the current RBCA criteria as defined in the Industrial Sites Project Establishment of Final Action Levels (NNSA/NSO, 2006c). This re-evaluation consisted of comparing the original data

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

    NASA Astrophysics Data System (ADS)

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

    2016-03-01

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

  11. Distinct electrophysiological potentials for intention in action and prior intention for action.

    PubMed

    Vinding, Mikkel C; Jensen, Mads; Overgaard, Morten

    2014-01-01

    The role of conscious intention in relation to motoric movements has become a major topic of investigation in neuroscience. Traditionally, reports of conscious intention have been compared to various features of the readiness-potential (RP)--an electrophysiological signal that appears before voluntary movements. Experiments, however, tend to study intentions in immediate relation to movements (proximal intentions), thus ignoring other aspects of intentions such as planning or deciding in advance of movement (distal intentions). The current study examines the difference in electrophysiological activity between proximal intention and distal intention, using electroencephalography (EEG). Participants had to form an intention to move and then wait 2.5 sec before performing the actual movement. In this way, the electrophysiological activity related to forming a conscious intention was separated from any confounding activity related to automated motor activity. This was compared to conditions in which participants had to act as soon as they had the intention and a condition where participants acted upon an external cue 2.5 sec prior to movement. We examined the RP for the three conditions. No difference was found in early RP, but late RP differed significantly depending on the type of intention. In addition, we analysed signals during a longer time-interval starting before the time of distal intention formation until after the actual movement concluded. Results showed a slow negative electrophysiological "intention potential" above the mid-frontal areas at the time participants formed a distal intention. This potential was only found when the distal intention was self-paced and not when the intention was formed in response to an external cue.

  12. In-Stream Microbial Denitrification Potential at Wastewater Treatment Plant Discharge Sites

    NASA Astrophysics Data System (ADS)

    Hill, N. B.; Rahm, B. G.; Shaw, S. B.; Riha, S. J.

    2014-12-01

    Reactive nitrogen loading from municipal sewage discharge provides point sources of nitrate (NO3-) to rivers and streams. Through microbially-mediated denitrification, NO3- can be converted to dinitrogen (N2) and nitrous oxide (N2O) gases, which are released to the atmosphere. Preliminary observations made throughout summer 2011 near a wastewater treatment plant (WWTP) outfall in the Finger Lakes region of New York indicated that NO3- concentrations downstream of the discharge pipe were lower relative to upstream concentrations. This suggested that nitrate processing was occurring more rapidly and completely than predicted by current models and that point "sources" can in some cases be point "sinks". Molecular assays and stable isotope analyses were combined with laboratory microcosm experiments and water chemistry analyses to better understand the mechanism of nitrate transformation. Nitrite reductase (nirS and nirK) and nitrous oxide reductase (nosZ) genes were detected in water and sediment samples using qPCR. Denitrifcation genes were present attached to stream sediment, in pipe biofilm, and in WWTP discharge water. A comparison of δ18-O and δ15-N signatures also supported the hypothesis that stream NO3- had been processed biotically. Results from microcosm experiments indicated that the NO3- transformations occur at the sediment-water interface rather than in the water column. In some instances, quantities of denitrification genes were at higher concentrations attached to sediment downstream of the discharge pipe than upstream of the pipe suggesting that the wastewater discharge may be enriching the downstream sediment and could promote in-stream denitrification.

  13. Transient outward currents and action potential alterations in rabbit ventricular myocytes.

    PubMed

    Kawano, S; Hiraoka, M

    1991-06-01

    To clarify ionic mechanisms underlying successive changes in action potential repolarization upon sudden increase in driving rate or initiation of rapid drive after a rest, membrane potentials and currents were recorded from isolated rabbit ventricular myocytes using the suction-pipette whole-cell clamp method. When 20 action potentials were elicited with a stimulus frequency of 2.0 Hz after a rest period of 20 s, the plateau and action potential duration showed complex changes in successive beats, whereas they were nearly constant with stimulation at 0.1 Hz. There were only weak correlations between changes in action potential parameters and preceding diastolic intervals. The changes were prominent in the first 10 beats but subsided gradually thereafter, attaining nearly steady configurations of action potentials. When depolarizing pulses were applied at a fast rate, under the voltage clamp, the amplitudes of the initial inward current in the presence of tetrodotoxin changed greatly depending on the pulse numbers and diastolic intervals, whereas the delayed outward K+ current changed little. Variations of the initial inward current in successive pulses were caused by different degrees of activation and recovery from inactivation in the Ca2+ current, the Ca(2+)-sensitive and -insensitive transient outward current. While inhibition of either one or two current components decreased the action potential alterations, blocking the three components completely abolished them. These results indicate that alterations of the Ca(2+)-sensitive and -insensitive transient outward current together with the Ca2+ current contribute to the action potential alterations after initiation of rapid drive or an increase in driving rates.

  14. HF echoes from ionization potentially produced by high-altitude discharges

    SciTech Connect

    Roussel-Dupre, R.A.; Blanc, E.

    1997-03-01

    The presence of ionization associated with high-altitude discharges has been detected using an HF radar operating at 2.2, 2.5, and 2.8 MHz. On several occasions, oblique echoes lasting several hundred ms at night and 1{r_arrow}10s during the day were observed. The echoes turned on in several interpulse times of 70 ms and were generally correlated with strong lightning activity prior to onset. The angles of arrival of sferics detected at three goniometer stations were used to determine the distance to thunderstorms. The data are consistent with specular reflections from columns of ionization produced at 55{endash}65 km altitude and having minimum electron densities of 6{times}10{sup 4}{endash}10{sup 5}cm{sup {minus}3}. The source of the ionization is believed to be high-altitude discharges.{copyright} 1997 American Geophysical Union

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

    PubMed Central

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

    2016-01-01

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

  16. 16-Channel Organic Electrochemical Transistor Array for In Vitro Conduction Mapping of Cardiac Action Potential.

    PubMed

    Gu, Xi; Yao, Chunlei; Liu, Ying; Hsing, I-Ming

    2016-09-01

    16-Channel organic electrochemical transistor arrays (OECTs) are developed for mapping the propagation and studying the characteristics of action potentials of primary cardiomyocytes. The physiological activities of a rat cardiomyocyte monolayer during a long-term culturing is revealed by this biocompatible, low-cost, and high transconductance organic electronic device. OECT has great potential to be used in cardiac and neuronal drug screening.

  17. 7 CFR 1945.19 - Reporting potential natural disasters and initial actions.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 13 2012-01-01 2012-01-01 false Reporting potential natural disasters and initial... AGENCY, DEPARTMENT OF AGRICULTURE (CONTINUED) PROGRAM REGULATIONS (CONTINUED) EMERGENCY Disaster Assistance-General § 1945.19 Reporting potential natural disasters and initial actions. (a) Purpose....

  18. 7 CFR 1945.19 - Reporting potential natural disasters and initial actions.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 13 2011-01-01 2009-01-01 true Reporting potential natural disasters and initial... AGENCY, DEPARTMENT OF AGRICULTURE (CONTINUED) PROGRAM REGULATIONS (CONTINUED) EMERGENCY Disaster Assistance-General § 1945.19 Reporting potential natural disasters and initial actions. (a) Purpose....

  19. 7 CFR 1945.19 - Reporting potential natural disasters and initial actions.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 13 2010-01-01 2009-01-01 true Reporting potential natural disasters and initial... AGENCY, DEPARTMENT OF AGRICULTURE (CONTINUED) PROGRAM REGULATIONS (CONTINUED) EMERGENCY Disaster Assistance-General § 1945.19 Reporting potential natural disasters and initial actions. (a) Purpose....

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

    PubMed

    Marcotti, Walter; Johnson, Stuart L; Rusch, Alfons; Kros, Corne J

    2003-11-01

    Before the onset of hearing at postnatal day 12, mouse inner hair cells (IHCs) produce spontaneous and evoked action potentials. These spikes are likely to induce neurotransmitter release onto auditory nerve fibres. Since immature IHCs express both alpha1D (Cav1.3) Ca2+ and Na+ currents that activate near the resting potential, we examined whether these two conductances are involved in shaping the action potentials. Both had extremely rapid activation kinetics, followed by fast and complete voltage-dependent inactivation for the Na+ current, and slower, partially Ca2+-dependent inactivation for the Ca2+ current. Only the Ca2+ current is necessary for spontaneous and induced action potentials, and 29 % of cells lacked a Na+ current. The Na+ current does, however, shorten the time to reach the action-potential threshold, whereas the Ca2+ current is mainly involved, together with the K+ currents, in determining the speed and size of the spikes. Both currents increased in size up to the end of the first postnatal week. After this, the Ca2+ current reduced to about 30 % of its maximum size and persisted in mature IHCs. The Na+ current was downregulated around the onset of hearing, when the spiking is also known to disappear. Although the Na+ current was observed as early as embryonic day 16.5, its role in action-potential generation was only evident from just after birth, when the resting membrane potential became sufficiently negative to remove a sizeable fraction of the inactivation (half inactivation was at -71 mV). The size of both currents was positively correlated with the developmental change in action-potential frequency.

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

    PubMed Central

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

    2003-01-01

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

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

    PubMed

    Windeatt, Kirsten M; Handy, Richard D

    2013-06-01

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

  3. ATP-sensitive potassium channel modulation of the guinea pig ventricular action potential and contraction.

    PubMed

    Nichols, C G; Ripoll, C; Lederer, W J

    1991-01-01

    The role of ATP-sensitive potassium (KATP) channels in modulating the action potential and contraction of guinea pig ventricular myocytes was investigated. Under voltage clamp, the maximum whole-cell KATP channel conductance was estimated (195 +/- 10 nS, n = 6) by exposing the cells to complete metabolic blockade (2 mM cyanide in the presence of 10 mM 2-deoxy-glucose). In isolated inside-out membrane patches, the ATP dependence of KATP channel activity under relevant conditions was measured (half-maximal inhibition at 114 microM). Under current clamp (with intracellular ATP concentration = 5 mM), the effect of graded KATP channel activation on the action potential and the twitch was estimated by injection of a current (proportional to voltage) that simulated the KATP conductance. As this "conductance" was increased, the action potential was shortened, and contractile amplitude declined, as expected. From the results of these experiments, the quantitative dependence of the action potential duration on intracellular ATP concentration was estimated, without relying on a mathematical model of the cell membrane. The results imply that KATP-dependent action potential shortening is likely to occur if ATP concentration falls below normal levels (approximately 5 mM), as may happen regionally, or globally, during myocardial ischemia.

  4. [Potential for intervention of private health insurers in discharge management using the example of stroke patients].

    PubMed

    Sterl, E; Böhme, J

    2016-06-01

    The study reveals that stroke patients today can still experience gaps in the provision of healthcare and fragmented therapy. This is often the case on transferral from the inpatient to outpatient sector, causing complications that could be avoided by means of good discharge management across all sectors. Private health insurance can actively support and positively influence the treatment process in the form of case management. Individual contact with stroke patients and their relatives allows for early planning and organisation of the next steps, and offers patients the support they need during a difficult phase of life. PMID:27483688

  5. Action!

    ERIC Educational Resources Information Center

    Senese, Joseph

    1998-01-01

    A small group of teachers at one Illinois high school is helping to effect and promote change. Through the Action Research Laboratory (ARL), teams of teachers conduct collaborative action research to improve classroom practices. Data from the first two years of the ARL indicate that teachers are eager to participate in, and have thrived in, their…

  6. Evaluation of the potential of p-nitrophenol degradation in dredged sediment by pulsed discharge plasma.

    PubMed

    Wang, Tiecheng; Qu, Guangzhou; Sun, Qiuhong; Liang, Dongli; Hu, Shibin

    2015-11-01

    Hazardous pollutants in dredged sediment pose great threats to ecological environment and human health. A novel approach, named pulsed discharge plasma (PDP), was employed for the degradation of p-nitrophenol (PNP) in dredged sediment. Experimental results showed that 92.9% of PNP in sediment was smoothly removed in 60 min, and the degradation process fitted the first-order kinetic model. Roles of some active species in PNP degradation in sediment were studied by various gas plasmas, OH radical scavenger, hydrated electron scavenger and O2(·-) scavenger; and the results presented that O3, OH radical, eaq(-) and O2(·-) all played significant roles in PNP removal, and eaq(-) and O2(·-) mainly participated in other oxidising active species formation. FTIR analysis showed that PNP molecular structure was destroyed after PDP treatment. The main degradation intermediates were identified as hydroquinone, benzoquinone, phenol, acetic acid, NO2(-) and NO3(-). PNP degradation pathway in dredged sediment was proposed. It is expected to contribute to an alternative for sediment remediation by pulse discharge plasma. PMID:26207876

  7. Estimation of nearshore groundwater discharge and its potential effects on a fringing coral reef.

    PubMed

    Blanco, Ariel C; Watanabe, Atsushi; Nadaoka, Kazuo; Motooka, Shunsuke; Herrera, Eugene C; Yamamoto, Takahiro

    2011-04-01

    Radon (²²²Rn) measurements were conducted in Shiraho Reef (Okinawa, Japan) to investigate nearshore submarine groundwater discharge (SGD(nearshore)) dynamics. Estimated average groundwater flux was 2-3 cm/h (maximum 7-8 cm/h). End-member radon concentration and gas transfer coefficient were identified as major factors influencing flux estimation accuracy. For the 7-km long reef, SGD(nearshore) was 0.39-0.58 m³/s, less than 30% of Todoroki River's baseflow discharge. SGD(nearshore) was spatially and temporally variable, reflecting the strong influence of subsurface geology, tidal pumping, groundwater recharge, and hydraulic gradient. SGD(nearshore) elevated nearshore nitrate concentrations (0.8-2.2 mg/l) to half of Todoroki River's baseflow NO₃⁻-N (2-4 mg/L). This increased nearshore Chl-α from 0.5-2 μg/l compared to the typically low Chl-α (< 0.1-0.4 μg/l) in the moat. Diatoms and cyanobacteria concentrations exhibited an increasing trend. However, the percentage contributions of diatoms and cyanobacteria significantly decreased and increased, respectively. SGD may significantly induce the proliferation of cyanobacteria in nearshore reef areas.

  8. 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. PMID:25353835

  9. 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.

  10. 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.

  11. 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 %.

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

    PubMed

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

    2016-08-01

    Electrode designs and strategies for electroneurogram recordings are often tested first by computer simulations and then by animal models, but they are rarely implanted for long-term evaluation in humans. The models show that the amplitude of the potential at the surface of an axon is higher in front of the nodes of Ranvier than at the internodes; however, this has not been investigated through in vivo measurements. An original experimental method is presented to emulate a single fiber action potential in an infinite conductive volume, allowing the potential of an axon to be recorded at both the nodes of Ranvier and the internodes, for a wide range of electrode-to-fiber radial distances. The paper particularly investigates the differences in the action potential amplitude along the longitudinal axis of an axon. At a short radial distance, the action potential amplitude measured in front of a node of Ranvier is two times larger than in the middle of two nodes. Moreover, farther from the phantom axon, the measured action potential amplitude is almost constant along the longitudinal axis. The results of this new method confirm the computer simulations, with a correlation of 97.6 %. PMID:27016364

  13. Memantine reduces repetitive action potential firing in spinal cord nerve cell cultures.

    PubMed

    Netzer, R; Bigalke, H

    1990-09-21

    (1) The anticonvulsant effects of memantine were examined and compared with those of baclofen in monolayer primary cultures of murine nerve cells using conventional intracellular recordings. (2) Memantine and baclofen (each 10-100 microM) decreased spontaneous synaptic activity when action potential frequencies exceeded 6 Hz. Neurons firing action potentials at frequencies below 6 Hz (about 90% of all impaled cells), however, were not affected by the drugs. (3) Memantine reduced the duration of strychnine-elicited bursts and the firing rate of action potentials within a burst. In contrast, baclofen lowered the frequency of the bursts without reducing intra-burst firing. The duration of the bursts was increased. (4) Memantine, but not baclofen, reduced the extent of sustained repetitive firing evoked by pulses of depolarizing current. (5) In the presence of memantine, the second of two electrically evoked action potentials increasingly failed to appear as the intervals between successive stimulating pulses were shortened. Such an effect was not seen when baclofen was applied. Thus, both antispastic agents, memantine and baclofen, reduce hyperactivity of spinal cord neurons in culture, although their mechanisms of action are different.

  14. Assessing potential toxicity of chloride-affected groundwater discharging to an urban stream using juvenile freshwater mussels (Lampsilis siliquoidea).

    PubMed

    Roy, James W; McInnis, Rodney; Bickerton, Greg; Gillis, Patricia L

    2015-11-01

    Groundwater contaminants, such as chloride from road salt, pose a threat to aquatic ecosystems when and where they discharge to surface waters. Here we study the application of a laboratory toxicity bioassay to field-collected samples from contaminated groundwater discharging to an urban stream. The objectives were to assess the potential toxicity of the discharging groundwater, while also exploring the suitability of such standard tests to site groundwater. Juvenile freshwater mussels were chosen as a groundwater-appropriate (endobenthic) test organism. Groundwater was sampled from 6 sites at approximate depths of 0, 10, and 50 cm below the sediment. Concentrations of chloride and several metals were above aquatic life guidelines in some samples. Exposure (96-h) to site groundwater resulted in survival of 90-100% and 80-100% for the 0-cm and deeper samples, respectively, indicating that groundwater may pose a toxicological threat to freshwater mussels. Several samples with high chloride had a survival rate of 80%, but generally there was poor correlation between survival and individual contaminants. Parallel juvenile mussel exposures using reconstituted water and NaCl predicted survival in the natural groundwater below 50% based on chloride concentrations. This indicates some protective ability of groundwater, possibly associated with water hardness. Finally, some technical issues with performing bioassays with groundwater were noted. First, aeration of previously anoxic groundwater samples caused marked changes in water quality (especially metal concentrations). Second, calcite crystals formed on the mussel shells in samples with elevated chloride and water hardness, though with no apparent negative effects.

  15. Potentiation of the cytotoxic action of melphalan and "activated" cyclophosphamide against cultured tumor cells by centrophenoxine.

    PubMed

    Sladek, N E

    1977-01-01

    Centrophenoxine, without antitumor activity itself, enhanced the cytotoxic action of melphalan and "activated" cyclophosphamide against mouse P388 lymphoma and rat W256 carcinosarcoma cells growing in static suspension culture. The concentration of alkylating agent required for 99% cell-kill was approximately halved when centrophenoxine was also present during exposure to the antitumor drug. Maximum potentiation by centrophenoxine of the cytotoxic action of melphalan occurred when cells were exposed to the two agents simultaneously; little or no potentiation was observed when cells were exposed to centrophenoxine before or after exposure to the alkylating agent.

  16. Influence of the temperature of electrode material on its disintegration under the action of an arc discharge in hydrogen

    NASA Technical Reports Server (NTRS)

    Bolotov, A. V.; Yukhimchuk, S. A.

    1985-01-01

    An analysis is made of the electrophysical processes occurring at the end surface of rod electrodes during constant and alternating arc discharge in hydrogen. Experiments are reported on the effect of surface temperature of tungsten electrodes on their erosion. The influence of activating additions of thorium oxide, the structure of the tungsten, and the gas surrounding the electrode on the specific thermal loading and the erosion of the electrodes is discussed.

  17. The Study of Complex (Ti, Zr, Cs) Nanopowder Influencing the Effective Ionization Potential of Arc Discharge When Mma Welding

    NASA Astrophysics Data System (ADS)

    Sapozhkov, S. B.; Burakova, E. M.

    2016-08-01

    Strength is one of the most important characteristics of a weld joint. Mechanical properties of a weld metal can be improved in a variety of ways. One of the possibilities is to add a nanopowder to the weld metal. Authors of the paper suggest changing the production process of MMA welding electrodes via adding nanopowder Ti, Zr, Cs to electrode components through liquid glass. Theoretical research into the nanopowder influence on the effective ionization potential (Ueff) of welding arc discharge is also necessitated. These measures support arcing stability, improve strength of a weld joint, as the consequence, ensure quality enhancing of a weld joint and the structure on the whole.

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-01-01

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

  20. 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

  1. 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.

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

    PubMed

    Belz, Regina G

    2016-01-01

    Parthenin is a metabolite of Parthenium hysterophorus and is believed to contribute to the weed's invasiveness via allelopathy. Despite the potential of parthenin to suppress competitors, low doses stimulate plant growth. This biphasic action was hypothesized to be auxin-like and, therefore, an auxin-related mode of parthenin action was investigated using two approaches: joint action experiments with Lactuca sativa, and dose-response experiments with auxin/antiauxin-resistant Arabidopsis thaliana genotypes. The joint action approach comprised binary mixtures of subinhibitory doses of the auxin 3-indoleacetic acid (IAA) mixed with parthenin or one of three reference compounds [indole-3-butyric acid (IBA), 2,3,5-triiodobenzoic acid (TIBA), 2-(p-chlorophenoxy)-2-methylpropionic acid (PCIB)]. The reference compounds significantly interacted with IAA at all doses, but parthenin interacted only at low doses indicating that parthenin hormesis may be auxin-related, in contrast to its inhibitory action. The genetic approach investigated the response of four auxin/antiauxin-resistant mutants and a wildtype to parthenin or two reference compounds (IAA, PCIB). The responses of mutant plants to the reference compounds confirmed previous reports, but differed from the responses observed for parthenin. Parthenin stimulated and inhibited all mutants independent of resistance. This provided no indication for an auxin-related action of parthenin. Therefore, the hypothesis of an auxin-related inhibitory action of parthenin was rejected in two independent experimental approaches, while the hypothesis of an auxin-related stimulatory effect could not be rejected. PMID:26686984

  3. 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.

  4. 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…

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

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-19

    ... Federal Aviation Administration Potential Environmental Impacts of the Proposed Runway 13 Extension and... extension and associated actions for Devils Lake Regional Airport in Devils Lake, North Dakota. SUMMARY: The FAA has issued the final EA and FONSI/ROD for the proposed Runway 13 extension and associated...

  6. 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…

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

    NASA Astrophysics Data System (ADS)

    Decharms, R. Christopher; Merzenich, Michael M.

    1996-06-01

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

  8. Potential of electric discharge plasma methods in abatement of volatile organic compounds originating from the food industry.

    PubMed

    Preis, S; Klauson, D; Gregor, A

    2013-01-15

    Increased volatile organic compounds emissions and commensurate tightening of applicable legislation mean that the development and application of effective, cost-efficient abatement methods are areas of growing concern. This paper reviews the last two decades' publications on organic vapour emissions from food processing, their sources, impacts and treatment methods. An overview of the latest developments in conventional air treatment methods is presented, followed by the main focus of the paper, non-thermal plasma technology. The results of the review suggest that non-thermal plasma technology, in its pulsed corona discharge configuration, is an emerging treatment method with potential for low-cost, effective abatement of a wide spectrum of organic air pollutants. It is found that the combination of plasma treatment with catalysis is a development trend that demonstrates considerable potential. The as yet relatively small number of plasma treatment applications is considered to be due to the novelty of pulsed electric discharge techniques and a lack of reliable pulse generators and reactors. Other issues acting as barriers to widespread adoption of the technique include the possible formation of stable oxidation by-products, residual ozone and nitrogen oxides, and sensitivity towards air humidity.

  9. 'Catching the waves' - slow cortical potentials as moderator of voluntary action.

    PubMed

    Schmidt, Stefan; Jo, Han-Gue; Wittmann, Marc; Hinterberger, Thilo

    2016-09-01

    The readiness potential is an ongoing negativity in the EEG preceding a self-initiated movement by approximately 1.5s. So far it has predominantly been interpreted as a preparatory signal with a causal link to the upcoming movement. Here a different hypothesis is suggested which we call the selective slow cortical potential sampling hypothesis. In this review of recent research results we argue that the initiation of a voluntary action is more likely during negative fluctuations of the slow cortical potential and that the sampling and averaging of many trials leads to the observed negativity. That is, empirical evidence indicates that the early readiness potential is not a neural correlate of preconscious motor preparation and thus a determinant of action. Our hypothesis thereafter challenges the classic interpretation of the Libet experiment which is often taken as proof that there is no free will. We furthermore suggest that slow cortical potentials are related to an urge to act but are not a neural indicator of the decision process of action initiation. PMID:27328786

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

    NASA Astrophysics Data System (ADS)

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

    2016-05-01

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

  11. 'Catching the waves' - slow cortical potentials as moderator of voluntary action.

    PubMed

    Schmidt, Stefan; Jo, Han-Gue; Wittmann, Marc; Hinterberger, Thilo

    2016-09-01

    The readiness potential is an ongoing negativity in the EEG preceding a self-initiated movement by approximately 1.5s. So far it has predominantly been interpreted as a preparatory signal with a causal link to the upcoming movement. Here a different hypothesis is suggested which we call the selective slow cortical potential sampling hypothesis. In this review of recent research results we argue that the initiation of a voluntary action is more likely during negative fluctuations of the slow cortical potential and that the sampling and averaging of many trials leads to the observed negativity. That is, empirical evidence indicates that the early readiness potential is not a neural correlate of preconscious motor preparation and thus a determinant of action. Our hypothesis thereafter challenges the classic interpretation of the Libet experiment which is often taken as proof that there is no free will. We furthermore suggest that slow cortical potentials are related to an urge to act but are not a neural indicator of the decision process of action initiation.

  12. 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.

  13. 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.

  14. Effects of mexiletine on transmembrane action potentials as affected by external potassium concentration and by rate of stimulation in guinea-pig papillary muscles.

    PubMed

    Sada, H; Ban, T; Oshita, S

    1980-11-01

    1. The effects of mexiletine and quinidine were compared on transmembrane potentials in guinea-pig papillary muscles, using conventional microelectrode techniques. 2. Mexiletine (23.1 mumol/l) decreased the maximum rate of rise of the action potential (Vmax) and increased the ratio of the effective refractory period to the action potential duration at 90% repolarization level (ERP/APD90); these effects were prominent with elevation of the external potassium concentration ([K]o) from 2.7 to 5.4, 8.1 and 10.0 mmol/l. 3. The percentage decrease in Vmax induced by 5 and 10 mumol/l of quinidine was approximately constant in 2.7, 5.4 and 10.0 mmol/l [K]o solutions. 4. The decrease in Vmax produced by mexiletine was progressively increased as the driving rate was raised from 0.25 to 5Hz. This rate-dependent change was pronounced when the concentration was raised from 23.1 to 46.2 and 92.4 mumol/l. 5. Mexiletine in concentrations of 23.1 and 92.4 mumol/l delayed the recovery of Vmax in a premature action potential to the level of Vmax in the conditioning action potentials at the driving rate of 0.25 Hz. 6. It appears that mexiletine exerts its anti-arrhythmic action by a selective depressant effect on depolarized cells (high [K]0) and cells with high frequency discharges, as is the case with lignocaine.

  15. Nurses' Assessment of Rehabilitation Potential and Prediction of Functional Status at Discharge from Inpatient Rehabilitation

    ERIC Educational Resources Information Center

    Myers, Jamie S.; Grigsby, Jim; Teel, Cynthia S.; Kramer, Andrew M.

    2009-01-01

    The goals of this study were to evaluate the accuracy of nurses' predictions of rehabilitation potential in older adults admitted to inpatient rehabilitation facilities and to ascertain whether the addition of a measure of executive cognitive function would enhance predictive accuracy. Secondary analysis was performed on prospective data collected…

  16. An experimental study on a function of the cupula. Effect of cupula removal on the ampullary nerve action potential.

    PubMed

    Suzuki, M; Harada, Y; Sugata, Y

    1984-01-01

    We used a posterior semicircular canal that had been isolated from a frog. From the utricular side the ampulla was cut open at a position one third of the way along the long axis. The cupula was removed through this opening using a glass micropipette. The action potential from the posterior ampullary nerve was recorded before and after removal of the cupula. After removal, the action potential disappeared almost completely. When the cupula was put back on the crista, the action potential was restored. When the cupula was put back upside down, the action potential recovered, but to a lesser extent.

  17. The mode of action of quinidine on isolated rabbit atria interpreted from intracellular potential records.

    PubMed

    VAUGHAN WILLIAMS, E M

    1958-09-01

    An attempt has been made to show why quinidine, which has long been known not to lengthen the duration of the cardiac action potential, measured with external electrodes, and also not to lengthen, and sometimes to shorten, the absolute refractory period, nevertheless reduces the maximum frequency at which atria can respond to a stimulus. Simultaneous measurements have been made in electrically driven isolated rabbit atria of contractions, conduction velocity and intracellular potentials before and during exposure to a wide range of concentrations of quinidine sulphate. The resting potential remained undiminished, in contrast to the effect of quinidine on Purkinje fibres. In the therapeutic range of doses, up to 10 mg./l., the half-time for repolarization was either shortened or unchanged, thus providing an explanation for the failure of quinidine to prolong the absolute refractory period. In contrast, even at low concentrations of quinidine, conduction velocity and the rate of rise of the action potential were greatly slowed, and the height of the overshoot was reduced. The terminal phase of the action potential was prolonged. It is known that the rate of rise of the action potential is a function of the level of repolarization at which an impulse takes off (the more negative the take-off point, the faster the rate of rise). Normally, a stimulus introduced when repolarization has proceeded to 2/3 of the resting potential evokes a response with a rate of rise fast enough for propagation, so that the duration of the terminal 1/3 of the phase of repolarization has no influence upon the length of the effective refractory period. In the presence of quinidine, however, the rate of rise itself was directly reduced, thus repolarization had to proceed further before the critical take-off point was reached at which the rate of rise was fast enough for propagation, and the duration of the terminal phase of repolarization thus became significant. It has been concluded that

  18. Direction of action potential propagation influences calcium increases in distal dendrites of the cricket giant interneurons.

    PubMed

    Ogawa, Hiroto; Baba, Yoshichika; Oka, Kotaro

    2002-10-01

    To understand the relationship between the propagation direction of action potentials and dendritic Ca(2+) elevation, simultaneous measurements of intracellular Ca(2+) concentration ([Ca(2+)](i)) and intradendritic membrane potential were performed in the wind-sensitive giant interneurons of the cricket. The dendritic Ca(2+) transients induced by synaptically-evoked action potentials had larger amplitudes than those induced by backpropagating spikes evoked by antidromic stimulation. The amplitude of the [Ca(2+)](i) changes induced by antidromic stimuli combined with subthreshold synaptic stimulation was not different from that of the Ca(2+) increases evoked by the backpropagating spikes alone. This result means that the synaptically activated Ca(2+) release from intracellular stores does not contribute to enhancement of Ca(2+) elevation induced by backpropagating spikes. On the other hand, the synaptically evoked action potentials were also increased at distal dendrites in which the Ca(2+) elevation was enhanced. When the dendritic and axonal spikes were simultaneously recorded, the delay between dendritic spike and ascending axonal spike depended upon which side of the cercal nerves was stimulated. Further, dual intracellular recording at different dendritic branches illustrated that the dendritic spike at the branch arborizing on the stimulated side preceded the spike recorded at the other side of the dendrite. These results suggest that the spike-initiation site shifts depending on the location of the activated postsynaptic site. It is proposed that the difference of spike propagation manner could change the action potential waveform at the distal dendrite, and could produce synaptic activity-dependent Ca(2+) dynamics in the giant interneurons.

  19. Potential cost savings from discharge allowance trading: A case study and implications for water quality trading

    NASA Astrophysics Data System (ADS)

    Sado, Yukako; Boisvert, Richard N.; Poe, Gregory L.

    2010-02-01

    Applying a trading ratio system similar to that proposed by Hung and Shaw (2005), we estimate the potential cost savings of a phosphorus emissions trading program that meets overall total maximum daily load allocations among 22 wastewater treatment plants (WWTPs) in the Passaic River watershed (United States) to be a modest 2-3% relative to a no-trade baseline. These results may be typical of those in relatively small watersheds such as the Passaic, where there are limited numbers of potential traders and relatively homogeneous abatement technologies across WWTPs. More substantial gains from trade may accrue to a concentrated group of WWTPs, suggesting that watershed managers should focus on a targeted set of traders within a watershed. Under certain conditions, additional gains may be achieved by aggregating WWTPs into zones within which there can be one-to-one allowance trading.

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

    PubMed

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

    2012-03-01

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

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

    PubMed

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

    2012-03-01

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

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

    PubMed

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

    2015-10-01

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

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

    PubMed Central

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

    2014-01-01

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

  4. Post-tetanic mechanical tension and evoked action potentials in McArdle's disease

    PubMed Central

    Brandt, N. J.; Buchthal, F.; Ebbesen, F.; Kamieniecka, Z.; Krarup, C.

    1977-01-01

    The tension produced by the cramp evoked in the adductor pollicis muscle by repetitive stimuli to the nerve (20/s for 50 s) and by full voluntary effort in the brachial biceps was measured in a patient with McArdle's disease. The contracture was 17% of the peaktetanic tension, and was not associated with action potentials. Twitches superimposed on the contracture were at most diminished to half, as were their action potentials. Both slow and fast muscle fibres participated in the contracture. The contraction time of the twitches elicited after the tetanus was prolonged more in the patient than in a normal subject of the same age. There was evidence of delayed firing, first observed 90 seconds after the peak of the contracture. The patient had electromyographic and histological signs of myopathy. PMID:271684

  5. 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

  6. Attention-dependent reductions in burstiness and action potential height in macaque area V4

    PubMed Central

    Anderson, Emily B.; Mitchell, Jude F.; Reynolds, John H.

    2013-01-01

    Attention improves the encoding of visual stimuli. One mechanism that is implicated in facilitating sensory encoding is the firing of action potentials in bursts. We tested the hypothesis that when spatial attention is directed to a stimulus, this causes an increase in burst firing to the attended stimulus. To the contrary, we found an attention-dependent reduction in burstiness among putative pyramidal neurons in macaque area V4. We accounted for this using a conductance-based Hodgkin-Huxley style model in which attentional modulation stems from scaling excitation and inhibition. The model exhibited attention-dependent increases in firing rate and made the surprising and correct prediction that when attention is directed into a neuron’s receptive field, this reduces action potential height. The model thus provided a unified explanation for three distinct forms of attentional modulation, two of them novel, and implicates scaling of the responses of excitatory and inhibitory input populations in mediating attention. PMID:23852114

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

    PubMed Central

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

    2015-01-01

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

  8. 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

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

    PubMed

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

    2016-05-01

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

  10. Action potential wavelength restitution predicts alternans and arrhythmia in murine Scn5a+/− hearts

    PubMed Central

    Matthews, Gareth D K; Guzadhur, Laila; Sabir, Ian N; Grace, Andrew A; Huang, Christopher L-H

    2013-01-01

    Reductions in cardiac action potential wavelength, and the consequent wavebreak, have been implicated in arrhythmogenesis. Tachyarrhythmias are more common in the Brugada syndrome, particularly following pharmacological challenge, previously modelled using Scn5a+/− murine hearts. Propagation latencies and action potential durations (APDs) from monophasic action potential recordings were used to assess wavelength changes with heart rate in Langendorff-perfused wild-type (WT) and Scn5a+/− hearts. Recordings were obtained from right (RV) and left (LV) ventricular, epicardial and endocardial surfaces during incremental pacing, before and following flecainide or quinidine challenge. Conduction velocities (θ′), action potential wavelengths (λ′= APD ×θ′), and their corresponding alternans depended non-linearly upon diastolic interval (DI). Maximum θ′ was lower in Scn5a+/− RV epicardium than endocardium. Flecainide further reduced θ′, accentuating this RV conduction block. Quinidine reduced maximum θ′ in WT and caused earlier conduction failure in the RV of both Scn5a+/− and WT. Use of recovery wavelengths (λ′0= DI ×θ′) rather than DI, provided novel λ restitution plots of λ′ against λ′0, which sum to a basic cycle distance permitting feedback analysis. λ′ restitution gradient better correlated with alternans magnitude than either APD or θ restitution gradient. The large differences in θ′ and APD restitution contrasted with minor differences in maximum λ′ between epi- and endocardia of untreated hearts, and quinidine-treated WT hearts. Strikingly, all regions and conditions converged to a common instability point, implying a conserved relationship. Flecainide or quinidine decreased the pacing rates at which this occurred, through reducing basic cycle distance, in the Scn5a+/− RV epicardium, directly predictive of its arrhythmic phenotype. PMID:23836691

  11. Compound action potentials recorded in the human spinal cord during neurostimulation for pain relief.

    PubMed

    Parker, John L; Karantonis, Dean M; Single, Peter S; Obradovic, Milan; Cousins, Michael J

    2012-03-01

    Electrical stimulation of the spinal cord provides effective pain relief to hundreds of thousands of chronic neuropathic pain sufferers. The therapy involves implantation of an electrode array into the epidural space of the subject and then stimulation of the dorsal column with electrical pulses. The stimulation depolarises axons and generates propagating action potentials that interfere with the perception of pain. Despite the long-term clinical experience with spinal cord stimulation, the mechanism of action is not understood, and no direct evidence of the properties of neurons being stimulated has been presented. Here we report novel measurements of evoked compound action potentials from the spinal cords of patients undergoing stimulation for pain relief. The results reveal that Aβ sensory nerve fibres are recruited at therapeutic stimulation levels and the Aβ potential amplitude correlates with the degree of coverage of the painful area. Aβ-evoked responses are not measurable below a threshold stimulation level, and their amplitude increases with increasing stimulation current. At high currents, additional late responses are observed. Our results contribute towards efforts to define the mechanism of spinal cord stimulation. The minimally invasive recording technique we have developed provides data previously obtained only through microelectrode techniques in spinal cords of animals. Our observations also allow the development of systems that use neuronal recording in a feedback loop to control neurostimulation on a continuous basis and deliver more effective pain relief. This is one of numerous benefits that in vivo electrophysiological recording can bring to a broad range of neuromodulation therapies. PMID:22188868

  12. Noisy unmaskers of multistability of periodic rhythms in a model of the ventricular cardiac action potential

    NASA Astrophysics Data System (ADS)

    Surovyatkina, Elena; Egorchenkov, Roman; Ivanov, Guennady

    2007-06-01

    The coexistence of different dynamical regimes of cardiac cell-model at a fixed set of stimulation parameters, i.e. multistability, revealed by noise is presented in this paper. Numerical simulations are performed using Luo-Rudy (LR1) action potential model. Numerical experiments with LR1 model conducted via noisy periodical stimulation showed the coexistence of several periodic rhythms. Weak noise in period of stimulation causes a hopping process between all the (meta-) stable rhythms of cell-model. This process is reflected in several parallel branches of the bifurcation diagram: noise unveils new, invisible before, stable rhythms which could appear in this model at different initial conditions. The phenomenon of multistability is directly evidenced by other numerical experiments: we have established the multistability property of a cell consisting in the fact that different initial conditions of stimulation (different extrasystole application times) lead to different stable periodic rhythms. We have obtained the shaping of attraction basins on the action potential curves. Such basins of attraction contain a set of initial conditions which determinate a stable periodic rhythm. We have found a close association between the attraction basins of the complex rhythms on the curves of action potential and the cardiac vulnerable windows on ECG record, during which extra stimuli can induce life threatening arrhythmias. Obtained results allow us to make a conclusion that multistability is very important for the electrical conduction system of the heart from the cell level to the integrated function of the heart.

  13. Seasonal variation in conduction velocity of action potentials in squid giant axons.

    PubMed

    Rosenthal, J J; Bezanilla, F

    2000-10-01

    To determine whether the electrical properties of the squid giant axon are seasonally acclimated, action potentials, recorded at different temperatures, were compared between giant axons isolated from Loligo pealei caught in May, from relatively cold waters (approximately 10 degrees-12 degrees C), and in August, from relatively warm waters (approximately 20 degrees C). Parameters relating to the duration of the action potential (e.g., maximum rate of rise, maximum rate of fall, and duration at half-peak) did not change seasonally. The relationship between conduction velocity and temperature remained constant between seasons as well, in spite of the fact that May axons were significantly larger than August axons. When normalized to the fiber diameter, mean May conduction velocities were 83% of the August values at all temperatures tested, and analysis of the rise time of the action potential foot suggested that a change in the axoplasmic resistivity was responsible for this difference. Direct measurements of axoplasmic resistance further supported this hypothesis. Thus seasonal changes in the giant axon's size and resistivity are not consistent with compensatory thermal acclimation, but instead serve to maintain a constant relationship between conduction velocity and temperature.

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

    PubMed

    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 (Ca(2+)) is one of the key regulators of cell survival and it can induce ER stress-mediated apoptosis in response to various conditions. Ca(2+) regulates cell death both at the early and late stages of apoptosis. Severe Ca(2+) dysregulation can promote cell death through apoptosis. Action potential, an electrical signal transmitted along the neurons and muscle fibers, is important for conveying information to, from, and within the brain. Upon the initiation of the action potential, increased levels of cytosolic Ca(2+) (depolarization) lead to the activation of the ER stress response involved in the initiation of apoptosis. In this review, we discuss the involvement of Ca(2+) and action potential in ER stress-mediated apoptosis. PMID:27649160

  15. 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

  16. The electrogenic Na+/HCO3− cotransport modulates resting membrane potential and action potential duration in cat ventricular myocytes

    PubMed Central

    Villa-Abrille, María C; Petroff, Martín G Vila; Aiello, Ernesto A

    2007-01-01

    Perforated whole-cell configuration of patch clamp was used to determine the contribution of the electrogenic Na+/HCO3− cotransport (NBC) on the shape of the action potential in cat ventricular myocytes. Switching from Hepes to HCO3− buffer at constant extracellular pH (pHo) hyperpolarized resting membrane potential (RMP) by 2.67 ± 0.42 mV (n = 9, P < 0.05). The duration of action potential measured at 50% of repolarization time (APD50) was 35.8 ± 6.8% shorter in the presence of HCO3− than in its absence (n = 9, P < 0.05). The anion blocker SITS prevented and reversed the HCO3−-induced hyperpolarization and shortening of APD. In addition, no HCO3−-induced hyperpolarization and APD shortening was observed in the absence of extracellular Na+. Quasi-steady-state currents were evoked by 8 s duration voltage-clamped ramps ranging from −130 to +30 mV. A novel component of SITS-sensitive current was observed in the presence of HCO3−. The HCO3−-sensitive current reversed at −87 ± 5 mV (n = 7), a value close to the expected reversal potential of an electrogenic Na+/HCO3− cotransport with a HCO3−:Na+ stoichiometry ratio of 2: 1. The above results allow us to conclude that the cardiac electrogenic Na+/HCO3− cotransport has a relevant influence on RMP and APD of cat ventricular cells. PMID:17138608

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

    PubMed

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

    2013-11-15

    Multi-electrode arrays (MEAs) can be used for noninvasive, real-time, and long-term recording of electrophysiological activity and changes in the extracellular chemical microenvironment. Neural network organization, neuronal excitability, synaptic and phenotypic plasticity, and drug responses may be monitored by MEAs, but it is still difficult to measure presynaptic activity, such as neurotransmitter release, from the presynaptic bouton. In this study, we describe the development of planar carbon nanotube (CNT)-MEA chips that can measure both the release of the neurotransmitter dopamine as well as electrophysiological responses such as field postsynaptic potentials (fPSPs) and action potentials (APs). These CNT-MEA chips were fabricated by electroplating the indium-tin oxide (ITO) microelectrode surfaces. The CNT-plated ITO electrode exhibited electrochemical response, having much higher current density compared with the bare ITO electrode. Chronoamperometric measurements using these CNT-MEA chips detected dopamine at nanomolar concentrations. By placing mouse striatal brain slices on the CNT-MEA chip, we successfully measured synaptic dopamine release from spontaneous firings with a high S/N ratio of 62. Furthermore, APs and fPSPs were measured from cultured hippocampal neurons and slices with high temporal resolution and a 100-fold greater S/N ratio. Our CNT-MEA chips made it possible to measure neurotransmitter dopamine (presynaptic activities), postsynaptic potentials, and action potentials, which have a central role in information processing in the neuronal network. CNT-MEA chips could prove useful for in vitro studies of stem cell differentiation, drug screening and toxicity, synaptic plasticity, and pathogenic processes involved in epilepsy, stroke, and neurodegenerative diseases. PMID:23774164

  18. 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.

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

    PubMed

    Desbois, Andrew P; Smith, Valerie J

    2010-02-01

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

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

    PubMed Central

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

    1992-01-01

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

  1. [Potential Bioavailability of Dissolved Organic Nitrogen in the Discharge Outlets of Sewage Treatment Plants Around the Jiaozhou Bay].

    PubMed

    Kong, Xiu-jun; Zhang, Peng; Yang, Nan-nan; Liang, Sheng-kang

    2016-03-15

    Dissolved organic nitrogen (DON) is an important portion of total dissolved nitrogen (TDN) transported to the coastal from land-based sources and its bioavailable moieties of DON are regarded as potentially important nitrogen sources for eutrophication in coastal environments. Based on the four field observations conducted in July, November 2012 and in March, May 2013 at the four sewage treatment plants (STPs) around the Jiaozhou Bay (JZB), the concentrations and compositions of total dissolved nitrogen (TDN) as well as total dissolved amino acids (TDAA) were analyzed, and the ratio of dissolved organic carbon (DOC) to DON and the composition and abundance of amino acids were regarded as indexes to evaluate the bioavailability of DON in STPs around JZB. The concentrations of TDN ranged from 413.10 µmol L⁻¹ to 3,580.65 µmol · L⁻¹ and showed a seasonal variation tendency, which were higher in March and November and lower in May and July, and the percentages of DON to TDN varied from 2.14% to 88.75%. In the discharge outlets of STPs around JZB, the values of DOC/DON were low and ranged from 0.2 mol · mol⁻¹ to 26.2 mol · mol⁻¹ with an average of (5.05 ± 6.39) mol · mol⁻¹, while the values of TDAA/DOC were high and ranged from 0.33% to 3.02% with an average of 1.54% ± 0.78%. Based on TDAA/DOC, the bioavailable proportion of the dissolved organic matter was estimated, which accounted for 0.44% to 46.97%. In conclusion, DON in the discharge outlets of STPs around JZB possessed high bioavailability and might contribute to the eutrophication of coastal water in JZB. PMID:27337875

  2. [Potential Bioavailability of Dissolved Organic Nitrogen in the Discharge Outlets of Sewage Treatment Plants Around the Jiaozhou Bay].

    PubMed

    Kong, Xiu-jun; Zhang, Peng; Yang, Nan-nan; Liang, Sheng-kang

    2016-03-15

    Dissolved organic nitrogen (DON) is an important portion of total dissolved nitrogen (TDN) transported to the coastal from land-based sources and its bioavailable moieties of DON are regarded as potentially important nitrogen sources for eutrophication in coastal environments. Based on the four field observations conducted in July, November 2012 and in March, May 2013 at the four sewage treatment plants (STPs) around the Jiaozhou Bay (JZB), the concentrations and compositions of total dissolved nitrogen (TDN) as well as total dissolved amino acids (TDAA) were analyzed, and the ratio of dissolved organic carbon (DOC) to DON and the composition and abundance of amino acids were regarded as indexes to evaluate the bioavailability of DON in STPs around JZB. The concentrations of TDN ranged from 413.10 µmol L⁻¹ to 3,580.65 µmol · L⁻¹ and showed a seasonal variation tendency, which were higher in March and November and lower in May and July, and the percentages of DON to TDN varied from 2.14% to 88.75%. In the discharge outlets of STPs around JZB, the values of DOC/DON were low and ranged from 0.2 mol · mol⁻¹ to 26.2 mol · mol⁻¹ with an average of (5.05 ± 6.39) mol · mol⁻¹, while the values of TDAA/DOC were high and ranged from 0.33% to 3.02% with an average of 1.54% ± 0.78%. Based on TDAA/DOC, the bioavailable proportion of the dissolved organic matter was estimated, which accounted for 0.44% to 46.97%. In conclusion, DON in the discharge outlets of STPs around JZB possessed high bioavailability and might contribute to the eutrophication of coastal water in JZB.

  3. 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.

  4. Ocean Thermal Energy Conversion: the potential impact on microphytoplankton of bottom water discharge at subsurface in the Caribbean Sea

    NASA Astrophysics Data System (ADS)

    Giraud, Mélanie; Boye, Marie; Garçon, Véronique; L'Helguen, Stéphane; Donval, Anne; De la Broise, Denis

    2015-04-01

    Part of the solar energy can be harvested and used in different processes. Taking advantage of the natural temperature gradient between the surface and deep ocean, the Ocean Thermal Energy Conversion (OTEC) process fulfills this goal. The IMPALA project (Impacts of artificial upwelling on microplankton) aims to study the potential environmental impacts of releasing, below the surface, deep seawater flowing out of a scheduled OTEC pilot plant offshore the Martinique Island in the Caribbean Sea. Biogeochemical processes involved in the artificial upwelling generated by the use of an Ocean Thermal Energy Conversion (OTEC) plant were studied in this poor nutrient environment. The biogeochemical and physical ecosystem structure and functioning on the OTEC site were described and deep seawater discharge using in situ microcosm experiments was carried out off Martinique. Surface seawater was collected in ultra-clean conditions at two depths (corresponding to the maximum of chlorophyll a concentration and bottom of nutricline) and mixed in different proportions with deep seawater (2% and 10%). Pigments determination, picophytoplankton abundance, macro-nutrients (silicates, nitrates, and phosphates), particular organic carbon and nitrogen concentrations and primary production were documented to assess the variability between the natural environment and within the microcosms. The latter were immersed for 6 days on a 250 meters mooring. Variations observed in microcosms experiments and in the surrounding waters were compared in order to evaluate the natural variability of the phytoplankton assemblage and the potential shifts induced by deep water supply. Results obtained during two fields campaigns conducted off Martinique at the onset of the dry (November-December 2013) and wet seasons (June 2014), respectively, will be presented and discussed. Incubating mixtures of subsurface and deep waters at two ratios and at two depths, allows evaluating the potential impact of a deep

  5. Xenin-25 Potentiates Glucose-dependent Insulinotropic Polypeptide Action via a Novel Cholinergic Relay Mechanism*

    PubMed Central

    Wice, Burton M.; Wang, Songyan; Crimmins, Dan L.; Diggs-Andrews, Kelly A.; Althage, Matthew C.; Ford, Eric L.; Tran, Hung; Ohlendorf, Matthew; Griest, Terry A.; Wang, Qiuling; Fisher, Simon J.; Ladenson, Jack H.; Polonsky, Kenneth S.

    2010-01-01

    The intestinal peptides GLP-1 and GIP potentiate glucose-mediated insulin release. Agents that increase GLP-1 action are effective therapies in type 2 diabetes mellitus (T2DM). However, GIP action is blunted in T2DM, and GIP-based therapies have not been developed. Thus, it is important to increase our understanding of the mechanisms of GIP action. We developed mice lacking GIP-producing K cells. Like humans with T2DM, “GIP/DT” animals exhibited a normal insulin secretory response to exogenous GLP-1 but a blunted response to GIP. Pharmacologic doses of xenin-25, another peptide produced by K cells, restored the GIP-mediated insulin secretory response and reduced hyperglycemia in GIP/DT mice. Xenin-25 alone had no effect. Studies with islets, insulin-producing cell lines, and perfused pancreata indicated xenin-25 does not enhance GIP-mediated insulin release by acting directly on the β-cell. The in vivo effects of xenin-25 to potentiate insulin release were inhibited by atropine sulfate and atropine methyl bromide but not by hexamethonium. Consistent with this, carbachol potentiated GIP-mediated insulin release from in situ perfused pancreata of GIP/DT mice. In vivo, xenin-25 did not activate c-fos expression in the hind brain or paraventricular nucleus of the hypothalamus indicating that central nervous system activation is not required. These data suggest that xenin-25 potentiates GIP-mediated insulin release by activating non-ganglionic cholinergic neurons that innervate the islets, presumably part of an enteric-neuronal-pancreatic pathway. Xenin-25, or molecules that increase acetylcholine receptor signaling in β-cells, may represent a novel approach to overcome GIP resistance and therefore treat humans with T2DM. PMID:20421298

  6. Xenin-25 potentiates glucose-dependent insulinotropic polypeptide action via a novel cholinergic relay mechanism.

    PubMed

    Wice, Burton M; Wang, Songyan; Crimmins, Dan L; Diggs-Andrews, Kelly A; Althage, Matthew C; Ford, Eric L; Tran, Hung; Ohlendorf, Matthew; Griest, Terry A; Wang, Qiuling; Fisher, Simon J; Ladenson, Jack H; Polonsky, Kenneth S

    2010-06-25

    The intestinal peptides GLP-1 and GIP potentiate glucose-mediated insulin release. Agents that increase GLP-1 action are effective therapies in type 2 diabetes mellitus (T2DM). However, GIP action is blunted in T2DM, and GIP-based therapies have not been developed. Thus, it is important to increase our understanding of the mechanisms of GIP action. We developed mice lacking GIP-producing K cells. Like humans with T2DM, "GIP/DT" animals exhibited a normal insulin secretory response to exogenous GLP-1 but a blunted response to GIP. Pharmacologic doses of xenin-25, another peptide produced by K cells, restored the GIP-mediated insulin secretory response and reduced hyperglycemia in GIP/DT mice. Xenin-25 alone had no effect. Studies with islets, insulin-producing cell lines, and perfused pancreata indicated xenin-25 does not enhance GIP-mediated insulin release by acting directly on the beta-cell. The in vivo effects of xenin-25 to potentiate insulin release were inhibited by atropine sulfate and atropine methyl bromide but not by hexamethonium. Consistent with this, carbachol potentiated GIP-mediated insulin release from in situ perfused pancreata of GIP/DT mice. In vivo, xenin-25 did not activate c-fos expression in the hind brain or paraventricular nucleus of the hypothalamus indicating that central nervous system activation is not required. These data suggest that xenin-25 potentiates GIP-mediated insulin release by activating non-ganglionic cholinergic neurons that innervate the islets, presumably part of an enteric-neuronal-pancreatic pathway. Xenin-25, or molecules that increase acetylcholine receptor signaling in beta-cells, may represent a novel approach to overcome GIP resistance and therefore treat humans with T2DM. PMID:20421298

  7. Phasic changes in intracellular pH during action potentials of sheep Purkinje fibres.

    PubMed

    Pressler, M L

    1988-01-01

    Regulation of intracellular pH (pHi) and the relationship between H+ and Ca2+ may vary during activity. Ion-selective microelectrodes were used to record pHi during action potentials of sheep Purkinje fibres prolonged by low temperature (21 degrees C) and elevated CO2 content. Intracellular pH also was measured during changes in extracellular calcium concentration, [Ca2+]o. Cytosolic alkalinization (peak pHi change, 0.03-0.05) was observed during the long action-potential plateau and transient acidification (0.01-0.02 units) upon repolarization. Potassium-induced depolarization to plateau potentials (i.e. to -15 +/- 2 mV) simulated the peak magnitude of the alkalinization. However, compensation for the alkalinization occurred at a faster rate during the action potential (8.9 +/- 4.3 nM/min) than during K+ depolarization (1.2 +/- 0.5 nM/min). In comparison, the cytoplasm acidified in resting fibres (0.06-0.07 log units) during changes of [Ca2+]o thought to increase intracellular calcium concentration. Alterations of pHi were translated into changes of proton concentration ([H+]i). Ten- to twenty-fold elevation of [Ca2+]o evoked a comparable change in [H+]i (mean increase, 5.7 nM) but oppositely directed from that during the plateau (mean decrease, 8.8 nM). The findings in resting fibres seem consistent with displacement of bound protons by Ca2+. In contrast, the initial change in pHi during the plateau is proposed to be consequent to Ca2+-release from sarcoplasmic reticulum and/or phosphocreatine hydrolysis coupled to ATP regeneration.

  8. Two-dimensional spatial survey of the plasma potential and electric field in a pulsed bipolar magnetron discharge

    SciTech Connect

    Vetushka, A.; Karkari, S.K.; Bradley, J.W.

    2004-11-01

    Emissive and Langmuir probe techniques have been used to obtain two-dimensional (2D) spatial maps of the plasma potential V{sub p}, electric field E, and ion trajectories in a pulsed bipolar magnetron discharge. The magnetron was pulsed at a frequency of 100 kHz, with a 50% duty cycle and operated at an argon pressure of 0.74 Pa. The pulse wave form was characterized by three distinct phases: the 'overshoot', 'reverse', and 'on' phases. In the 'on' phase of the pulse, when the cathode voltage is driven to -670 V, the 2D spatial distribution of V{sub p} has a similar form to that in dc magnetron, with significant axial and radial electric fields in the bulk plasma, accelerating ions to the sheath edge above the cathode racetrack region. During the 'overshoot' phase (duration 200 ns), V{sub p} is raised to values greater than +330 V, more than 100 V above the cathode potential, with E pointing away from the target. In the 'reverse' phase V{sub p} has a value of +45 V at all measured positions, 2 V more positive than the target potential. In this phase there is no electric field present in the plasma. In the bulk of the plasma, the results from Langmuir probe and the emissive probe are in good agreement, however, in one particular region of the plasma outside the radius of the cathode, the emissive probe measurements are consistently more positive (up to 45 V in the 'on' time). This discrepancy is discussed in terms of the different frequency response of the probes and their perturbation of the plasma. A simple circuit model of the plasma-probe system has been proposed to explain our results. A brief discussion of the effect of the changing plasma potential distribution on the operation of the magnetron is given.

  9. Addendum to the Closure Report for Corrective Action Unit 339: Area 12 Fleet Operations Steam Cleaning Discharge Area, Nevada Test Site, Revision 0

    SciTech Connect

    Grant Evenson

    2009-05-01

    This document constitutes an addendum to the Closure Report for CAU 339: Area 12 Fleet Operations Steam Cleaning Discharge Area Nevada Test Site, December 1997 as described in the document Supplemental Investigation Report for FFACO Use Restrictions, Nevada Test Site, Nevada (SIR) dated November 2008. The SIR document was approved by NDEP on December 5, 2008. The approval of the SIR document constituted approval of each of the recommended UR removals. In conformance with the SIR document, this addendum consists of: • This page that refers the reader to the SIR document for additional information • The cover, title, and signature pages of the SIR document • The NDEP approval letter • The corresponding section of the SIR document This addendum provides the documentation justifying the cancellation of the UR for CAS 12-19-01, A12 Fleet Ops Steam Cleaning Efflu. This UR was established as part of a Federal Facility Agreement and Consent Order (FFACO) corrective action and is based on the presence of contaminants at concentrations greater than the action levels established at the time of the initial investigation (FFACO, 1996). Since this UR was established, practices and procedures relating to the implementation of risk-based corrective actions (RBCA) have changed. Therefore, this UR was reevaluated against the current RBCA criteria as defined in the Industrial Sites Project Establishment of Final Action Levels (NNSA/NSO, 2006). This re-evaluation consisted of comparing the original data (used to define the need for the UR) to risk-based final action levels (FALs) developed using the current Industrial Sites RBCA process. The re-evaluation resulted in a recommendation to remove the UR because contamination is not present at the site above the risk-based FALs. Requirements for inspecting and maintaining this UR will be canceled, and the postings and signage at this site will be removed. Fencing and posting may be present at this site that are unrelated to the

  10. Pancreatitis - discharge

    MedlinePlus

    Chronic pancreatitis - discharge; Pancreatitis - chronic - discharge; Pancreatic insufficiency - discharge; Acute pancreatitis - discharge ... fluids through an intravenous (IV) tube in your vein and nutrition through a feeding tube or IV. ...

  11. Knee arthroscopy - discharge

    MedlinePlus

    ... retinacular release - discharge; Synovectomy - discharge; Patellar debridement - discharge; Meniscus repair - discharge; Lateral release - discharge; Collateral ligament repair - discharge; Knee surgery - ...

  12. Potential water-quality effects of coal-bed methane production water discharged along the upper Tongue River, Wyoming and Montana

    USGS Publications Warehouse

    Kinsey, Stacy M.; Nimick, David A.

    2011-01-01

    Water quality in the upper Tongue River from Monarch, Wyoming, downstream to just upstream from the Tongue River Reservoir in Montana potentially could be affected by discharge of coal-bed methane (CBM) production water (hereinafter referred to as CBM discharge). CBM discharge typically contains high concentrations of sodium and other ions that could increase dissolved-solids (salt) concentrations, specific conductance (SC), and sodium-adsorption ratio (SAR) in the river. Increased inputs of sodium and other ions have the potential to alter the river's suitability for agricultural irrigation and aquatic ecosystems. Data from two large tributaries, Goose Creek and Prairie Dog Creek, indicate that these tributaries were large contributors to the increase in SC and SAR in the Tongue River. However, water-quality data were not available for most of the smaller inflows, such as small tributaries, irrigation-return flows, and CBM discharges. Thus, effects of these inflows on the water quality of the Tongue River were not well documented. Effects of these small inflows might be subtle and difficult to determine without more extensive data collection to describe spatial patterns. Therefore, synoptic water-quality sampling trips were conducted in September 2005 and April 2006 to provide a spatially detailed profile of the downstream changes in water quality in this reach of the Tongue River. The purpose of this report is to describe these downstream changes in water quality and to estimate the potential water-quality effects of CBM discharge in the upper Tongue River. Specific conductance of the Tongue River through the study reach increased from 420 to 625 microsiemens per centimeter (.μS/cm; or 49 percent) in the downstream direction in September 2005 and from 373 to 543 .μS/cm (46 percent) in April 2006. Large increases (12 to 24 percent) were measured immediately downstream from Goose Creek and Prairie Dog Creek during both sampling trips. Increases attributed to

  13. 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

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

    PubMed

    Wu, J; Wikswo, J P

    1997-11-01

    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.

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

    NASA Astrophysics Data System (ADS)

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

    2014-05-01

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

  16. 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.

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

    PubMed

    Bridge, J H; Ershler, P R; Cannell, M B

    1999-07-15

    1. Calcium sparks were examined in enzymatically dissociated mouse cardiac ventricular cells using the calcium indicator fluo-3 and confocal microscopy. The properties of the mouse cardiac calcium spark are generally similar to those reported for other species. 2. Examination of the temporal relationship between the action potential and the time course of calcium spark production showed that calcium sparks are more likely to occur during the initial repolarization phase of the action potential. The latency of their occurrence varied by less than 1.4 ms (s.d.) and this low variability may be explained by the interaction of the gating of L-type calcium channels with the changes in driving force for calcium entry during the action potential. 3. When fixed sites within the cell are examined, calcium sparks have relatively constant amplitude but the amplitude of the sparks was variable among sites. The low variability of the amplitude of the calcium sparks suggests that more than one sarcoplasmic reticulum (SR) release channel must be involved in their genesis. Noise analysis (with the assumption of independent gating) suggests that > 18 SR calcium release channels may be involved in the generation of the calcium spark. At a fixed site, the response is close to 'all-or-none' behaviour which suggests that calcium sparks are indeed elementary events underlying cardiac excitation-contraction coupling. 4. A method for selecting spark sites for signal averaging is presented which allows the time course of the spark to be examined with high temporal and spatial resolution. Using this method we show the development of the calcium spark at high signal-to-noise levels.

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

    PubMed

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

    2015-08-11

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

  19. 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

  20. 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

  1. Stereotactic radiosurgery - discharge

    MedlinePlus

    Gamma knife - discharge; Cyberknife - discharge; Stereotactic radiotherapy - discharge; Fractionated stereotactic radiotherapy- discharge; Cyclotrons- discharge; Linear accelerator- discharge; Lineacs - discharge; Proton beam radiosurgery - discharge

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

    NASA Astrophysics Data System (ADS)

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

    2013-11-01

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

  3. Rapid local synchronization of action potentials: toward computation with coupled integrate-and-fire neurons.

    PubMed Central

    Hopfield, J J; Herz, A V

    1995-01-01

    The collective behavior of interconnected spiking nerve cells is investigated. It is shown that a variety of model systems exhibit the same short-time behavior and rapidly converge to (approximately) periodic firing patterns with locally synchronized action potentials. The dynamics of one model can be described by a downhill motion on an abstract energy landscape. Since an energy landscape makes it possible to understand and program computation done by an attractor network, the results will extend our understanding of collective computation from models based on a firing-rate description to biologically more realistic systems with integrate-and-fire neurons. Images Fig. 2 PMID:7624307

  4. Potential profile near singularity point in kinetic Tonks-Langmuir discharges as a function of the ion sources temperature

    NASA Astrophysics Data System (ADS)

    Kos, L.; Tskhakaya, D. D.; Jelić, N.

    2011-05-01

    A plasma-sheath transition analysis requires a reliable mathematical expression for the plasma potential profile Φ(x) near the sheath edge xs in the limit ɛ ≡λD/ℓ =0 (where λD is the Debye length and ℓ is a proper characteristic length of the discharge). Such expressions have been explicitly calculated for the fluid model and the singular (cold ion source) kinetic model, where exact analytic solutions for plasma equation (ɛ =0) are known, but not for the regular (warm ion source) kinetic model, where no analytic solution of the plasma equation has ever been obtained. For the latter case, Riemann [J. Phys. D: Appl. Phys. 24, 493 (1991)] only predicted a general formula assuming relatively high ion-source temperatures, i.e., much higher than the plasma-sheath potential drop. Riemann's formula, however, according to him, never was confirmed in explicit solutions of particular models (e.g., that of Bissell and Johnson [Phys. Fluids 30, 779 (1987)] and Scheuer and Emmert [Phys. Fluids 31, 3645 (1988)]) since "the accuracy of the classical solutions is not sufficient to analyze the sheath vicinity" [Riemann, in Proceedings of the 62nd Annual Gaseous Electronic Conference, APS Meeting Abstracts, Vol. 54 (APS, 2009)]. Therefore, for many years, there has been a need for explicit calculation that might confirm the Riemann's general formula regarding the potential profile at the sheath edge in the cases of regular very warm ion sources. Fortunately, now we are able to achieve a very high accuracy of results [see, e.g., Kos et al., Phys. Plasmas 16, 093503 (2009)]. We perform this task by using both the analytic and the numerical method with explicit Maxwellian and "water-bag" ion source velocity distributions. We find the potential profile near the plasma-sheath edge in the whole range of ion source temperatures of general interest to plasma physics, from zero to "practical infinity." While within limits of "very low" and "relatively high" ion source temperatures

  5. Actions taken in response to the potential for volatile organics in RLWTF influent tanks

    SciTech Connect

    DEL SIGNORE, JOHN C.

    2007-01-01

    Positive USQD-RL W -06.0729-JPS, titled "Potential for Volatile Organics in RLW" was signed Friday, 09-08-06, at 1600. It resulted from a Potentially Inadequate Safety Analysis (PISA) for the Radioactive Liquid Waste Treatment Facility (RLWTF) at Technical Area 50. The PISA posits that an unspecified accident occurs at a generator facility, and that said accident does not ignite the volatile organic liquid, but results instead in the release of a large volume of volatile organic liquid into an RLW drain. Once in the drain, the liquid flows unimpeded into the RLWTF influent tanks. After entering the influent tanks, a spark causes a deflagration or explosion. This report documents actions taken in response to the PISA.

  6. 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.

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

    PubMed

    Schlaepfer, Charles H; Wessel, Ralf

    2015-01-01

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

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

    PubMed

    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.

  9. The linear synchronization measures of uterine EMG signals: Evidence of synchronized action potentials during propagation.

    PubMed

    Domino, Malgorzata; Pawlinski, Bartosz; Gajewski, Zdzislaw

    2016-11-01

    Evaluation of synchronization between myoelectric signals can give new insights into the functioning of the complex system of porcine myometrium. We propose a model of uterine contractions according to the hypothesis of action potentials similarity which is possible to detect during propagation in the uterine wall. We introduce similarity measures based on the concept of synchronization as used in matching linear signals such as electromyographic (EMG) time series data. The aim was to present linear measures to assess synchronization between contractions in different topographic regions of the uterus. We use the cross-correlation function (ƒx,y[l], ƒy,z[l]) and the cross-coherence function (Cxy[ƒ], Cyz[ƒ]) to assess synchronization between three data series of a diestral uterine EMG bundles in porcine reproductive tract. Spontaneous uterine activity was recorded using telemetry method directly by three-channel transmitter and three silver bipolar needle electrodes sutured on different topographic regions of the reproductive tract in the sow. The results show the usefulness of the cross-coherence function in that synchronization between uterine horn and corpus uteri for multiple action potentials (bundles) could be observed. The EMG bundles synchronization may be used to investigate the direction and velocity of EMG signals propagation in porcine reproductive tract. PMID:27570104

  10. From damage response to action potentials: early evolution of neural and contractile modules in stem eukaryotes.

    PubMed

    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.

  11. 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

  12. 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

  13. Quantitative Assessment of the Distributions of Membrane Conductances Involved in Action Potential Backpropagation Along Basal Dendrites

    PubMed Central

    Acker, Corey D.; Antic, Srdjan D.

    2009-01-01

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

  14. Potential effects of groundwater pumping on water levels, phreatophytes, and spring discharges in Spring and Snake Valleys, White Pine County, Nevada, and adjacent areas in Nevada and Utah

    USGS Publications Warehouse

    Halford, Keith J.; Plume, Russell W.

    2011-01-01

    Fish Springs, and changes in discharge on selected creek reaches were measurement observations. The effects of uncertain distributed groundwater-discharge estimates in Spring and Snake Valleys on transmissivity estimates were bounded with alternative models. Annual distributed groundwater discharges from Spring and Snake Valleys in the alternative models totaled 151,000 and 227,000 acre-feet, respectively and represented 20 percent differences from the 187,000 acre-feet per year that discharges from the GBNP-C model. Transmissivity estimates in the basin fill between Baker and Big Springs changed less than 50 percent between the two alternative models. Potential effects of pumping from Snake Valley were estimated with the Great Basin National Park predictive (GBNP-P) model, which is a transient groundwater-flow model. The hydraulic conductivity of basin fill and transmissivity of basement rock were the GBNP-C model distributions. Specific yields were defined from aquifer tests. Captures of distributed groundwater and spring discharges were simulated in the GBNP-P model using a combination of well and drain packages in MODFLOW. Simulated groundwater captures could not exceed measured groundwater-discharge rates. Four groundwater-development scenarios were investigated where total annual withdrawals ranged from 10,000 to 50,000 acre-feet during a 200-year pumping period. Four additional scenarios also were simulated that added the effects of existing pumping in Snake Valley. Potential groundwater pumping locations were limited to nine proposed points of diversion. Results are presented as maps of groundwater capture and drawdown, time series of drawdowns and discharges from selected wells, and time series of discharge reductions from selected springs and control volumes. Simulated drawdown propagation was attenuated where groundwater discharge could be captured. General patterns of groundwater capture and water-table declines were similar for all scenarios. Simulated

  15. Comparative investigations of manual action representations: evidence that chimpanzees represent the costs of potential future actions involving tools

    PubMed Central

    Frey, Scott H.; Povinelli, Daniel J.

    2012-01-01

    The ability to adjust one's ongoing actions in the anticipation of forthcoming task demands is considered as strong evidence for the existence of internal action representations. Studies of action selection in tool use reveal that the behaviours that we choose in the present moment differ depending on what we intend to do next. Further, they point to a specialized role for mechanisms within the human cerebellum and dominant left cerebral hemisphere in representing the likely sensory costs of intended future actions. Recently, the question of whether similar mechanisms exist in other primates has received growing, but still limited, attention. Here, we present data that bear on this issue from a species that is a natural user of tools, our nearest living relative, the chimpanzee. In experiment 1, a subset of chimpanzees showed a non-significant tendency for their grip preferences to be affected by anticipation of the demands associated with bringing a tool's baited end to their mouths. In experiment 2, chimpanzees' initial grip preferences were consistently affected by anticipation of the forthcoming movements in a task that involves using a tool to extract a food reward. The partial discrepancy between the results of these two studies is attributed to the ability to accurately represent differences between the motor costs associated with executing the two response alternatives available within each task. These findings suggest that chimpanzees are capable of accurately representing the costs of intended future actions, and using those predictions to select movements in the present even in the context of externally directed tool use. PMID:22106426

  16. Action potential energetics at the organismal level reveal a trade-off in efficiency at high firing rates.

    PubMed

    Lewis, John E; Gilmour, Kathleen M; Moorhead, Mayron J; Perry, Steve F; Markham, Michael R

    2014-01-01

    The energetic costs of action potential (AP) production constrain the evolution of neural codes and brain networks. Cellular-level estimates of AP-related costs are typically based on voltage-dependent Na(+) currents that drive active transport by the Na(+)/K(+) ATPase to maintain the Na(+) and K(+) ion concentration gradients necessary for AP production. However, these estimates of AP cost have not been verified at the organismal level. Electric signaling in the weakly electric fish Eigenmannia virescens requires that specialized cells in an electric organ generate APs with large Na(+) currents at high rates (200-600 Hz). We measured these currents using a voltage-clamp protocol and then estimated the energetic cost at the cellular level using standard methods. We then used this energy-intensive signaling behavior to measure changes in whole-animal energetics for small changes in electric discharge rate. At low rates, the whole-animal measure of AP cost was similar to our cellular-level estimates. However, AP cost increased nonlinearly with increasing firing rates. We show, with a biophysical model, that this nonlinearity can arise from the increasing cost of maintaining AP amplitude at high rates. Our results confirm that estimates of energetic costs based on Na(+) influx are appropriate for low baseline firing rates, but that extrapolating to high firing rates may underestimate true costs in cases in which AP amplitude does not decrease. Moreover, the trade-off between energetic cost and firing rate suggests an additional constraint on the evolution of high-frequency signaling in neuronal systems. PMID:24381281

  17. DEPRESSION OF THE PHOTIC AFTER DISCHARGE OF FLASH EVOKED POTENTIALS BY PHYSOSTIGMINE, CARBARYL AND PROPOXUR AND THE RELATIONSHIP TO INHIBITION OF BRAIN CHOLINESTERASE

    EPA Science Inventory

    The effects of N-methyl carbamate pesticides on the photic after discharge (PhAD) of flash evoked potentials (FEPs) and the relationship between inhibition of brain cholinesterase (ChE) activity and the PhAD were evaluated. FEPs were recorded in Long Evans rats treated with physo...

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

    PubMed

    Yang, Li-Zhen; Zhu, Yi-Chun

    2015-07-01

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

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

    PubMed Central

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

    2014-01-01

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

  20. The effects of heart rate on the action potential of guinea-pig and human ventricular muscle.

    PubMed

    Attwell, D; Cohen, I; Eisner, D A

    1981-01-01

    1. On increasing the stimulation frequency of isolated pieces of guinea-pig ventricular muscle, the resting potential depolarizes, and the action potential duration and amplitude are reduced. On termination of the high frequency train of action potentials, these changes are reversed. 2. The resting potential changes are roughly exponential, with a time constant of the order of 10 sec, and are attributable to K+ accumulation in the extracellular space. They are not explicable in terms of known gating variables. 3. The action potential duration and amplitude recover much more slowly than the resting potential, after a high frequency train (half-time approximately 5 min). The time course of these recoveries is not exponential, and is slower after trains which produce more shortening of the action potential. The slow time course suggests that K+ accumulation is not the main cause of the changes in action potential shape. Furthermore, when a certain depolarization of the resting potential is produced by a high frequency train, there is a greater reduction of the action potential duration than that which occurs when the bathing [K+] is raised to produce the same depolarization (Reiter & Stickel, 1968). This is so even when a gradient of extracellular [K+] is induced in the preparation, to mimic non-uniform K+ accumulation. 4. Similarly, the shortening of the action potential produced by toxic doses or cardiotonic steroids is probably not the result of K+ accumulation. 5. The slow changes of the action potential shape produced by a high frequency train are not attributable to the effects of gating variables, nor (solely) to a rise in the intracellular Na concentration stimulating the electrogenic Na/K pump. The dye 3,3'-diethylthiadicarbocyanine, which blocks the Ca2+-activated K conductance in the erythrocyte, has no significant effect on the shape changes. 6. After a sudden change in heart rate, the QT interval of the human electrocardiogram (e.c.g.) changes slowly to a

  1. 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.

  2. Action potential-induced dendritic calcium dynamics correlated with synaptic plasticity in developing hippocampal pyramidal cells.

    PubMed

    Isomura, Y; Kato, N

    1999-10-01

    In hippocampal CA1 pyramidal cells, intracellular calcium increases are required for induction of long-term potentiation (LTP), an activity-dependent synaptic plasticity. LTP is known to develop in magnitude during the second and third postnatal weeks in the rats. Little is known, however, about development of intracellular calcium dynamics during the same postnatal weeks. We investigated postnatal development of intracellular calcium dynamics in the proximal apical dendrites of CA1 pyramidal cells by whole cell patch-clamp recordings and calcium imaging with the Ca(2+) indicator fura-2. Dendritic calcium increases induced by intrasomatically evoked action potentials were slight during the first postnatal week but gradually became robust 3 to 6-fold during the second and third postnatal weeks. These calcium increases were blocked by application of 250 microM CdCl(2), a nonspecific blocker for high-threshold voltage-dependent calcium channels (VDCCs). Under the voltage-clamp condition, both calcium currents and dendritic calcium accumulations induced by depolarization were larger at the late developmental stage (P15-18) than the early stage (P4-7), indicating developmental enhancement of calcium influx mediated by high-threshold VDCCs. Moreover, theta-burst stimulation (TBS), a protocol for LTP induction, induced large intracellular calcium increases at the late developmental stage, in synchrony with maturation of TBS-induced LTP. These results suggest that developmental enhancement of intracellular calcium increases induced by action potentials may underlie maturation of calcium-dependent functions such as synaptic plasticity in hippocampal neurons.

  3. Transport of chemical and microbial compounds from known wastewater discharges: Potential for use as indicators of human fecal contamination

    USGS Publications Warehouse

    Glassmeyer, S.T.; Furlong, E.T.; Kolpin, D.W.; Cahill, J.D.; Zaugg, S.D.; Werner, S.L.; Meyer, M.T.; Kryak, D.D.

    2005-01-01

    The quality of drinking and recreational water is currently (2005) determined using indicator bacteria. However, the culture tests used to analyze for these bacteria require a long time to complete and do not discriminate between human and animal fecal material sources. One complementary approach is to use chemicals found in human wastewater, which would have the advantages of (1) potentially shorter analysis times than the bacterial culture tests and (2) being selected for human-source specificity. At 10 locations, water samples were collected upstream and at two successive points downstream from a wastewaster treatment plant (WWTP); a treated effluent sample was also collected at each WWTP. This sampling plan was used to determine the persistence of a chemically diverse suite of emerging contaminants in streams. Samples were also collected at two reference locations assumed to have minimal human impacts. Of the 110 chemical analytes investigated in this project, 78 were detected at least once. The number of compounds in a given sample ranged from 3 at a reference location to 50 in a WWTP effluent sample. The total analyte load at each location varied from 0.018 μg/L at the reference location to 97.7 μg/L in a separate WWTP effluent sample. Although most of the compound concentrations were in the range of 0.01−1.0 μg/L, in some samples, individual concentrations were in the range of 5−38 μg/L. The concentrations of the majority of the chemicals present in the samples generally followed the expected trend:  they were either nonexistent or at trace levels in the upstream samples, had their maximum concentrations in the WWTP effluent samples, and then declined in the two downstream samples. This research suggests that selected chemicals are useful as tracers of human wastewater discharge.

  4. Determination of potential groundwater discharge zones into a Salt Lake using remote sensing techniques and in-situ measurements

    NASA Astrophysics Data System (ADS)

    Kilic, Ecenur; Kamil Yilmaz, Koray; Lutfi Suzen, M.

    2015-04-01

    Groundwater and surface water are integral components of the hydrologic system with strong feedback mechanisms and hence should be treated as a single resource. Existence of groundwater discharge into lakes is a very significant factor that affects both the water quantity of the lake as well as its ecological and biological diversity. The degree of interaction is more significant for shallow lakes because of their increased vulnerability due to limited volume and rapid changes in the extent and duration of the wet/dry cycles. The Salt Lake, located in Central Anatolia, Turkey, is a hyper-saline, shallow lake that is ranked as the second largest lake in Turkey. The majority of the lake dries during the late summer season enabling investigation of the lake bottom morphology. Through analysis of the high-resolution satellite images we identified circular features that may indicate possible groundwater seepage locations. The density and shape properties of these features were then investigated via spatial statistics to identify possible trends that can be linked to controlling mechanism(s) such as underlying sediments, geology, hydrogeology and wind patterns. The analysis was supported by field measurement of salt thickness at various locations in a systematic way. Long-term precipitation, lake level and groundwater level data were compared to investigate possible relationships and trends. In this presentation the framework to investigate remotely-sensed and in-situ measurements will be discussed with potential links to the groundwater recharge to the Salt Lake. Future work will focus on installing long-term monitoring networks in the lake.

  5. A 10-form gauge potential and an M-9-brane Wess-Zumino action in massive 11D theory

    NASA Astrophysics Data System (ADS)

    Sato, T.

    2000-03-01

    We discuss some properties of an M-9-brane in ``massive 11D theory'' proposed by Bergshoeff, Lozano and Ortin. A 10-form gauge potential is consistently introduced into the massive 11D supergravity, and an M-9-brane Wess-Zumino action is constructed as that of a gauged /σ-model. Using duality relations is crucial in deriving the action, which we learn from the study of a 9-form potential in 10D massive IIA theory. A target space solution of an M-9-brane with a non-vanishing 10-form gauge field is also obtained, whose source is shown to be the M-9-brane effective action.

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

    PubMed Central

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

    2012-01-01

    The ability to make electrical measurements inside cells has led to many important advances in electrophysiology1-6. 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 resolution1,2. 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 interior1,2, which limits how small the micropipette can be. Techniques that involve inserting metal or carbon microelectrodes into cells are subject to similar constraints4,7-9. Field-effect transistors (FETs) can also record electric potentials inside cells10, and since their performance does not depend on impedance11,12, 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 structures10, but the kink configuration and device design places limits on the probe size and the potential for multiplexing. Here we report a new approach where a SiO2 nanotube is synthetically integrated on top of a nanoscale FET. After penetrating the cell membrane, the SiO2 nanotube brings the cell cytosol into contact with the FET and enables the recording of 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 which is well below that accessible with other methods1,2,4. Studies of cardiomyocyte cells demonstrate that when brought close, the nanotubes of phospholipid-modified BIT-FETs spontaneously penetrate the cell membrane to yield stable, full-amplitude intracellular action

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

    PubMed

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

    2012-03-01

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

  8. 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

  9. Eudragit E100® potentiates the bactericidal action of ofloxacin against fluoroquinolone-resistant Pseudomonas aeruginosa.

    PubMed

    Romero, Verónica L; Pons, Patricia; Bocco, José L; Manzo, Rubén H; Alovero, Fabiana L

    2012-09-01

    We report the enhanced bactericidal activity of ofloxacin in drug-containing Eudragit E100(®) dispersions (EuCl-OFX) against Pseudomonas aeruginosa and the effect of the cationic polymer on bacterial membrane. Organisms treated with EuCl-OFX showed changes in cell morphology, altered outer membrane (OM) and cytoplasm with low electrodensity areas. Zeta potential of bacterial surface was shifted to positive. Sensitization to lytic agents was also observed. A profound effect on bacterial size, granularity and membrane depolarization was found by flow cytometry. Cultures exposed to drug-free polymer also showed some damaged bacterial membranes, but there was no significant cell death. Inhibition of P. aeruginosa by EuCl-OFX may involve surface effect and, to some extent, permeation effect. The cationic polymer act to mitigate the electronegativity of cell surface in the process of disorganizing the OM, rendering it more permeable to antibiotic. In addition, cytoplasmic membrane depolarization turns bacterial cell more vulnerable. The effects on membranes combined with the mechanism of action of quinolone explain the improved bactericidal action exhibited by EuCl-OFX. The behavior described for Eudragit E100(®) against P. aeruginosa may be a useful tool to broaden the spectrum of antibiotics whose clinical use is limited by the impermeability of the bacterial OM.

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

    PubMed Central

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

    2015-01-01

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

  11. Contribution of Na(v)1.8 sodium channels to action potential electrogenesis in DRG neurons.

    PubMed

    Renganathan, M; Cummins, T R; Waxman, S G

    2001-08-01

    C-type dorsal root ganglion (DRG) neurons can generate tetrodotoxin-resistant (TTX-R) sodium-dependent action potentials. However, multiple sodium channels are expressed in these neurons, and the molecular identity of the TTX-R sodium channels that contribute to action potential production in these neurons has not been established. In this study, we used current-clamp recordings to compare action potential electrogenesis in Na(v)1.8 (+/+) and (-/-) small DRG neurons maintained for 2-8 h in vitro to examine the role of sodium channel Na(v)1.8 (alpha-SNS) in action potential electrogenesis. Although there was no significant difference in resting membrane potential, input resistance, current threshold, or voltage threshold in Na(v)1.8 (+/+) and (-/-) DRG neurons, there were significant differences in action potential electrogenesis. Most Na(v)1.8 (+/+) neurons generate all-or-none action potentials, whereas most of Na(v)1.8 (-/-) neurons produce smaller graded responses. The peak of the response was significantly reduced in Na(v)1.8 (-/-) neurons [31.5 +/- 2.2 (SE) mV] compared with Na(v)1.8 (+/+) neurons (55.0 +/- 4.3 mV). The maximum rise slope was 84.7 +/- 11.2 mV/ms in Na(v)1.8 (+/+) neurons, significantly faster than in Na(v)1.8 (-/-) neurons where it was 47.2 +/- 1.3 mV/ms. Calculations based on the action potential overshoot in Na(v)1.8 (+/+) and (-/-) neurons, following blockade of Ca(2+) currents, indicate that Na(v)1.8 contributes a substantial fraction (80-90%) of the inward membrane current that flows during the rising phase of the action potential. We found that fast TTX-sensitive Na(+) channels can produce all-or-none action potentials in some Na(v)1.8 (-/-) neurons but, presumably as a result of steady-state inactivation of these channels, electrogenesis in Na(v)1.8 (-/-) neurons is more sensitive to membrane depolarization than in Na(v)1.8 (+/+) neurons, and, in the absence of Na(v)1.8, is attenuated with even modest depolarization. These observations

  12. 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.

  13. 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.

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  16. [Adrenaline potentiates antiepileptic but not sedative action of diazepam in rats].

    PubMed

    Serdiuk, S E; Gmiro, V E

    2012-02-01

    Intramuscular (i.m.) administration ofdiazepam in a dose of 10 mg/kg and adrenaline in a dose of 0.2 mg/kg prevents generalized clonic-tonic pentylenetetrazol (PTZ) seizures in 75-80 % of rats, but only in 35-40 % of rats it prevents local clonic PTZ seizures. In the above mentioned dose, diazepam causes a strong sedation, but adrenaline does not cause a sedative effects. The combined administration of diazepam and adrenaline in threshold independently ineffective doses prevents both clonic-tonic and clonic PTZ seizures in 80 % of rats without a sedation development. The basis for mechanism of potentiation of anticonvulsant action of diazepam is the stimulation of gastric mucosa afferents by adrenaline. PMID:22650067

  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. Effect of intense sound exposure on cochlear microphonics and whole nerve action potential

    NASA Astrophysics Data System (ADS)

    Yamamura, K.; Yamamoto, N.; Kohyama, A.; Sawada, Y.; Ohno, H.; Saitoh, Y.

    1989-06-01

    An investigation was carried out to determine whether or not the critical band with Temporary Threshold Shift (TTS) is affected by exposure to high frequency sound. The function of the cochlea and the 8th nerve in guinea pigs was estimated by the intensity function and maximum output voltage of cochlear microphonics (CM) and by whole nerve action potential (Ap). Our results showed that both the intensity function and the maximum output voltage of CM and Ap decreased. Ap obtained at the test frequency higher, by half an octave, than the center frequency of the exposure noise was especially lowered. These results suggest that the critical band with TTS of both Ap and CM may be affected in exposure to high frequency sound.

  19. Action potentials occur spontaneously in squid giant axons with moderately alkaline intracellular pH.

    PubMed

    Clay, J R; Shrier, A

    2001-10-01

    This report demonstrates a novel finding from the classic giant axon preparation of the squid. Namely, the axon can be made to fire autonomously (spontaneously occurring action potentials) when the intracellular pH (pH(i)) was increased to about 7.7, or higher. (Physiological pH(i) is 7.3.) The frequency of firing was 33 Hz (T = 5 degrees ). No changes in frequency or in the voltage waveform itself were observed when pH(i) was increased from 7.7 up to 8.5. In other words, the effect has a threshold at a pH(i) of about 7.7. A mathematical model that is sufficient to mimic these results is provided using a modified version of the Clay (1998) description of the axonal ionic currents.

  20. 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

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

    PubMed

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

    2016-01-01

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

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

    NASA Astrophysics Data System (ADS)

    He, Zhi Zhu; Liu, Jing

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

  3. A supervised multi-sensor matched filter for the detection of extracellular action potentials.

    PubMed

    Szymanska, Agnieszka F; Doty, Michael; Scannell, Kathryn V; Nenadic, Zoran

    2014-01-01

    Multi-sensor extracellular recording takes advantage of several electrode channels to record from multiple neurons at the same time. However, the resulting low signal-to-noise ratio (SNR) combined with biological noise makes signal detection, the first step of any neurophysiological data analysis, difficult. A matched filter was therefore designed to better detect extracellular action potentials (EAPs) from multi-sensor extracellular recordings. The detector was tested on tetrode data from a locust antennal lobe and assessed against three trained analysts. 25 EAPs and noise samples were selected manually from the data and used for training. To reduce complexity, the filter assumed that the underlying noise in the data was spatially white. The detector performed with an average TP and FP rate of 84.62% and 16.63% respectively. This high level of performance indicates the algorithm is suitable for widespread use.

  4. 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.

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

    PubMed Central

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

    2009-01-01

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

  6. Enhanced Action Potential Passage Through the Node of Ranvier of Myelinated Axons via Proton Hopping.

    PubMed

    Kier, Lemont; Hall, Lowell; Tombes, Robert M

    2015-01-01

    Nerve impulses travel along myelinated axons as much as 300-fold faster than they do along unmyelinated axons. Myelination is essential for normal nervous system behavior in vertebrates as illustrated by leukodystrophies, such as amyotrophic lateral sclerosis (ALS) or multiple sclerosis (MS), where myelin is degenerated or damaged. The increased conduction velocity that occurs in myelinated axons is dependent on gaps in the myelin called Nodes of Ranvier that are enriched in ion channels. These Nodes are separated by long stretches of myelin insulation where no transmembrane ion conductance occurs. It is believed that the action potential jumps or skips between nodes, conserving its information content, while maintaining its speed. In this study, a model is presented that implicates Nodes of Ranvier as responsible for regenerating the proton hopping that is responsible for nerve impulse conductance in myelinated axons.

  7. 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

  8. 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.

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

    PubMed

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

    2016-07-20

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

  10. 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

  11. Lung surgery - discharge

    MedlinePlus

    Thoracotomy - discharge; Lung tissue removal - discharge; Pneumonectomy - discharge; Lobectomy - discharge; Lung biopsy - discharge; Thoracoscopy - discharge; Video-assisted thoracoscopic surgery - discharge; VATS - ...

  12. 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

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

    PubMed Central

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

    2015-01-01

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

  14. Correlation of repolarization of ventricular monophasic action potential with ECG in the murine heart.

    PubMed

    Danik, Stephan; Cabo, Candido; Chiello, Christine; Kang, Sacha; Wit, Andrew L; Coromilas, James

    2002-07-01

    Transgenic mice have become important experimental models in the investigation of mechanisms causing cardiac arrhythmias because of the ability to create strains with alterations in repolarizing membrane currents. It is important to relate alterations in membrane currents in cells to their phenotypic expression on the electrocardiogram (ECG). The murine ECG, however, has unusual characteristics that make interpretation of the phenotypic expression of changes in ventricular repolarization uncertain. The major deflection representing the QRS (referred to as "a") is often followed by a secondary slower deflection ("b") and sometimes a subtle third deflection ("c"). To determine whether the second or third deflections or both represent ventricular repolarization, we recorded the ventricular monophasic action potential (MAP) in open-chest mice and correlated repolarization with the ECG. There was no significant correlation by linear regression, between action potential duration to 50% or 90% repolarization (APD(50) or APD(90)), respectively, of the MAP and either the interval from onset of Q to onset of b (Qb interval) or onset of c (Qc interval). Administration of 4-aminopyridine (4-AP) significantly prolonged APD(50) and APD(90) and the Qb interval, indicating that this deflection on the ECG represents part of ventricular repolarization. After 4-AP, the c wave disappeared, also suggesting that it represents a component of ventricular repolarization. Although it appears that both the b and c waves that follow the Q wave on the ECG represent ventricular repolarization, neither correlates exactly with APD(90) of the MAP. Therefore, an accurate measurement of complete repolarization of the murine ventricle cannot be obtained from the surface ECG. PMID:12063311

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

    PubMed Central

    2012-01-01

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

  16. Evaluation of the potential of soil remediation by direct multi-channel pulsed corona discharge in soil.

    PubMed

    Wang, Tie Cheng; Qu, Guangzhou; Li, Jie; Liang, Dongli

    2014-01-15

    A novel approach, named multi-channel pulsed corona discharge in soil, was developed for remediating organic pollutants contaminated soil, with p-nitrophenol (PNP) as the model pollutant. The feasibility of PNP degradation in soil was explored by evaluating effects of pulse discharge voltage, air flow rate and soil moisture on PNP degradation. Based on roles of chemically active species and evolution of degradation intermediates, PNP degradation processes were discussed. Experimental results showed that about 89.4% of PNP was smoothly degraded within 60min of discharge treatment at pulse discharge voltage 27kV, soil moisture 5% and air flow rate 0.8Lmin(-1), and the degradation process fitted the first-order kinetic model. Increasing pulse discharge voltage was found to be favorable for PNP degradation, but not for energy yield. There existed appropriate air flow rate and soil moisture for obtaining gratifying PNP degradation efficacy. Roles of radical scavenger and measurement of active species suggested that ozone, H2O2, and OH radicals played very important roles in PNP degradation. CN bond in PNP molecule was cleaved, and the main intermediate products such as hydroquinone, benzoquinone, catechol, phenol, acetic acid, formic acid, oxalic acid, NO2(-) and NO3(-) were identified. Possible pathway of PNP degradation in soil in such a system was proposed.

  17. [Evaluation of potentiality of combined SHF- and glow discharge in intensification of carbon dioxide and hydrogen processing within life support system].

    PubMed

    Klimarev, S I

    2011-01-01

    The article reports an experimental carbon dioxide hydration process in combined SHF- and glow discharge, and describes a design of SHF plasmatrones for CO2 processing at air pressure and in an integrated unit. Maximal transformation of 80% CO2 per a run was reached with the total input power of no more than 0.9 kW. Thermal zero lag of plasma forming, essentially instant and timely engagement and disengagement of thermal action on CO2-H2 mixture renders SHF-energy applicable to intensification of next generation life support technologies, processing of these gases within atmosphere regeneration system specifically.

  18. Kidney stones - lithotripsy - discharge

    MedlinePlus

    Extracorporeal shock wave lithotripsy - discharge; Shock wave lithotripsy - discharge; Laser lithotripsy - discharge; Percutaneous lithotripsy - discharge; Endoscopic lithotripsy - discharge; ESWL - ...

  19. Radical prostatectomy - discharge

    MedlinePlus

    ... prostatectomy - discharge; Laparoscopic radical prostatectomy - discharge; LRP - discharge; Robotic-assisted laparoscopic prostatectomy - discharge ; RALP - discharge; Pelvic lymphadenectomy - ...

  20. Post-Closure Monitoring Report for Corrective Action Unit 339: Area 12 Fleet Operations Steam Cleaning Discharge Area Nevada Test Site, Nevada

    SciTech Connect

    A. T. Urbon

    2001-08-01

    The Area 12 Fleet Operations Steam Cleaning site is located in the southeast portion of the Area 12 Camp at the Nevada Test Site (Figure 1). This site is identified in the Federal Facility Agreement and Consent Order (FFACO, 1996) as Corrective Action Site (CAS) 12-19-01 and is the only CAS assigned to Corrective Action Unit (CAU) 339. Post-closure sampling and inspection of the site were completed on March 23, 2001. Because of questionable representativeness and precision of the results, the site was resampled on June 12, 2001. Post-closure monitoring activities were scheduled biennially (every two years) in the Post-Closure Monitoring Plan provided in the December 1997 Closure Report for CAU 339: Area 12 Fleet Operations Steam Cleaning Discharge Area, Nevada Test Site (U.S. Department of Energy, Nevada Operations Office [DOE/NV], 1997). If after six years the rate of degradation appears to be so slow that the greatest concentration of total petroleum hydrocarbons (TPH) present at the site would not decay within 30 years of the site closure, the site will be reevaluated with consideration to enriching the impacted soil at the site to enhance the degradation process. A baseline for the site was established by sampling in 1997. Based on the recommendations from the 1999 post-closure monitoring report, samples were collected in 2000, earlier than originally proposed, because the 1999 sample results did not provide the expected decrease in TPH concentrations at the site. Sampling results from 2000 revealed favorable conditions for natural degradation at the CAU 339 site, but because of differing sample methods and heterogeneity of the soil, the data results from 2000 were not directly correlated with previous results. Post-closure monitoring activities for 2001 consisted of the following: Soil sample collection from three undisturbed plots (Plots A, B, and C, Figure 2); Sample analysis for TPH as oil and bio-characterization parameters (Comparative Enumeration Assay

  1. Size matters for violent discharge height and settling speed of Sphagnum spores: important attributes for dispersal potential

    PubMed Central

    Sundberg, Sebastian

    2010-01-01

    Background and Aims Initial release height and settling speed of diaspores are biologically controlled components which are key to modelling wind dispersal. Most Sphagnum (peat moss) species have explosive spore liberation. In this study, how capsule and spore sizes affect the height to which spores are propelled were measured, and how spore size and spore number of discharged particles relate to settling speed in the aspherical Sphagnum spores. Methods Spore discharge and spore cloud development were filmed in a closed chamber (nine species). Measurements were taken from snapshots at three stages of cloud development. Settling speed of spores (14 species) and clusters were timed in a glass tube. Key Results The maximum discharge speed measured was 3·6 m s−1. Spores reached a maximum height of 20 cm (average: 15 cm) above the capsule. The cloud dimensions at all stages were related positively to capsule size (R2 = 0·58–0·65). Thus species with large shoots (because they have large capsules) have a dispersal advantage. Half of the spores were released as singles and the rest as clusters (usually two to four spores). Single spores settled at 0·84–1·86 cm s−1, about 52 % slower than expected for spherical spores with the same diameters. Settling speed displayed a positive curvilinear relationship with spore size, close to predictions by Stokes' law for spherical spores with 68 % of the actual diameters. Light-coloured spores settled slower than dark spores. Settling speed of spore clusters agrees with earlier studies. Effective spore discharge and small, slowly settling spores appear particularly important for species in forested habitats. Conclusions The spore discharge heights in Sphagnum are among the greatest for small, wind-dispersed propagules. The discharge heights and the slow settling of spores affect dispersal distances positively and may help to explain the wide distribution of most boreal Sphagnum species. PMID:20123930

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

    PubMed Central

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

    2012-01-01

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

  3. A calcium-activated sodium conductance produces a long-duration action potential in the egg of a nemertean worm.

    PubMed Central

    Jaffe, L A; Kado, R T; Kline, D

    1986-01-01

    1. The egg of the nemertean worm Cerebratulus lacteus produced an action potential having a duration of about 9 min. We investigated the ionic conductances which accounted for this long-duration action potential. 2. The peak of the action potential was about +50 mV and depended on extracellular Ca2+, while the plateau potential was about +25 mV and depended on extracellular Na+. 3. Under voltage-clamp conditions, depolarization produced two temporally separate inward currents: a fast current which reached a peak at about 10 ms, and a slow current which took up to 1 min to reach its peak and lasted for several min. 4. The fast current was independent of extracellular Na+, but was blocked by removal of extracellular Ca2+. 5. The slow current was not seen when extracellular Na+ was replaced by choline+ or K+. 6. The slow current did not develop in Ca2+-free sea water, and was reduced to about half if Ca2+ was removed after the current had been initiated. 7. Microinjection of EGTA blocked the slow current, and reduced the action potential duration to about 1 min. 8. We concluded that a voltage-activated Ca2+ conductance produced the peak of the action potential, while a Ca2+-activated Na+ conductance produced its plateau. PMID:2442351

  4. Cardiac action potential duration and contractility in the intact dog heart.

    PubMed

    Drake-Holland, A J; Noble, M I; Pieterse, M; Schouten, V J; Seed, W A; ter Keurs, H E; Wohlfart, B

    1983-12-01

    The maximum rate of rise of left ventricular pressure (DP) and action potential duration (a.p.d.) were measured in closed-chest anaesthetized dogs with atrioventricular dissociation and beta-adrenergic blockade. Right ventricular stimulation was carried out with protocols consisting of a conditioning 'priming' period and a test period. When a single test stimulus was introduced at varying intervals after the priming period, DP was found to be maximal at 800-1000 ms. With this single test stimulus fixed at the optimum, DP was found to be a variable inverse function of the a.p.d. of the same beat; no positive correlation could be found between DP and a.p.d. When a second test stimulus at the optimum interval was introduced after the first, the DP (DP2) was found to be strongly dependent on that elicited by the first test stimulus (DP1); the relationship was positive, linear, independent of the method used to vary DP, and independent of whether DP1 was depressed or potentiated. The slope of the relationship was less than 1.0 and the line passed through the point where DP2 = DP1; this is the point of continuous stimulation at the optimum interval in a steady state. This result is consistent with the hypothesis that the coefficient relating DP1 to DP2, at constant a.p.d. of the first test pulse (AP1), is an index of the proportion of the activator of contraction stored during relaxation of test beat 1 which is released again on beat 2. In order to test the hypothesis that the remaining contractility depended on the action potential of test beat 1, AP1 was varied by changing the intervals between the priming stimuli. In order to determine the relationship between DP2 and AP1 it was necessary to carry out multiple regression analysis because DP2 was already known to be strongly dependent on DP1 (point 3 above), i.e. DP2 = BDP(DP1) + BAP(AP1 - D). This analysis yielded highly significant positive values for the coefficients BDP and BAP. This result is compatible with the

  5. 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

  6. Optimisation of Ionic Models to Fit Tissue Action Potentials: Application to 3D Atrial Modelling

    PubMed Central

    Lovell, Nigel H.; Dokos, Socrates

    2013-01-01

    A 3D model of atrial electrical activity has been developed with spatially heterogeneous electrophysiological properties. The atrial geometry, reconstructed from the male Visible Human dataset, included gross anatomical features such as the central and peripheral sinoatrial node (SAN), intra-atrial connections, pulmonary veins, inferior and superior vena cava, and the coronary sinus. Membrane potentials of myocytes from spontaneously active or electrically paced in vitro rabbit cardiac tissue preparations were recorded using intracellular glass microelectrodes. Action potentials of central and peripheral SAN, right and left atrial, and pulmonary vein myocytes were each fitted using a generic ionic model having three phenomenological ionic current components: one time-dependent inward, one time-dependent outward, and one leakage current. To bridge the gap between the single-cell ionic models and the gross electrical behaviour of the 3D whole-atrial model, a simplified 2D tissue disc with heterogeneous regions was optimised to arrive at parameters for each cell type under electrotonic load. Parameters were then incorporated into the 3D atrial model, which as a result exhibited a spontaneously active SAN able to rhythmically excite the atria. The tissue-based optimisation of ionic models and the modelling process outlined are generic and applicable to image-based computer reconstruction and simulation of excitable tissue. PMID:23935704

  7. Compound Muscle Action Potential and Motor Function in Children with Spinal Muscular Atrophy

    PubMed Central

    Lewelt, Aga J.; Krosschell, Kristin J.; Scott, Charles; Sakonju, Ai; Kissel, John T.; Crawford, Thomas O.; Acsadi, Gyula; D'Anjou, Guy; Elsheikh, Bakri; Reyna, Sandra P.; Schroth, Mary K.; Maczulski, Jo Anne; Stoddard, Gregory J.; Elovic, Elie; Swoboda, Kathryn J.

    2010-01-01

    Introduction Reliable outcome measures that reflect the underlying disease process and correlate with motor function in children with SMA are needed for clinical trials. Methods Maximum ulnar compound muscle action potential (CMAP) data were collected at 2 visits over a 4–6 week period in children with SMA types II and III, ages 2–17 years old, at 4 academic centers. Primary functional outcome measures included the Modified Hammersmith Functional Motor Scale (MHFMS) and MHFMS-Extend. Results CMAP negative peak amplitude and area showed excellent discrimination between the ambulatory and non-ambulatory SMA cohorts (ROC=0.88). CMAP had excellent test-retest reliability (ICC=0.96–0.97, n=64) and moderate to strong correlation with the MHFMS and MHFMS-Extend (r=0.61–0.73, n=68, p<0.001). Discussion Maximum ulnar CMAP amplitude and area is a feasible, valid and reliable outcome measure for use in pediatric multicenter clinical trials in SMA. CMAP correlates well with motor function and has potential value as a relevant surrogate for disease status. PMID:20737553

  8. 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

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

    PubMed Central

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

    2016-01-01

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

  10. Evaluating the noise in electrically evoked compound action potential measurements in cochlear implants.

    PubMed

    Undurraga, Jaime A; Carlyon, Robert P; Wouters, Jan; van Wieringen, Astrid

    2012-07-01

    Electrically evoked compound action potentials (ECAPs) are widely used to study the excitability of the auditory nerve and stimulation properties in cochlear implant (CI) users. However, ECAP detection can be difficult and very subjective at near-threshold stimulation levels or in spread of excitation measurements. In this study, we evaluated the statistical properties of the background noise (BN) and the postaverage residual noise (RN) in ECAP measurements in order to determine an objective detection criterion. For the estimation of the BN and the RN, a method currently used in auditory brainstem response measurements was applied. The potential benefit of using weighted (Bayesian) averages was also examined. All estimations were performed with a set of approximately 360 ECAP measurements recorded from five human CI users of the CII or HiRes90K device (advanced bionics). Results demonstrated that the BN was normally distributed and the RN decreased according to the square root of the number of averages. No additional benefit was observed by using weighted averaging. The noise was not significantly different either at different stimulation intensities or across recording electrodes along the cochlea. The analysis of the statistical properties of the noise indicated that a signal-to-noise ratio of 1.7 dB as a detection criterion corresponds to a false positive detection rate of 1% with the used measurement setup.

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

    PubMed

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

    2016-01-01

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

  12. 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.

  13. Optophysiological Approach to Resolve Neuronal Action Potentials with High Spatial and Temporal Resolution in Cultured Neurons

    PubMed Central

    Pagès, Stéphane; Côté, Daniel; De Koninck, Paul

    2011-01-01

    Cell to cell communication in the central nervous system is encoded into transient and local membrane potential changes (ΔVm). Deciphering the rules that govern synaptic transmission and plasticity entails to be able to perform Vm recordings throughout the entire neuronal arborization. Classical electrophysiology is, in most cases, not able to do so within small and fragile neuronal subcompartments. Thus, optical techniques based on the use of fluorescent voltage-sensitive dyes (VSDs) have been developed. However, reporting spontaneous or small ΔVm from neuronal ramifications has been challenging, in part due to the limited sensitivity and phototoxicity of VSD-based optical measurements. Here we demonstrate the use of water soluble VSD, ANNINE-6plus, with laser-scanning microscopy to optically record ΔVm in cultured neurons. We show that the sensitivity (>10% of fluorescence change for 100 mV depolarization) and time response (sub millisecond) of the dye allows the robust detection of action potentials (APs) even without averaging, allowing the measurement of spontaneous neuronal firing patterns. In addition, we show that back-propagating APs can be recorded, along distinct dendritic sites and within dendritic spines. Importantly, our approach does not induce any detectable phototoxic effect on cultured neurons. This optophysiological approach provides a simple, minimally invasive, and versatile optical method to measure electrical activity in cultured neurons with high temporal (ms) resolution and high spatial (μm) resolution. PMID:22016723

  14. The interactions between potassium and sodium currents in generating action potentials in the rat sympathetic neurone.

    PubMed Central

    Belluzzi, O; Sacchi, O

    1988-01-01

    V, indicating that at these membrane potentials the IA current mainly, if not exclusively, contributes to the action potential falling phase. 5. The basic features of the sympathetic neurone action potential were reconstructed by simulations based on present and previous voltage-clamp characterization of the IA, IK(V) and INa conductances.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:2457694

  15. Catastrophic meltwater discharge down the Hudson Valley: a potential trigger for the Intra-Allerød cold period

    USGS Publications Warehouse

    Donnelly, Jeffrey P.; Driscoll, Neal W.; Uchupi, Elazar; Keigwin, Loyd D.; Schwab, William C.; Thieler, E. Robert; Swift, Stephen A.

    2005-01-01

    Glacial freshwater discharge to the Atlantic Ocean during deglaciation may have inhibited oceanic thermohaline circulation, and is often postulated to have driven climatic fluctuations. Yet attributing meltwater-discharge events to particular climate oscillations is problematic, because the location, timing, and amount of meltwater discharge are often poorly constrained. We present evidence from the Hudson Valley and the northeastern U.S. continental margin that establishes the timing of the catastrophic draining of Glacial Lake Iroquois, which breached the moraine dam at the Narrows in New York City, eroded glacial lake sediments in the Hudson Valley, and deposited large sediment lobes on the New York and New Jersey continental shelf ca. 13,350 yr B.P. Excess 14C in Cariaco Basin sediments indicates a slowing in thermohaline circulation and heat transport to the North Atlantic at that time, and both marine and terrestrial paleoclimate proxy records around the North Atlantic show a short-lived (<400 yr) cold event (Intra-Aller??d cold period) that began ca. 13,350 yr B.P. The meltwater discharge out the Hudson Valley may have played an important role in triggering the Intra-Aller??d cold period by diminishing thermohaline circulation. ?? 2005 Geological Society of America.

  16. Differential action potentials and firing patterns in injured and uninjured small dorsal root ganglion neurons after nerve injury.

    PubMed

    Zhang, Xu-Feng; Zhu, Chang Z; Thimmapaya, Rama; Choi, Won S; Honore, Prisca; Scott, Victoria E; Kroeger, Paul E; Sullivan, James P; Faltynek, Connie R; Gopalakrishnan, Murali; Shieh, Char-Chang

    2004-05-29

    The profile of tetrodotoxin sensitive (TTX-S) and resistant (TTX-R) Na(+) channels and their contribution to action potentials and firing patterns were studied in isolated small dorsal root ganglion (DRG) neurons after L5/L6 spinal nerve ligation (SNL). Total TTX-R Na(+) currents and Na(v) 1.8 mRNA were reduced in injured L5 DRG neurons 14 days after SNL. In contrast, TTX-R Na(+)currents and Na(v) 1.8 mRNA were upregulated in uninjured L4 DRG neurons after SNL. Voltage-dependent inactivation of TTX-R Na(+) channels in these neurons was shifted to hyperpolarized potentials by 4 mV. Two types of neurons were identified in injured L5 DRG neurons after SNL. Type I neurons (57%) had significantly lower threshold but exhibited normal resting membrane potential (RMP) and action potential amplitude. Type II neurons (43%) had significantly smaller action potential amplitude but retained similar RMP and threshold to those from sham rats. None of the injured neurons could generate repetitive firing. In the presence of TTX, only 26% of injured neurons could generate action potentials that had smaller amplitude, higher threshold, and higher rheobase compared with sham rats. In contrast, action potentials and firing patterns in uninjured L4 DRG neurons after SNL, in the presence or absence of TTX, were not affected. These results suggest that TTX-R Na(+) channels play important roles in regulating action potentials and firing patterns in small DRG neurons and that downregulation in injured neurons and upregulation in uninjured neurons confer differential roles in shaping electrogenesis, and perhaps pain transmission, in these neurons. PMID:15120592

  17. Differentiation of the action potential in the smooth muscle of canine gastric antrum using calcium-inhibitory drugs.

    PubMed

    Hohnsbein, J; Golenhofen, K

    1985-03-01

    Electrical and mechanical activity were recorded simultaneously in smooth muscle preparations from the antrum region of canine stomach by means of a single sucrose gap technique (SGT). The SGT was optimized to permit stable recording from multicellular smooth muscle preparations over several hours of electrical and mechanical activity with little disturbance of their normal properties. Acetylcholine (ACh, 10(-8) to 10(-6) M) induced or augmented dose-dependently the electrical and mechanical activity. The plateau of the action potential complex was elevated by ACh, while the contraction was increased in linear correlation to the magnitude of the plateau component. In spontaneously active (or in ACh-stimulated) preparations TEA (5 to 20 mM) magnified the plateau component, induced or strengthened spikes on the plateau ('secondary spikes'), and induced or strengthened phasic contractions. Nifedipine (10(-6) M) abolished secondary spikes, part of the plateau component of the action potential, and suppressed mechanical activity. The complex action potential of canine gastric antrum can be differentiated into (a) a basic action potential, consisting of an initial, primary spike and a plateau depolarization; this basic action potential is resistant to nifedipine and does not trigger any mechanical activity; and (b) a nifedipine-sensitive component (calcium component), which consists of an augmentation of the plateau depolarization and of secondary spikes, and which is responsible for the initiation of mechanical activity.

  18. An experimental study on the physical properties of the cupula. Effect of cupular sectioning on the ampullary nerve action potential.

    PubMed

    Suzuki, M; Harada, Y; Kishimoto, A

    1985-01-01

    The frog posterior semicircular canal (PSC) was isolated and a part of the ampullary wall was cut to allow removal of the cupula from the crista. The cupula was replaced on the crista and the PSC ampullary action potential was recorded. The cupula was again removed and was sectioned in half, either in the plane vertical to the crista (vertical sectioning), or in the plane parallel to the crista (horizontal sectioning). The sectioned half of the cupula was then replaced on the crista. The action potentials after replacement of the vertical or horizontal segments of the cupula were compared to those achieved when the entire cupula was replaced. After vertical sectioning, the action potentials were significantly reduced; they were 50.3% of the completely replaced cupula when a small stimulus was used and 79.1% when a large stimulus was used. A reduced attachment surface between the cupular base and the crista is possibly responsible for the decreased action potential in the vertically sectioned specimen. After horizontal sectioning, the action potentials were 64.5% for the small stimulus and 108.2% for the large stimulus. These results indicate that elicited responses are related to the height of the cupula and the deflection angle. This further suggests that the movement of the cupula is represented by that of the elastic system.

  19. A new method for the extraction and classification of single motor unit action potentials from surface EMG signals.

    PubMed

    Gazzoni, Marco; Farina, Dario; Merletti, Roberto

    2004-07-30

    It has been shown that multi-channel surface EMG allows assessment of anatomical and physiological single motor unit (MU) properties. To get this information, the action potentials of single MUs should be extracted from the interference EMG signals. This study describes an automatic system for the detection and classification of MU action potentials from multi-channel surface EMG signals. The methods for the identification and extraction of action potentials from the raw signals and for their clustering into the MUs to which they belong are described. The segmentation phase is based on the matched Continuous Wavelet Transform (CWT) while the classification is performed by a multi-channel neural network that is a modified version of the multi-channel Adaptive Resonance Theory networks. The neural network can adapt to slow changes in the shape of the MU action potentials. The method does not require any interaction of the operator. The technique proposed was validated on simulated signals, at different levels of force, generated by a structure based surface EMG model. The MUs identified from the simulated signals covered almost the entire recruitment curve. Thus, the proposed algorithm was able to identify a MU sample representative of the muscle. Results on experimental signals recorded from different muscles and conditions are reported, showing the possibility of investigating anatomical and physiological properties of the detected MUs in a variety of practical cases. The main limitation of the approach is that complete firing patterns can be obtained only in specific cases due to MU action potential superpositions.

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

    Abee, T; Krockel, L; Hill, C

    1995-12-01

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

  2. Mechano-perception in Chara cells: the influence of salinity and calcium on touch-activated receptor potentials, action potentials and ion transport.

    PubMed

    Shepherd, Virginia A; Beilby, Mary J; Al Khazaaly, Sabah A S; Shimmen, Teruo

    2008-11-01

    This paper investigates the impact of increased salinity on touch-induced receptor and action potentials of Chara internodal cells. We resolved underlying changes in ion transport by current/voltage analysis. In a saline medium with a low Ca(2+) ion concentration [(Ca(2+))(ext)], the cell background conductance significantly increased and proton pump currents declined to negligible levels, depolarizing the membrane potential difference (PD) to the excitation threshold [action potential (AP)(threshold)]. The onset of spontaneous repetitive action potentials further depolarized the PD, activating K(+) outward rectifying (KOR) channels. K(+) efflux was then sustained and irrevocable, and cells were desensitized to touch. However, when [Ca(2+)](ext) was high, the background conductance increased to a lesser extent and proton pump currents were stimulated, establishing a PD narrowly negative to AP(threshold). Cells did not spontaneously fire, but became hypersensitive to touch. Even slight touch stimulus induced an action potential and further repetitive firing. The duration of each excitation was extended when [Ca(2+)](ext) was low. Cell viability was prolonged in the absence of touch stimulus. Chara cells eventually depolarize and die in the saline media, but touch-stimulated and spontaneous excitation accelerates the process in a Ca(2+)-dependent manner. Our results have broad implications for understanding the interactions between mechano-perception and salinity stress in plants.

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

    PubMed

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

    2015-02-01

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

  4. 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

  5. Action potential propagation imaged with high temporal resolution near-infrared video microscopy and polarized light

    PubMed Central

    Schei, Jennifer L.; McCluskey, Matthew D.; Foust, Amanda J.; Yao, Xin-Cheng; Rector, David M.

    2008-01-01

    To identify the neural constituents responsible for generating polarized light changes, we created spatially resolved movies of propagating action potentials from stimulated lobster leg nerves using both reflection and transmission imaging modalities. Changes in light polarization are associated with membrane depolarization and provide sub-millisecond temporal resolution. Typically, signals are detected using light transmitted through tissue; however, because we eventually would like to apply polarization techniques in-vivo, reflected light is required. In transmission mode, the optical signal was largest throughout the center of the nerve, suggesting that most of the optical signal arose from the inner nerve bundle. In reflection mode, polarization changes were largest near the edges, suggesting that most of the optical signal arose from the outer sheath. In support of these observations, an optical model of the tissue showed that the outer sheath is more reflective while the inner nerve bundle is more transmissive. In order to apply these techniques in-vivo, we must consider that brain tissue does not have a regular orientation of processes as in the lobster nerve. We tested the effect of randomizing cell orientation by tying the nerve in an overhand knot prior to imaging, producing polarization changes that can be imaged even without regular cell orientations. PMID:18272402

  6. 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

  7. 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.

  8. Action Potential Energy Efficiency Varies Among Neuron Types in Vertebrates and Invertebrates

    PubMed Central

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

    2010-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

    Eftekharsadat, Bina; Habibzadeh, Afshin; Kolahi, Babak

    2015-01-01

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

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

    PubMed Central

    Quotb, Adam; Bornat, Yannick; Renaud, Sylvie

    2011-01-01

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

  12. 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.

  13. Action potential duration dispersion and alternans in simulated heterogeneous cardiac tissue with a structural barrier.

    PubMed

    Krogh-Madsen, Trine; Christini, David J

    2007-02-15

    Structural barriers to wave propagation in cardiac tissue are associated with a decreased threshold for repolarization alternans both experimentally and clinically. Using computer simulations, we investigated the effects of a structural barrier on the onset of spatially concordant and discordant alternans. We used two-dimensional tissue geometry with heterogeneity in selected potassium conductances to mimic known apex-base gradients. Although we found that the actual onset of alternans was similar with and without the structural barrier, the increase in alternans magnitude with faster pacing was steeper with the barrier--giving the appearance of an earlier alternans onset in its presence. This is consistent with both experimental structural barrier findings and the clinical observation of T-wave alternans occurring at slower pacing rates in patients with structural heart disease. In ionically homogeneous tissue, discordant alternans induced by the presence of the structural barrier arose at intermediate pacing rates due to a source-sink mismatch behind the barrier. In heterogeneous tissue, discordant alternans occurred during fast pacing due to a barrier-induced decoupling of tissue with different restitution properties. Our results demonstrate a causal relationship between the presence of a structural barrier and increased alternans magnitude and action potential duration dispersion, which may contribute to why patients with structural heart disease are at higher risk for ventricular tachyarrhythmias.

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

    PubMed

    Galati, Domenico F; 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

  15. Modeling back propagating action potential in weakly excitable dendrites of neocortical pyramidal cells.

    PubMed Central

    Rapp, M; Yarom, Y; Segev, I

    1996-01-01

    Simultaneous recordings from the soma and apical dendrite of layer V neocortical pyramidal cells of young rats show that, for any location of current input, an evoked action potential (AP) always starts at the axon and then propagates actively, but decrementally, backward into the dendrites. This back-propagating AP is supported by a low density (-gNa = approximately 4 mS/cm2) of rapidly inactivating voltage-dependent Na+ channels in the soma and the apical dendrite. Investigation of detailed, biophysically constrained, models of reconstructed pyramidal cells shows the following. (i) The initiation of the AP first in the axon cannot be explained solely by morphological considerations; the axon must be more excitable than the soma and dendrites. (ii) The minimal Na+ channel density in the axon that fully accounts for the experimental results is about 20-times that of the soma. If -gNa in the axon hillock and initial segment is the same as in the soma [as recently suggested by Colbert and Johnston [Colbert, C. M. & Johnston, D. (1995) Soc. Neurosci. Abstr. 21, 684.2

  16. Modeling back propagating action potential in weakly excitable dendrites of neocortical pyramidal cells.

    PubMed

    Rapp, M; Yarom, Y; Segev, I

    1996-10-15

    Simultaneous recordings from the soma and apical dendrite of layer V neocortical pyramidal cells of young rats show that, for any location of current input, an evoked action potential (AP) always starts at the axon and then propagates actively, but decrementally, backward into the dendrites. This back-propagating AP is supported by a low density (-gNa = approximately 4 mS/cm2) of rapidly inactivating voltage-dependent Na+ channels in the soma and the apical dendrite. Investigation of detailed, biophysically constrained, models of reconstructed pyramidal cells shows the following. (i) The initiation of the AP first in the axon cannot be explained solely by morphological considerations; the axon must be more excitable than the soma and dendrites. (ii) The minimal Na+ channel density in the axon that fully accounts for the experimental results is about 20-times that of the soma. If -gNa in the axon hillock and initial segment is the same as in the soma [as recently suggested by Colbert and Johnston [Colbert, C. M. & Johnston, D. (1995) Soc. Neurosci. Abstr. 21, 684.2

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

    PubMed

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

    2015-02-01

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

  18. An Improved Genetically Encoded Red Fluorescent Ca2+ Indicator for Detecting Optically Evoked Action Potentials

    PubMed Central

    Kobayashi, Chiaki; Ikegaya, Yuji; Nakai, Junichi

    2012-01-01

    Genetically encoded Ca2+ indicators (GECIs) are powerful tools to image activities of defined cell populations. Here, we developed an improved red fluorescent GECI, termed R-CaMP1.07, by mutagenizing R-GECO1. In HeLa cell assays, R-CaMP1.07 exhibited a 1.5–2-fold greater fluorescence response compared to R-GECO1. In hippocampal pyramidal neurons, R-CaMP1.07 detected Ca2+ transients triggered by single action potentials (APs) with a probability of 95% and a signal-to-noise ratio >7 at a frame rate of 50 Hz. The amplitudes of Ca2+ transients linearly correlated with the number of APs. The expression of R-CaMP1.07 did not significantly alter the electrophysiological properties or synaptic activity patterns. The co-expression of R-CaMP1.07 and channelrhodpsin-2 (ChR2), a photosensitive cation channel, in pyramidal neurons demonstrated that R-CaMP1.07 was applicable for the monitoring of Ca2+ transients in response to optically evoked APs, because the excitation light for R-CaMP1.07 hardly activated ChR2. These technical advancements provide a novel strategy for monitoring and manipulating neuronal activity with single cell resolution. PMID:22808076

  19. 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.

  20. 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.

  1. 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.

  2. Latencies in action potential stimulation in a two-dimensional bidomain: A numerical simulation

    NASA Astrophysics Data System (ADS)

    Barach, John Paul

    1991-05-01

    A numerical simulation is performed in which a uniform planar slab of idealized cardiac tissue is stimulated at the center. The cardiac slab is modeled as an anisotropic bidomain; within each domain current flow is determined by a forced diffusion equation in which the transmembrane current connecting the domains provides the forcing term. An action potential (AP) propagates outward after a time latency dependent upon the stimulus size and the physiological variables. Its isochrones are elliptical with an asymmetry that is a small fraction of the imposed asymmetry in resistivity. External voltages resemble the first derivative of those in the internal domain and tests with continuing stimuli exhibit a relaxation time of about 3 ms and space constants that agree with other work. The AP latency increases very strongly near threshold stimulus and decreases as the log (stimulus) for large stimuli in the ``virtual cathode'' range. Latencies in the longitudinal, transverse, and diagonal directions are found to be the same over a wide range of stimulus size and type.

  3. Improved health and growth of fish fed mannan oligosaccharides: potential mode of action.

    PubMed

    Torrecillas, Silvia; Montero, Daniel; Izquierdo, Marisol

    2014-02-01

    Nowadays, aquaculture industry still confronts several disease-related problems mainly caused by viruses, bacteria and parasites. In the last decade, the use of mannan oligosaccharides (MOS) in fish production has received increased attention due to its beneficial effects on fish performance and disease resistance. This review shows the MOS use in aquaculture with a specific emphasis on the effectiveness of the several MOS forms available in the market related to disease resistance, fish nutrition and the possible mechanisms involved. Among the main beneficial effects attributed to MOS dietary supplementation, enhanced fish performance, feed efficiency and pathogen protection by potentiation of the systemic and local immune system and the reinforcement of the epithelial barrier structure and functionality are some of the most commonly demonstrated benefits. These combined effects suggest that the reinforcement of the intestinal integrity and functionality, together with the stimulation of the innate immune system, are the primary mode of action of MOS in fish. However, the supplementation strategy related to the structure of the MOS added, the correct dose and duration, as well as fish species, size and culture conditions are determinant factors to achieve improvements in health status and growth performance.

  4. Molecular actions and therapeutic potential of lithium in preclinical and clinical studies of CNS disorders.

    PubMed

    Chiu, Chi-Tso; Chuang, De-Maw

    2010-11-01

    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.

  5. Ionic mechanisms maintaining action potential conduction velocity at high firing frequencies in an unmyelinated axon.

    PubMed

    Cross, Kevin P; Robertson, R Meldrum

    2016-05-01

    The descending contralateral movement detector (DCMD) is a high-performance interneuron in locusts with an axon capable of transmitting action potentials (AP) at more than 500 Hz. We investigated biophysical mechanisms for fidelity of high-frequency transmission in this axon. We measured conduction velocities (CVs) at room temperature during exposure to 10 mmol/L cadmium, a calcium current antagonist, and found significant reduction in CV with reduction at frequencies >200 Hz of ~10%. Higher temperatures induced greater CV reductions during exposure to cadmium across all frequencies of ~20-30%. Intracellular recordings during 15 min of exposure to cadmium or nickel, also a calcium current antagonist, revealed an increase in the magnitude of the afterhyperpolarization potential (AHP) and the time to recover to baseline after the AHP (Medians for Control: -19.8%; Nickel: 167.2%; Cadmium: 387.2%), that could be due to a T-type calcium current. However, the removal of extracellular calcium did not mimic divalent cation exposure suggesting calcium currents are not the cause of the AHP increase. Computational modeling showed that the effects of the divalent cations could be modeled with a persistent sodium current which could be blocked by high concentrations of divalent cations. Persistent sodium current shortened the AHP duration in our models and increased CV for high-frequency APs. We suggest that faithful, high-frequency axonal conduction in the DCMD is enabled by a mechanism that shortens the AHP duration like a persistent or resurgent sodium current. PMID:27225630

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

    PubMed

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

    2016-02-01

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

  7. 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

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

    PubMed

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

    2016-10-01

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

  9. 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

  10. 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.

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

    PubMed

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

    2016-02-01

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

  12. Action potential waveform voltage clamp shows significance of different Ca2+ channel types in developing ascidian muscle

    PubMed Central

    Dallman, Julia E; Dorman, Jennie B; Moody, William J

    2000-01-01

    Early in development, ascidian muscle cells generate spontaneous, long-duration action potentials that are mediated by a high-threshold, inactivating Ca2+ current. This spontaneous activity is required for appropriate physiological development.Mature muscle cells generate brief action potentials only in response to motor neuron input. The mature action potential is mediated by a high-threshold sustained Ca2+ current.Action potentials recorded from these two stages were imposed as voltage-clamp commands on cells of the same and different stages from which they were recorded. This strategy allowed us to study how immature and mature Ca2+ currents are optimized to their particular functions.Total Ca2+ entry during an action potential did not change during development. The developmental increase in Ca2+ current density exactly compensated for decreased spike duration. This compensation was a function purely of Ca2+ current density, not of the transition from immature to mature Ca2+ current types.In immature cells, Ca2+ entry was spread out over the entire waveform of spontaneous activity, including the interspike voltage trajectory. This almost continuous Ca2+ entry may be important in triggering Ca2+-dependent developmental programmes, and is a function of the slightly more negative voltage dependence of the immature Ca2+ current.In contrast, Ca2+ entry in mature cells was confined to the action potential itself, because of the slightly more positive voltage dependence of the mature Ca2+ current. This may be important in permitting rapid contraction-relaxation cycles during larval swimming.The inactivation of the immature Ca2+ current serves to limit the frequency and burst duration of spontaneous activity. The sustained kinetics of the mature Ca2+ current permit high-frequency firing during larval swimming. PMID:10766919

  13. Improved integration potential for calcium-phosphate-coated implants after glow-discharge and water-storage.

    PubMed

    Sendax, V I; Baier, R E

    1992-01-01

    Laboratory and clinical data support the conclusion that Radio-Frequency-Glow-Discharge-Treatment (RFGDT) of calcium-phosphate-coated implants can accelerate their functional integration with bone at host sites. In addition to the benefits of surface cleaning and activation associated with RFGDT, a period of water-storage prior to implantation also seems to be beneficial in eluting easily solubilized alkaline calcium components.

  14. A thermal profile method to identify potential ground-water discharge areas and preferred salmonid habitats for long river reaches

    USGS Publications Warehouse

    Vaccaro, J.J.; Maloy, K.J.

    2006-01-01

    The thermal regime of riverine systems is a major control on aquatic ecosystems. Ground water discharge is an important abiotic driver of the aquatic ecosystem because it provides preferred thermal structure and habitat for different types of fish at different times in their life history. In large diverse river basins with an extensive riverine system, documenting the thermal regime and ground-water discharge is difficult and problematic. A method was developed to thermally profile long (5-25 kilometers) river reaches by towing in a Lagrangian framework one or two probes that measure temperature, depth, and conductivity. One probe is towed near the streambed and, if used, a second probe is towed near the surface. The probes continuously record data at 1-3-second intervals while a Global Positioning System logs spatial coordinates. The thermal profile provides valuable information about spatial and temporal variations in habitat, and, notably, indicates ground-water discharge areas. This method was developed and tested in the Yakima River Basin, Washington, in summer 2001 during low flows in an extreme drought year. The temperature profile comprehensively documents the longitudinal distribution of a river's temperature regime that cannot be captured by fixed station data. The example profile presented exhibits intra-reach diversity that reflects the many factors controlling the temperature of a parcel of water as it moves downstream. Thermal profiles provide a new perspective on riverine system temperature regimes that represent part of the aquatic habitat template for lotic community patterns.

  15. A simple circuit for producing vertical arrays of analogue signals and dot raster displays of nerve and muscle action potentials.

    PubMed

    Miles, T S; Woodland, M J

    1986-03-01

    It is often helpful to display analogue signals such as electromyograms, electroencephalograms, nerve action potentials, etc., in a regular vertical array. A special case of this display is the widely-used dot raster. This paper describes a simple circuit which enables up to 31 analogue signals to be thus displayed on an analogue storage oscilloscope screen or X-Y plotter. A modification permits up to 255 trials to be displayed. The same circuit produces a standard, dot raster display from standard pulses representing nerve or muscle cell action potentials.

  16. 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.

  17. 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

  18. Spontaneous miniature hyperpolarizations affect threshold for action potential generation in mudpuppy cardiac neurons.

    PubMed

    Parsons, Rodney L; Barstow, Karen L; Scornik, Fabiana S

    2002-09-01

    Mudpuppy parasympathetic neurons exhibit spontaneous miniature hyperpolarizations (SMHs) that are generated by potassium currents, which are spontaneous miniature outward currents (SMOCs), flowing through clusters of large conductance voltage- and calcium (Ca(2+))-activated potassium (BK) channels. The underlying SMOCs are initiated by a Ca(2+)-induced Ca(2+) release (CICR) mechanism. Perforated-patch whole cell voltage recordings were used to determine whether activation of SMHs contributed to action potential (AP) repolarization or affected the latency to AP generation. Blockade of BK channels by iberiotoxin (IBX, 100 nM) slowed AP repolarization and increased AP duration. Treatment with omega-conotoxin GVIA (3 microM) or nifedipine (10 microM) to inhibit Ca(2+) influx through N- or L-type voltage-dependent calcium channels (VDCCs), respectively, also decreased the rate of AP repolarization and increased AP duration. Elimination of CICR by treatment with either thapsigargin (1 microM) or ryanodine (10 microM) produced no significant change in AP repolarization or duration. Blockade of BK channels with IBX and inhibition of N-type VDCCs with omega-conotoxin GVIA, but not inhibition of L-type VDCCs with nifedipine, decreased the latency of AP generation. A decrease in latency to AP generation occurred with elimination of SMHs by inhibition of CICR following treatment with thapsigargin. Ryanodine treatment decreased AP latency in three of six cells. Apamin (100 nM) had no affect on AP repolarization, duration, or latency to AP generation, but did decrease the hyperpolarizing afterpotential (HAP). Inhibition of L-type VDCCs by nifedipine also decreased HAP amplitude. Inhibition of CICR by either thapsigargin or ryanodine treatment increased the number of APs generated with long depolarizing current pulses, whereas exposure to IBX or omega-conotoxin GVIA depressed excitability. We conclude that CICR, the process responsible for SMH generation, represents a unique

  19. Facilitating Youth to Take Sustainability Actions: The Potential of Peer Education

    ERIC Educational Resources Information Center

    de Vreede, Catherine; Warner, Alan; Pitter, Robert

    2014-01-01

    Peer education is an understudied yet valuable strategy for sustainability educators in shifting youth to take action for sustainability. This case study conceptualizes the change process in facilitating youth to take sustainability actions, and explores the benefits, dynamics, and challenges of peer education as a strategy in facilitating change.…

  20. 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.

  1. Encoding of point of view during action observation in the local field potentials of macaque area F5.

    PubMed

    Caggiano, Vittorio; Giese, Martin; Thier, Peter; Casile, Antonino

    2015-02-01

    The discovery of mirror neurons compellingly shows that the monkey premotor area F5 is active not only during the execution but also during the observation of goal-directed motor acts. Previous studies have addressed the functioning of the mirror-neuron system at the single-unit level. Here, we tackled this research question at the network level by analysing local field potentials in area F5 while the monkey was presented with goal-directed actions executed by a human or monkey actor and observed either from a first-person or third-person perspective. Our analysis showed that rhythmic responses are not only present in area F5 during action observation, but are also modulated by the point of view. Observing an action from a subjective point of view produced significantly higher power in the low-frequency band (2-10 Hz) than observing the same action from a frontal view. Interestingly, an increase in power in the 2-10 Hz band was also produced by the execution of goal-directed motor acts. Independently of the point of view, action observation also produced a significant decrease in power in the 15-40 Hz band and an increase in the 60-100 Hz band. These results suggest that, depending on the point of view, action observation might activate different processes in area F5. Furthermore, they may provide information about the functional architecture of action perception in primates.

  2. Assessing the potential impact of water-based drill cuttings on deep-water calcareous red algae using species specific impact categories and measured oceanographic and discharge data.

    PubMed

    Nilssen, Ingunn; dos Santos, Francisco; Coutinho, Ricardo; Gomes, Natalia; Cabral, Marcelo Montenegro; Eide, Ingvar; Figueiredo, Marcia A O; Johnsen, Geir; Johnsen, Ståle

    2015-12-01

    The potential impact of drill cuttings on the two deep water calcareous red algae Mesophyllum engelhartii and Lithothamnion sp. from the Peregrino oil field was assessed. Dispersion modelling of drill cuttings was performed for a two year period using measured oceanographic and discharge data with 24 h resolution. The model was also used to assess the impact on the two algae species using four species specific impact categories: No, minor, medium and severe impact. The corresponding intervals for photosynthetic efficiency (ΦPSIImax) and sediment coverage were obtained from exposure-response relationship for photosynthetic efficiency as function of sediment coverage for the two algae species. The temporal resolution enabled more accurate model predictions as short-term changes in discharges and environmental conditions could be detected. The assessment shows that there is a patchy risk for severe impact on the calcareous algae stretching across the transitional zone and into the calcareous algae bed at Peregrino.

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

    PubMed

    Abee, T; Krockel, L; Hill, C

    1995-12-01

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

  4. 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

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

    PubMed

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

    2014-09-01

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

  6. RXP-E: A CX43-BINDING PEPTIDE THAT PREVENTS ACTION POTENTIAL PROPAGATION BLOCK

    PubMed Central

    Lewandowski, Rebecca; Procida, Kristina; Vaidyanathan, Ravi; Coombs, Wanda; Jalife, Jose; Nielsen, Morten S.; Taffet, Steven M.; Delmar, Mario

    2009-01-01

    Gap junctions (GJs) provide a low-resistance pathway for cardiac electrical propagation. The role of GJ regulation in arrhythmia is unclear, partly due to limited availability of pharmacological tools. Recently, we showed that a peptide called “RXP-E” binds to the carboxyl terminal of connexin43 (Cx43) and prevents chemically-induced uncoupling in Cx43-expressing N2a cells. Here, pull-down experiments show RXP-E binding to adult cardiac Cx43. Patch-clamp studies revealed that RXP-E prevented heptanol-induced and acidification-induced uncoupling in pairs of neonatal rat ventricular myocytes (NRVM’s). Separately, RXP-E was concatenated to a cytoplasmic transduction peptide for cytoplasmic translocation (CTP-RXP-E). The effect of RXP-E on action potential (AP) propagation was assessed by high resolution optical mapping in monolayers of NRVM’s, containing ~20% of randomly distributed myofibroblasts. In contrast to control experiments, when heptanol (2 mmol/L) was added to the superfusate of monolayers loaded with CTP-RXP-E, AP propagation was maintained, albeit at a slower velocity. Similarly, intracellular acidification (pHi=6.2) caused a loss of AP propagation in control monolayers; however, propagation was maintained in CTP-RXP-E treated cells, though at a slower rate. Patch clamp experiments revealed that RXP-E did not prevent heptanol-induced block of sodium currents, nor did it alter voltage dependence or amplitude of Kir2.1/Kir2.3 currents. RXP-E is the first synthetic molecule known to: (1) bind cardiac Cx43; (2) prevent heptanol and acidification-induced uncoupling of cardiac GJ’s and 3) preserve AP propagation among cardiac myocytes. RXP-E can be used to characterize the role of GJs in the function of multicellular systems, including the heart. PMID:18669919

  7. Impedance and electrically evoked compound action potential (ECAP) drop within 24 hours after cochlear implantation.

    PubMed

    Chen, Joshua Kuang-Chao; Chuang, Ann Yi-Chiun; Sprinzl, Georg Mathias; Tung, Tao-Hsin; Li, Lieber Po-Hung

    2013-01-01

    Previous animal study revealed that post-implantation electrical detection levels significantly declined within days. The impact of cochlear implant (CI) insertion on human auditory pathway in terms of impedance and electrically evoked compound action potential (ECAP) variation within hours after surgery remains unclear, since at this time frequency mapping can only commence weeks after implantation due to factors associated with wound conditions. The study presented our experiences with regards to initial switch-on within 24 hours, and thus the findings about the milieus inside cochlea within the first few hours after cochlear implantation in terms of impedance/ECAP fluctuations. The charts of fifty-four subjects with profound hearing impairment were studied. A minimal invasive approach was used for cochlear implantation, characterized by a small skin incision (≈ 2.5 cm) and soft techniques for cochleostomy. Impedance/ECAP was measured intro-operatively and within 24 hours post-operatively. Initial mapping within 24 hours post-operatively was performed in all patients without major complications. Impedance/ECAP became significantly lower measured within 24 hours post-operatively as compared with intra-operatively (p<0.001). There were no differences between pre-operative and post-operative threshold for air-conduction hearing. A significant drop of impedance/ECAP in one day after cochlear implantation was revealed for the first time in human beings. Mechanisms could be related to the restoration of neuronal sensitivity to the electrical stimulation, and/or the interaction between the matrix enveloping the electrodes and the electrical stimulation of the initial switch-on. Less wound pain/swelling and soft techniques both contributed to the success of immediate initial mapping, which implied a stable micro-environment inside the cochlea despite electrodes insertion. Our research invites further studies to correlate initial impedance/ECAP changes with long

  8. Impedance and Electrically Evoked Compound Action Potential (ECAP) Drop within 24 Hours after Cochlear Implantation

    PubMed Central

    Chen, Joshua Kuang-Chao; Chuang, Ann Yi-Chiun; Sprinzl, Georg Mathias; Tung, Tao-Hsin; Li, Lieber Po-Hung

    2013-01-01

    Previous animal study revealed that post-implantation electrical detection levels significantly declined within days. The impact of cochlear implant (CI) insertion on human auditory pathway in terms of impedance and electrically evoked compound action potential (ECAP) variation within hours after surgery remains unclear, since at this time frequency mapping can only commence weeks after implantation due to factors associated with wound conditions. The study presented our experiences with regards to initial switch-on within 24 hours, and thus the findings about the milieus inside cochlea within the first few hours after cochlear implantation in terms of impedance/ECAP fluctuations. The charts of fifty-four subjects with profound hearing impairment were studied. A minimal invasive approach was used for cochlear implantation, characterized by a small skin incision (≈2.5 cm) and soft techniques for cochleostomy. Impedance/ECAP was measured intro-operatively and within 24 hours post-operatively. Initial mapping within 24 hours post-operatively was performed in all patients without major complications. Impedance/ECAP became significantly lower measured within 24 hours post-operatively as compared with intra-operatively (p<0.001). There were no differences between pre-operative and post-operative threshold for air-conduction hearing. A significant drop of impedance/ECAP in one day after cochlear implantation was revealed for the first time in human beings. Mechanisms could be related to the restoration of neuronal sensitivity to the electrical stimulation, and/or the interaction between the matrix enveloping the electrodes and the electrical stimulation of the initial switch-on. Less wound pain/swelling and soft techniques both contributed to the success of immediate initial mapping, which implied a stable micro-environment inside the cochlea despite electrodes insertion. Our research invites further studies to correlate initial impedance/ECAP changes with long

  9. 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

  10. Spatial variation of compound muscle action potentials across human gastrocnemius medialis.

    PubMed

    Vieira, Taian M; Botter, Alberto; Minetto, Marco A; Hodson-Tole, Emma F

    2015-09-01

    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.

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

    PubMed

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

    2016-08-01

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

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

    PubMed

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

    2013-01-01

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

  13. 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.

  14. A Novel Computational Model of the Human Ventricular Action Potential and Ca Transient

    PubMed Central

    Grandi, Eleonora; Pasqualini, Francesco S.; Bers, Donald M.

    2009-01-01

    We have developed a detailed mathematical model for Ca handling and ionic currents in the human ventricular myocyte. Our aims were to: 1) simulate basic excitation-contraction coupling phenomena; 2) use realistic repolarizing K current densities; 3) reach steady-state. The model relies on the framework of the rabbit myocyte model previously developed by our group, with subsarcolemmal and junctional compartments where ion channels sense higher [Ca] vs. bulk cytosol. Ion channels and transporters have been modeled on the basis of the most recent experimental data from human ventricular myocytes. Rapidly and slowly inactivating components of Ito have been formulated to differentiate between endocardial and epicardial myocytes. Transmural gradients of Ca handling proteins and Na pump were also simulated. The model has been validated against a wide set of experimental data including action potential duration (APD) adaptation and restitution, frequency-dependent increase in Ca transient peak and [Na]i. Interestingly, Na accumulation at fast heart rate is a major determinant of APD shortening, via outward shifts in Na pump and Na-Ca exchange currents. We investigated the effects of blocking K currents on APD and repolarization reserve: IKs block does not affect the former and slightly reduces the latter; IK1 blockade modestly increases APD and more strongly reduces repolarization reserve; IKr blockers significantly prolong APD, an effect exacerbated as pacing frequency is decreased, in good agreement with experimental results in human myocytes. We conclude that this model provides a useful framework to explore excitation-contraction coupling mechanisms and repolarization abnormalities at the single myocyte level. PMID:19835882

  15. Vaginal Discharge

    MedlinePlus

    ... also be on the lookout for symptoms of yeast infections, bacterial vaginosis and trichomoniasis, 3 infections that ... cause changes in your vaginal discharge. Signs of yeast infections White, cottage cheese-like discharge Swelling and ...

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

    PubMed

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

    2011-02-01

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

  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. 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

  19. Bone marrow transplant - discharge

    MedlinePlus

    Transplant - bone marrow - discharge; Stem cell transplant - discharge; Hematopoietic stem cell transplant - discharge; Reduced intensity; Non-myeloablative transplant - discharge; Mini transplant - discharge; Allogenic bone marrow transplant - ...

  20. Pediatric heart surgery - discharge

    MedlinePlus

    Congenital heart surgery - discharge; Patent ductus arteriosus ligation - discharge; Hypoplastic left heart repair - discharge; Tetralogy of Fallot repair - discharge; Coarctation of the aorta repair - discharge; ...

  1. Deep vein thrombosis - discharge

    MedlinePlus

    DVT - discharge; Blood clot in the legs - discharge; Thromboembolism - discharge; Venous thromboembolism - deep vein thrombosis; Post-phlebitic syndrome - discharge; Post-thrombotic syndrome - discharge

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

    PubMed

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

    2016-01-01

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

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

    PubMed

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

    2016-01-01

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

  4. Hollow Electrode Discharge Triodes

    NASA Astrophysics Data System (ADS)

    Schoenbach, K. H.; Peterkin, F. E.; Tessnow, T.

    1996-10-01

    The current through a direct current micro-hollow electrode (electrode hole diameter: 0.7 mm) discharge in argon was shown to be controllable by means of a third, external electrode placed close to the cathode opening. By increasing the potential of the positively biased control electrode from zero to 30 V the discharge current could be linearly reduced from 5 μA to 0.75 μA, at a discharge voltage of 300 V. The current-voltage characteristic of the micro-hollow electrode discharge was found to have a positive slope, allowing parallel discharge operation without ballast. By drilling holes through a metal-plated, dielectric film, an array of hollow electrode discharges could be generated. It was shown that each discharge responds individually to variations in the potential of the corresponding external control electrode. The simplicity of the electrode configuration and the possibility of linear, electrical control of the individual discharge currents offers the possibility to use these triode arrays in addressable flat panel displays (patent pending).

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

    ERIC Educational Resources Information Center

    Merç, Ali

    2015-01-01

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

  6. Action Learning in Higher Education: An Investigation of Its Potential to Develop Professional Capability

    ERIC Educational Resources Information Center

    Lizzio, Alf; Wilson, Keithia

    2004-01-01

    This study investigated the extent to which a course, designed using peer and action learning principles to function as an 'on campus practicum', can develop the professional capabilities of students. As part of their formal coursework, third year behavioural science students, functioning as 'student consultants', entered into a…

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

    PubMed

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

    2007-03-15

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

  8. Investigation on the Cyclability of Lithium-Oxygen Cells in a Confined Potential Window using Cathodes with Pre-filled Discharge Products.

    PubMed

    Geng, Dongsheng; Ding, Ning; Hor, T S Andy; Chien, Sheau Wei; Liu, Zhaolin; Zong, Yun

    2015-10-01

    With new chemistry and advantageous configuration, the lithium-oxygen (Li-O2) battery promises a much higher specific energy than traditional lithium-ion batteries. The limited understanding on the complicated battery reactions therein, however, has become a major bottleneck of its development for applications requiring a high energy efficiency and long cycle-life. Herein, in a confined potential window with negligible electrolyte degradation, we studied the rechargeability of Li-O2 cathodes with pre-filled well-defined discharge products of Li2O2, Li2CO3, LiOH, or their combinations. Our results suggest Li2CO3 as the most difficult species to be electrochemically decomposed among the three lithium compounds, whereas the presence of LiOH notably increases the initial charge potential. The clearly visible difference in the charge behavior and cycling stability of these artificially "discharged" electrodes provides a guideline for the development of future high-performance Li-O2 batteries. PMID:26011604

  9. Surface treatment by electric discharge machining of Ti-6Al-4V alloy for potential application in orthopaedics.

    PubMed

    Harcuba, Petr; Bačáková, Lucie; Stráský, Josef; Bačáková, Markéta; Novotná, Katarína; Janeček, Miloš

    2012-03-01

    This study investigated the properties of Ti-6Al-4V alloy after surface treatment by the electric discharge machining (EDM) process. The EDM process with high peak currents proved to induce surface macro-roughness and to cause chemical changes to the surface. Evaluations were made of the mechanical properties by means of tensile tests, and of surface roughness for different peak currents of the EDM process. The EDM process with peak current of 29 A was found to induce sufficient surface roughness, and to have a low adverse effect on tensile properties. The chemical changes were studied by scanning electron microscopy equipped with an energy dispersive X-ray analyser (EDX). The surface of the benchmark samples was obtained by plasma-spraying a titanium dioxide coating. An investigation of the biocompatibility of the surface-treated Ti-6Al-4V samples in cultures of human osteoblast-like MG 63 cells revealed that the samples modified by EDM provided better substrates for the adhesion, growth and viability of MG 63 cells than the TiO2 coated surface. Thus, EDM treatment can be considered as a promising surface modification to orthopaedic implants, in which good integration with the surrounding bone tissue is required.

  10. Influence of river discharge patterns on the hydrodynamics and potential contaminant dispersion in the Douro estuary (Portugal).

    PubMed

    Azevedo, Isabel C; Bordalo, Adriano A; Duarte, Pedro M

    2010-05-01

    Freshwater input to estuaries is a fundamental feature of these ecosystems, which may be profoundly altered by river damming as human needs for water consumption, irrigation or energy production increase. The Douro estuary is limited upstream by a dam since 1985, which reduced its length by ca. 60%. Freshwater inputs to the estuary are now irregular and greatly dependent on hydroelectric power demand; values ranging from zero to over 1000m(3)s(-1), in a matter of hours, especially in summer are common. In the present study, a three-dimensional hydrodynamic model was applied to the Douro estuary. The model was calibrated and validated against water elevation, current velocity, salinity and temperature data. Thereafter, it was used to analyse the effects of different flow regimes and magnitudes on estuarine hydrodynamics and contaminant dispersion. Results obtained suggest that the highly variable flow regimes, currently observed in the Douro, tend to reduce water column stratification and to enhance seawater intrusion, when compared with flow discharges of similar average magnitude, but lower variability. Stable flows seem to be the most effective in dispersing contaminants eventually introduced into the estuary through its small river tributaries. Overall results suggest that flow management may have important effects on estuarine hydrodynamics through non-linear interactions between flow magnitude and variability.

  11. Determining electrically evoked compound action potential thresholds: A comparison of computer versus human analysis methods

    PubMed Central

    Glassman, E. Katelyn; Hughes, Michelle L.

    2012-01-01

    Objectives Current cochlear implants (CIs) have telemetry capabilities for measuring the electrically evoked compound action potential (ECAP). Neural Response Telemetry (NRT™; Cochlear) and Neural Response Imaging (NRI; Advanced Bionics [AB]) can measure ECAP responses across a range of stimulus levels to obtain an amplitude growth function. Software-specific algorithms automatically mark the leading negative peak, N1, and the following positive peak/plateau, P2, and apply linear regression to estimate ECAP threshold. Alternatively, clinicians may apply expert judgments to modify the peak markers placed by the software algorithms, and/or use visual detection to identify the lowest level yielding a measurable ECAP response. The goals of this study were to: (1) assess the variability between human and computer decisions for (a) marking N1 and P2, and (b) determination of linear regression threshold (LRT) and visual detection threshold (VDT); and (2) compare LRT and VDT methods within and across human and computer decision methods. Design ECAP amplitude growth functions were measured for three electrodes in each of 20 ears (10 Cochlear Nucleus® 24RE/CI512, and 10 AB CII/90K). LRT, defined as the current level yielding an ECAP with zero amplitude, was calculated for both computer- (C-LRT) and human-picked peaks (H-LRT). VDT, defined as the lowest level resulting in a measurable ECAP response, was also calculated for both computer- (C-VDT) and human-picked peaks (H-VDT). Because NRI assigns peak markers to all waveforms but does not include waveforms with amplitudes less than 20 μV in its regression calculation, C-VDT for AB subjects was defined as the lowest current level yielding an amplitude ≥20 μV. Results Overall, there were significant correlations between human and computer decisions for peak-marker placement, LRT, and VDT for both manufacturers (r = 0.78 to 1.00, p < 0.001). For Cochlear devices, LRT and VDT correlated equally well for both computer- and

  12. [Hardware Implementation of Numerical Simulation Function of Hodgkin-Huxley Model Neurons Action Potential Based on Field Programmable Gate Array].

    PubMed

    Wang, Jinlong; Lu, Mai; Hu, Yanwen; Chen, Xiaoqiang; Pan, Qiangqiang

    2015-12-01

    Neuron is the basic unit of the biological neural system. The Hodgkin-Huxley (HH) model is one of the most realistic neuron models on the electrophysiological characteristic description of neuron. Hardware implementation of neuron could provide new research ideas to clinical treatment of spinal cord injury, bionics and artificial intelligence. Based on the HH model neuron and the DSP Builder technology, in the present study, a single HH model neuron hardware implementation was completed in Field Programmable Gate Array (FPGA). The neuron implemented in FPGA was stimulated by different types of current, the action potential response characteristics were analyzed, and the correlation coefficient between numerical simulation result and hardware implementation result were calculated. The results showed that neuronal action potential response of FPGA was highly consistent with numerical simulation result. This work lays the foundation for hardware implementation of neural network. PMID:27079105

  13. Ventricular filling slows epicardial conduction and increases action potential duration in an optical mapping study of the isolated rabbit heart

    NASA Technical Reports Server (NTRS)

    Sung, Derrick; Mills, Robert W.; Schettler, Jan; Narayan, Sanjiv M.; Omens, Jeffrey H.; McCulloch, Andrew D.; McCullough, A. D. (Principal Investigator)

    2003-01-01

    INTRODUCTION: Mechanical stimulation can induce electrophysiologic changes in cardiac myocytes, but how mechanoelectric feedback in the intact heart affects action potential propagation remains unclear. METHODS AND RESULTS: Changes in action potential propagation and repolarization with increased left ventricular end-diastolic pressure from 0 to 30 mmHg were investigated using optical mapping in isolated perfused rabbit hearts. With respect to 0 mmHg, epicardial strain at 30 mmHg in the anterior left ventricle averaged 0.040 +/- 0.004 in the muscle fiber direction and 0.032 +/- 0.006 in the cross-fiber direction. An increase in ventricular loading increased average epicardial activation time by 25%+/- 3% (P < 0.0001) and correspondingly decreased average apparent surface conduction velocity by 16%+/- 7% (P = 0.007). Ventricular loading did not significantly alter action potential duration at 20% repolarization (APD20) but did at 80% repolarization (APD80), from 179 +/- 7 msec to 207 +/- 5 msec (P < 0.0001). The dispersion of APD20 was decreased with loading from 19 +/- 2 msec to 13 +/- 2 msec (P = 0.024), whereas the dispersion of APD80 was not significantly changed. These electrophysiologic changes with ventricular loading were not affected by the nonspecific stretch-activated channel blocker streptomycin (200 microM) and were not attributable to changes in myocardial perfusion or the presence of an electromechanical decoupling agent (butanedione monoxime) during optical mapping. CONCLUSION: Acute loading of the left ventricle of the isolated rabbit heart decreased apparent epicardial conduction velocity and increased action potential duration by a load-dependent mechanism that may not involve stretch-activated channels.

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

    NASA Astrophysics Data System (ADS)

    Salzberg, Brian M.

    2008-03-01

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

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

    PubMed

    Herde, Michel K; Herbison, Allan E

    2015-11-01

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

  16. Galvanic action between MnO/sub 2/-metal couples and its effect on the discharge of Li/MnO/sub 2/ cells

    SciTech Connect

    Fleischer, N.A.; Ekern, R.J.

    1985-01-01

    Corrosion of the case material seems to be the most likely cause of the galvanic activity measured in these experiments. Changes of the inner surface of the case due to the accumulation of corrosion products might interfere with contact to the MnO/sub 2/, which could account for the higher predischarge impedance levels for case materials with larger GCC. The simplest explanation is that the additional impedance contributed to the cell by the corrosion process is additive with the increase in impedance due to the lithium insertion process. Thus, cells built with materials exhibiting a high GCC reach the 50..cap omega.. impedance cutoff sooner than cells built with corrosion resistant case materials, e.g., Shomac 30-2. High cell impedance and the degraded contact between the MnO/sub 2/ and the case can also be used to explain the lower discharge capacity generally found in cells built with materials having high levels of GCC. The lower capacity is due to slope of the discharge curve which shortens the discharge time.

  17. Role of gap junction channel in the development of beat-to-beat action potential repolarization variability and arrhythmias.

    PubMed

    Magyar, Janos; Banyasz, Tamas; Szentandrassy, Norbert; Kistamas, Kornel; Nanasi, Peter P; Satin, Jonathan

    2015-01-01

    The short-term beat-to-beat variability of cardiac action potential duration (SBVR) occurs as a random alteration of the ventricular repolarization duration. SBVR has been suggested to be more predictive of the development of lethal arrhythmias than the action potential prolongation or QT prolongation of ECG alone. The mechanism underlying SBVR is not completely understood but it is known that SBVR depends on stochastic ion channel gating, intracellular calcium handling and intercellular coupling. Coupling of single cardiomyocytes significantly decreases the beat-to-beat changes in action potential duration (APD) due to the electrotonic current flow between neighboring cells. The magnitude of this electrotonic current depends on the intercellular gap junction resistance. Reduced gap junction resistance causes greater electrotonic current flow between cells, and reduces SBVR. Myocardial ischaemia (MI) is known to affect gap junction channel protein expression and function. MI increases gap junction resistance that leads to slow conduction, APD and refractory period dispersion, and an increase in SBVR. Ultimately, development of reentry arrhythmias and fibrillation are associated post-MI. Antiarrhythmic drugs have proarrhythmic side effects requiring alternative approaches. A novel idea is to target gap junction channels. Specifically, the use of gap junction channel enhancers and inhibitors may help to reveal the precise role of gap junctions in the development of arrhythmias. Since cell-to-cell coupling is represented in SBVR, this parameter can be used to monitor the degree of coupling of myocardium.

  18. Amplitude of sensory nerve action potential in early stage diabetic peripheral neuropathy: an analysis of 500 cases.

    PubMed

    Zhang, Yunqian; Li, Jintao; Wang, Tingjuan; Wang, Jianlin

    2014-07-15

    Early diagnosis of diabetic peripheral neuropathy is important for the successful treatment of diabetes mellitus. In the present study, we recruited 500 diabetic patients from the Fourth Affiliated Hospital of Kunming Medical University in China from June 2008 to September 2013: 221 cases showed symptoms of peripheral neuropathy (symptomatic group) and 279 cases had no symptoms of peripheral impairment (asymptomatic group). One hundred healthy control subjects were also recruited. Nerve conduction studies revealed that distal motor latency was longer, sensory nerve conduction velocity was slower, and sensory nerve action potential and amplitude of compound muscle action potential were significantly lower in the median, ulnar, posterior tibial and common peroneal nerve in the diabetic groups compared with control subjects. Moreover, the alterations were more obvious in patients with symptoms of peripheral neuropathy. Of the 500 diabetic patients, neural conduction abnormalities were detected in 358 cases (71.6%), among which impairment of the common peroneal nerve was most prominent. Sensory nerve abnormality was more obvious than motor nerve abnormality in the diabetic groups. The amplitude of sensory nerve action potential was the most sensitive measure of peripheral neuropathy. Our results reveal that varying degrees of nerve conduction changes are present in the early, asymptomatic stage of diabetic peripheral neuropathy.

  19. Coupled iterated map models of action potential dynamics in a one-dimensional cable of cardiac cells

    NASA Astrophysics Data System (ADS)

    Wang, Shihong; Xie, Yuanfang; Qu, Zhilin

    2008-05-01

    Low-dimensional iterated map models have been widely used to study action potential dynamics in isolated cardiac cells. Coupled iterated map models have also been widely used to investigate action potential propagation dynamics in one-dimensional (1D) coupled cardiac cells, however, these models are usually empirical and not carefully validated. In this study, we first developed two coupled iterated map models which are the standard forms of diffusively coupled maps and overcome the limitations of the previous models. We then determined the coupling strength and space constant by quantitatively comparing the 1D action potential duration profile from the coupled cardiac cell model described by differential equations with that of the coupled iterated map models. To further validate the coupled iterated map models, we compared the stability conditions of the spatially uniform state of the coupled iterated maps and those of the 1D ionic model and showed that the coupled iterated map model could well recapitulate the stability conditions, i.e. the spatially uniform state is stable unless the state is chaotic. Finally, we combined conduction into the developed coupled iterated map model to study the effects of coupling strength on wave stabilities and showed that the diffusive coupling between cardiac cells tends to suppress instabilities during reentry in a 1D ring and the onset of discordant alternans in a periodically paced 1D cable.

  20. 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.

  1. CO-AXIAL DISCHARGES

    DOEpatents

    Luce, J.S.; Smith, L.P.

    1960-11-22

    A method and apparatus are given for producing coaxial arc discharges in an evacuated enclosure and within a strong, confining magnetic field. The arcs are maintained at a high potential difference. Electrons will diffuse to the more positive arc from the negative arc, and positive ions will diffuse from the more positive arc to the negative arc. Coaxial arc discharges have the advantage that ions which return to strike the positive arc discharge will lose no energy since they do not strike a solid wall or electrode. Those discharges are useful in confining an ionized plasma between the discharges, and have the advantage of preventing impurities from the walls of the enclosure from entering ihe plasma area because of the arc barrier set up bv the cylindrical outer arc.

  2. Co-axial discharges

    DOEpatents

    Luce, J. S.; Smith, L. P.

    1960-11-22

    An apparatus is described for producing coaxial arc discharges in an evacuated enclosure and within a strong, confining magnetic field. The arcs are maintained at a high potential difference. Electrons diffuse to the more positive arc from the negative arc, and positive ions diffuse from the more positive arc to the negative arc. Coaxial arc discharges have the advantuge that ions that return to strike the positive arc discharge will lose no energy since they do not strike a solid wall or electrode. These discharges are useful in confining an ionized plasma between the discharges and have the advantage of preventing impurities from the walls of the enclosure from entering the plasma area because of the arc barrier set up by the cylindrical outer arc. (auth)

  3. Diosgenin, 4-hydroxyisoleucine, and fiber from fenugreek: mechanisms of actions and potential effects on metabolic syndrome.

    PubMed

    Fuller, Scott; Stephens, Jacqueline M

    2015-03-01

    Metabolic syndrome and its complications continue to rise in prevalence and show no signs of abating in the immediate future. Therefore, the search for effective treatments is a high priority in biomedical research. Products derived from botanicals have a time-honored history of use in the treatment of metabolic diseases including type 2 diabetes. Trigonella foenum-graecum, commonly known as fenugreek, is an annual herbaceous plant that has been a staple of traditional herbal medicine in many cultures. Although fenugreek has been studied in both clinical and basic research settings, questions remain about its efficacy and biologic mechanisms of action. Diosgenin, 4-hydroxyisoleucine, and the fiber component of the plant are the most intensively studied bioactive constituents present in fenugreek. These compounds have been demonstrated to exert beneficial effects on several physiologic markers including glucose tolerance, inflammation, insulin action, liver function, blood lipids, and cardiovascular health. Although insights into the molecular mechanisms underlying the favorable effects of fenugreek have been gained, we still do not have definitive evidence establishing its role as a therapeutic agent in metabolic disease. This review aims to summarize the currently available evidence on the physiologic effects of the 3 best-characterized bioactive compounds of fenugreek, with particular emphasis on biologic mechanisms of action relevant in the context of metabolic syndrome. PMID:25770257

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

    NASA Astrophysics Data System (ADS)

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

    2016-05-01

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

  5. A quantitative evaluation of the magnetic field generated by a CA3 pyramidal cell at EPSP and action potential stages.

    PubMed

    Sakatani, Seiichi; Hirose, Akira

    2002-04-01

    We evaluate quantitatively which behavioral stage dominantly generates magnetic field adjacent to a CA3 pyramidal cell by using a compartmental model with dendrites and an axon. Generally speaking, there are four stages in the potential behavior, i.e., excitatory and inhibitory postsynaptic potential, firing action potential, bursting action potential, if any, and after hyperpolarization potential stages. Calculated magnetic field also consists of corresponding four stages. We find, first, the dominant origin of the peaks of the magnetic field is counter propagating pulses at the firing and bursting stage at basal and apical dendrites. Second, the amplitude of the magnetic field changes to a great extent by the cancellation timing of the apical- and basal-originating fields depending on the calcium ionic channel spikes. Third, the field generated by the current flowing through the axon is significant enough when the temporal resolution of the measurement system becomes high. The results predict that the magnetic-field waveform measured in physiological experiments represents the dendritic configurations, channel density distributions, and bursting characteristics. These facts enable new investigations of neuronal activities in more detail through the observation of the magnetic-field waveform.

  6. INHIBITION OF BRAIN CHOLINESTERASE AND THE PHOTIC AFTER DISCHARGE OF FLASH EVOKED POTENTIALS PRODUCED BY CARBARYL IN LONG EVANS RATS.

    EPA Science Inventory

    Carbaryl is a widely used N-methyl carbamate pesticide that acts by inhibiting cholinesterases (ChE), which may lead to cholinergic toxicity. Flash evoked potentials (FEPs) are a neurophysiological response often used to detect central nervous system (CNS) changes following expos...

  7. Dissociating action inhibition, conflict monitoring and sensory mismatch into independent components of event related potentials in GO/NOGO task.

    PubMed

    Kropotov, Juri D; Ponomarev, Valery A; Hollup, Stig; Mueller, Andreas

    2011-07-15

    The anterior N2 and P3 waves of event related potentials (ERPs) in the GO/NOGO paradigm in trials related to preparatory set violations in previous studies were inconsistently associated either with action inhibition or conflict monitoring operations. In the present study a paired stimulus GO/NOGO design was used in order to experimentally control the preparatory sets. Three variants of the same stimulus task manipulated sensory mismatch, action inhibition and conflict monitoring operations by varying stimulus-response associations. The anterior N2 and P3 waves were decomposed into components by means of independent component analysis (ICA). The ICA was performed on collection of 114 individual ERPs in the three experimental conditions. Three of the independent components were selectively affected by the task manipulations indicating association of these components with sensory mismatch, action inhibition and conflict monitoring operations. According to sLORETA the sensory mismatch component was generated in the left and right temporal areas, the action suppression component was generated in the supplementary motor cortex, and the conflict monitoring component was generated in the anterior cingulate cortex.

  8. Potential of rapid adjustment of brief interceptive action using predicted information.

    PubMed

    Ikudome, Sachi; Nakamoto, Hiroki; Yotani, Kengo; Unenaka, Satoshi; Mori, Shiro

    2015-07-01

    Interceptive actions, such as hitting a ball in baseball or tennis, feature a moving target whose parameters (i.e., velocity or trajectory) differ across trials. This means that players are required to make rapid trial-by-trial adjustments. The purpose of this study was to determine whether a brief interceptive action could be adjusted using predicted sensory consequence of movement (pSCM) information, even under severe time constraints where the participants could not adjust their movement using only visual feedback. Participants performed an interceptive action for targets with two different velocities with different occurrence probabilities (20%, 50%, and 80%). Prior to movement onset, we applied transcranial magnetic stimulation (TMS) to the supplementary motor area (SMA), as TMS of the SMA is known to disrupt pSCM activity. We hypothesized that if pSCM information were used to adjust the motor parameters of a brief interception, then TMS would significantly increase the constant temporal error (i.e., the difference between the sum of reaction time and movement time and the total target visible time) for a target velocity with a low probability (20%). This hypothesis is based on the previous findings that the pSCM plays an important role in the adjustment of relatively brief interception. We found that while interceptions that lasted about 250 ms after movement onset were unaffected, interceptions that lasted about 350 ms after movement onset could be influenced by TMS. However, TMS interfered with performance provided that the delivery of the pulse occurred 100 ms before movement onset. This finding suggests that pSCM information that is used for a rapid adjustment is generated only in that specific time interval. PMID:26010202

  9. Potential of rapid adjustment of brief interceptive action using predicted information.

    PubMed

    Ikudome, Sachi; Nakamoto, Hiroki; Yotani, Kengo; Unenaka, Satoshi; Mori, Shiro

    2015-07-01

    Interceptive actions, such as hitting a ball in baseball or tennis, feature a moving target whose parameters (i.e., velocity or trajectory) differ across trials. This means that players are required to make rapid trial-by-trial adjustments. The purpose of this study was to determine whether a brief interceptive action could be adjusted using predicted sensory consequence of movement (pSCM) information, even under severe time constraints where the participants could not adjust their movement using only visual feedback. Participants performed an interceptive action for targets with two different velocities with different occurrence probabilities (20%, 50%, and 80%). Prior to movement onset, we applied transcranial magnetic stimulation (TMS) to the supplementary motor area (SMA), as TMS of the SMA is known to disrupt pSCM activity. We hypothesized that if pSCM information were used to adjust the motor parameters of a brief interception, then TMS would significantly increase the constant temporal error (i.e., the difference between the sum of reaction time and movement time and the total target visible time) for a target velocity with a low probability (20%). This hypothesis is based on the previous findings that the pSCM plays an important role in the adjustment of relatively brief interception. We found that while interceptions that lasted about 250 ms after movement onset were unaffected, interceptions that lasted about 350 ms after movement onset could be influenced by TMS. However, TMS interfered with performance provided that the delivery of the pulse occurred 100 ms before movement onset. This finding suggests that pSCM information that is used for a rapid adjustment is generated only in that specific time interval.

  10. Effects of muscle action type with equal impulse of conditioning activity on postactivation potentiation.

    PubMed

    Bogdanis, Gregory C; Tsoukos, Athanasios; Veligekas, Panagiotis; Tsolakis, Charilaos; Terzis, Gerasimos

    2014-09-01

    This study investigated the effects of muscle action type during conditioning activity (half-squat) on subsequent vertical jump performance. Fourteen track and field athletes (relative half-squat of 2.3 ± 0.3 times their body weight) completed 4 main trials in a randomized and counterbalanced order 5-7 days apart: (a) concentric (CON) half-squats: 7.5 ± 1.2 repetitions against 90% of 1 repetition maximum (1RM), (b) eccentric (ECC) half-squats: 9.3 ± 1.5 repetitions against 70% of 1RM, and (c) 3 sets of 3-second maximal isometric (ISO) half-squats, (d) a control (CTRL) trial, where subjects rested for 10 minutes. The number of repetitions in CON and ECC was adjusted so that the impulse of the vertical ground reaction force was similar to ISO. Countermovement vertical jump (CMJ) performance was evaluated for 21 minutes after each main trial. Countermovement vertical jump performance in ISO was higher than CTRL from the second to the 10th minute of recovery, whereas CMJ performance in ECC was higher than CTRL from the sixth and 10th minute of recovery. Analysis of the peak individual responses revealed an increase in CMJ performance compared with baseline only in ISO (3.0 ± 1.2%; p = 0.045), whereas no significant increases were observed in ECC and CON. Peak CMJ performance for all subjects in ISO and ECC was achieved within 2-10 minutes after the conditioning muscle actions. Isometric were more effective than CON and ECC muscle actions in increasing explosive leg performance when the impulse of the ground reaction force of the conditioning exercise was equated.

  11. POTENTIATION OF THE ACTION OF BRADYKININ ON SMOOTH MUSCLE BY CHYMOTRYPSIN, CHYMOTRYPSINOGEN AND TRYPSIN.

    PubMed

    EDERY, H

    1964-04-01

    Chymotrypsin, chymotrypsinogen and trypsin sensitized the guinea-pig isolated ileum and rat isolated uterus preparations to the action of bradykinin, whilst the responses to histamine, acetylcholine and 5-hydroxytryptamine were unaffected. Chymotrypsin caused a quick contraction of the guinea-pig ileum which was abolished by mepyramine and therefore probably mediated by histamine. Trypsin contracted the rat uterus as well as the guinea-pig ileum; the latter contraction was slow, resistant to mepyramine and gave rise to tachyphylaxis. It is suggested that isolated smooth muscle preparations should be treated with chymotrypsin for use in the estimation of minute amounts of bradykinin.

  12. Conservation laws of wave action and potential enstrophy for Rossby waves in a stratified atmosphere

    NASA Technical Reports Server (NTRS)

    Straus, D. M.

    1983-01-01

    The evolution of wave energy, enstrophy, and wave motion for atmospheric Rossby waves in a variable mean flow are discussed from a theoretical and pedagogic standpoint. In the absence of mean flow gradients, the wave energy density satisfies a local conservation law, with the appropriate flow velocity being the group velocity. In the presence of mean flow variations, wave energy is not conserved, but wave action is, provided the mean flow is independent of longitude. Wave enstrophy is conserved for arbitrary variations of the mean flow. Connections with Eliassen-Palm flux are also discussed.

  13. Conservation laws of wave action and potential enstrophy for Rossby waves in a stratified atmosphere

    NASA Technical Reports Server (NTRS)

    Straus, D. M.

    1983-01-01

    The evolution of wave energy, enstrophy, and wave motion for atmospheric Rossby waves in a variable mean flow are discussed from a theoretical and pedagogic standpoint. In the absence of mean flow gradients, the wave energy density satisfies a local conservation law, with the appropriate flow velocity being the group velocity. In the presence of mean flow variations, wave energy is not conserved, but wave action is, provided the mean flow is independent of longitude. Wave enstrophy is conserved for arbitrary variations of the mean flow. Connections with Eiiassen-Palm flux are also discussed.

  14. Overcoming photodamage in second-harmonic generation microscopy: real-time optical recording of neuronal action potentials.

    PubMed

    Sacconi, L; Dombeck, D A; Webb, W W

    2006-02-28

    Second-harmonic generation (SHG) has proven essential for the highest-resolution optical recording of membrane potential (Vm) in intact specimens. Here, we demonstrate single-trial SHG recordings of neuronal somatic action potentials and quantitative recordings of their decay with averaging at multiple sites during propagation along branched neurites at distances up to 350 mum from the soma. We realized these advances by quantifying, analyzing, and thereby minimizing the dynamics of photodamage (PD), a frequent limiting factor in the optical imaging of biological preparations. The optical signal and the PD during SHG imaging of stained cultured Aplysia neurons were examined with intracellular electrode recordings monitoring the resting Vm variations induced by laser-scanning illumination. We found that the PD increased linearly with the dye concentration but grew with the cube of illumination intensity, leading to unanticipated optimization procedures to minimize PD. The addition of appropriate antioxidants in conjunction with an observed Vm recovery after termination of laser scanning further refined the imaging criteria for minimization and control of PD during SHG recording of action potentials. With these advances, the potential of SHG as an effective optical tool for neuroscience investigations is being realized.

  15. Comparison of genetically encoded calcium indicators for monitoring action potentials in mammalian brain by two-photon excitation fluorescence microscopy

    PubMed Central

    Podor, Borbala; Hu, Yi-ling; Ohkura, Masamichi; Nakai, Junichi; Croll, Roger; Fine, Alan

    2015-01-01

    Abstract. Imaging calcium transients associated with neuronal activity has yielded important insights into neural physiology. Genetically encoded calcium indicators (GECIs) offer conspicuous potential advantages for this purpose, including exquisite targeting. While the catalogue of available GECIs is steadily growing, many newly developed sensors that appear promising in vitro or in model cells appear to be less useful when expressed in mammalian neurons. We have, therefore, evaluated the performance of GECIs from two of the most promising families of sensors, G-CaMPs [Nat. Biotechnol. 19(2), 137–141 (2001)11175727] and GECOs [Science 333(6051), 1888–1891 (2011)21903779], for monitoring action potentials in rat brain. Specifically, we used two-photon excitation fluorescence microscopy to compare calcium transients detected by G-CaMP3; GCaMP6f; G-CaMP7; Green-GECO1.0, 1.1 and 1.2; Blue-GECO; Red-GECO; Rex-GECO0.9; Rex-GECO1; Carmine-GECO; Orange-GECO; and Yellow-GECO1s. After optimizing excitation wavelengths, we monitored fluorescence signals associated with increasing numbers of action potentials evoked by current injection in CA1 pyramidal neurons in rat organotypic hippocampal slices. Some GECIs, particularly Green-GECO1.2, GCaMP6f, and G-CaMP7, were able to detect single action potentials with high reliability. By virtue of greatest sensitivity and fast kinetics, G-CaMP7 may be the best currently available GECI for monitoring calcium transients in mammalian neurons. PMID:26158004

  16. Modulatory action of acetylcholine on the Na+-dependent action potentials in Kenyon cells isolated from the mushroom body of the cricket brain.

    PubMed

    Terazima, E; Yoshino, M

    2010-12-01

    Kenyon cells, intrinsic neurons of the insect mushroom body, have been assumed to be a site of conditioning stimulus (CS) and unconditioned stimulus (US) association in olfactory learning and memory. Acetylcholine (ACh) has been implicated to be a neurotransmitter mediating CS reception in Kenyon cells, causing rapid membrane depolarization via nicotinic ACh receptors. However, the long-term effects of ACh on the membrane excitability of Kenyon cells are not fully understood. In this study, we examined the effects of ACh on Na(+) dependent action potentials (Na(+) spikes) elicited by depolarizing current injection and on net membrane currents under the voltage clamp condition in Kenyon cells isolated from the mushroom body of the cricket Gryllus bimaculatus. Current-clamp studies using amphotericin B perforated-patch recordings showed that freshly dispersed cricket Kenyon cells could produce repetitive Na(+) spikes in response to prolonged depolarizing current injection. Bath application of ACh increased both the instantaneous frequency and the amplitudes of Na(+) spikes. This excitatory action of ACh on Kenyon cells is attenuated by the pre-treatment of the cells with the muscarinic receptor antagonists, atropine and scopolamine, but not by the nicotinic receptor antagonist mecamylamine. Voltage-clamp studies further showed that bath application of ACh caused an increase in net inward currents that are sensitive to TTX, whereas outward currents were decreased by this treatment. These results indicate that in order to mediate CS, ACh may modulate the firing properties of Na(+) spikes of Kenyon cells through muscarinic receptor activation, thus increasing Na conductance and decreasing K conductance.

  17. The potential for multi-disciplinary primary health care services to take action on the social determinants of health: actions and constraints

    PubMed Central

    2013-01-01

    Background The Commission on the Social Determinants of Health and the World Health Organization have called for action to address the social determinants of health. This paper considers the extent to which primary health care services in Australia are able to respond to this call. We report on interview data from an empirical study of primary health care centres in Adelaide and Alice Springs, Australia. Methods Sixty-eight interviews were held with staff and managers at six case study primary health care services, regional health executives, and departmental funders to explore how their work responded to the social determinants of health and the dilemmas in doing so. The six case study sites included an Aboriginal Community Controlled Organisation, a sexual health non-government organisation, and four services funded and managed by the South Australian government. Results While respondents varied in the extent to which they exhibited an understanding of social determinants most were reflexive about the constraints on their ability to take action. Services’ responses to social determinants included delivering services in a way that takes account of the limitations individuals face from their life circumstances, and physical spaces in the primary health care services being designed to do more than simply deliver services to individuals. The services also undertake advocacy for policies that create healthier communities but note barriers to them doing this work. Our findings suggest that primary health care workers are required to transverse “dilemmatic space” in their work. Conclusions The absence of systematic supportive policy, frameworks and structure means that it is hard for PHC services to act on the Commission on the Social Determinants of Health’s recommendations. Our study does, however, provide evidence of the potential for PHC services to be more responsive to social determinants given more support and by building alliances with communities and

  18. 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

  19. Cardiovascular Actions and Therapeutic Potential of Tetramethylpyrazine (Active Component Isolated from Rhizoma Chuanxiong): Roles and Mechanisms

    PubMed Central

    Guo, Ming; Liu, Yue; Shi, Dazhuo

    2016-01-01

    Tetramethylpyrazine (TMP), a pharmacologically active component isolated from the rhizome of the Chinese herb Rhizoma Chuanxiong (Chuanxiong), has been clinically used in China and Southeast Asian countries for the prevention and treatment of cardiovascular diseases (CVDs) for about fifty years. The pharmacological effects of TMP on the cardiovascular system have attracted great interest. Emerging experimental studies and clinical trials have demonstrated that TMP prevents atherosclerosis as well as ischemia-reperfusion injury. The cardioprotective effects of TMP are mainly related to its antioxidant, anti-inflammatory, or calcium-homeostasis effects. This review focuses on the roles and mechanisms of action of TMP in the cardiovascular system and provides a novel perspective on TMP's clinical use. PMID:27314011

  20. Cardiovascular Actions and Therapeutic Potential of Tetramethylpyrazine (Active Component Isolated from Rhizoma Chuanxiong): Roles and Mechanisms.

    PubMed

    Guo, Ming; Liu, Yue; Shi, Dazhuo

    2016-01-01

    Tetramethylpyrazine (TMP), a pharmacologically active component isolated from the rhizome of the Chinese herb Rhizoma Chuanxiong (Chuanxiong), has been clinically used in China and Southeast Asian countries for the prevention and treatment of cardiovascular diseases (CVDs) for about fifty years. The pharmacological effects of TMP on the cardiovascular system have attracted great interest. Emerging experimental studies and clinical trials have demonstrated that TMP prevents atherosclerosis as well as ischemia-reperfusion injury. The cardioprotective effects of TMP are mainly related to its antioxidant, anti-inflammatory, or calcium-homeostasis effects. This review focuses on the roles and mechanisms of action of TMP in the cardiovascular system and provides a novel perspective on TMP's clinical use. PMID:27314011

  1. Larval therapy from antiquity to the present day: mechanisms of action, clinical applications and future potential

    PubMed Central

    Whitaker, Iain S; Twine, Christopher; Whitaker, Michael J; Welck, Mathew; Brown, Charles S; Shandall, Ahmed

    2007-01-01

    When modern medicine fails, it is often useful to draw ideas from ancient treatments. The therapeutic use of fly larvae to debride necrotic tissue, also known as larval therapy, maggot debridement therapy or biosurgery, dates back to the beginnings of civilisation. Despite repeatedly falling out of favour largely because of patient intolerance to the treatment, the practice of larval therapy is increasing around the world because of its efficacy, safety and simplicity. Clinical indications for larval treatment are varied, but, in particular, are wounds infected with multidrug‐resistant bacteria and the presence of significant co‐morbidities precluding surgical intervention. The flies most often used in larval therapy are the facultative calliphorids, with the greenbottle blowfly (Lucilia sericata) being the most widely used species. This review summarises the fascinating and turbulent history of larval therapy from its origin to the present day, including mechanisms of action and evidence for its clinical applications. It also explores future research directions. PMID:17551073

  2. Assessing potential targets of calcium action in light-modulated gravitropism

    NASA Technical Reports Server (NTRS)

    Roux, S. J.

    1995-01-01

    Light, through the mediation of the pigment phytochrome, modulates the gravitropic response of the shoots and roots of many plants. The transduction of both light and gravity stimuli appears to involve Ca(2+)-regulated steps, one or more of which may represent points of intersection between the two transduction chains. To be confident that Ca2+ plays a critical role in stimulus-response coupling for gravitropism, it will be important to identify specific targets of Ca2+ action whose function can be clearly linked to the regulation of growth. Calcium typically exerts its influence on cell metabolism through binding to and activating key regulatory proteins. The three best characterized of these proteins in plants are the calmodulins, calcium-dependent protein kinases, and annexins. In this review we summarize what is known about the structure and function of these proteins and speculate on how their activation by Ca2+ could influence the differential growth response of gravitropism.

  3. HMGB1 Inhibition During Zymosan-Induced Inflammation: The Potential Therapeutic Action of Riboflavin.

    PubMed

    Mazur-Bialy, Agnieszka Irena; Pocheć, Ewa

    2016-04-01

    Sepsis, also known as systemic inflammatory response syndrome, is a life-threatening condition caused by a pathogenic agent and leading to multiple organ dysfunction syndrome. One of the factors responsible for the excessive intensification of the inflammatory response in the course of inflammation is high-mobility group protein B1 (HMGB1). HMG-1 is a nuclear protein which, after being released to the intercellular space, has a highly pro-inflammatory effect and acts as a late mediator of lethal damage. The purpose of this study was to examine whether the anti-inflammatory action of riboflavin is accompanied by inhibition of HMGB1 release during peritoneal inflammation and zymosan stimulation of macrophages. Peritonitis was induced in male BALB/c and C57BL/6J mice via intraperitoneal injection of zymosan (40 mg/kg). RAW 264.7 macrophages were activated with zymosan (250 µg/ml). Riboflavin (mice, 50 mg/kg; RAW 264.7, 25 µg/ml) was administered 30 min before zymosan, simultaneously with, or 2, 4, 6 h after zymosan. Additionally, mRNA expression of HMGB1 and its intracellular and serum levels were evaluated. The research showed that riboflavin significantly reduces both the expression and the release of HMGB1; however, the effect of riboflavin was time-dependent. The greatest efficacy was found when riboflavin was given 30 min prior to zymosan, and also 2 and 4 h (C57BL/6J; RAW 264.7) or 4 and 6 h (BALB/c) after zymosan. Research showed that riboflavin influences the level of HMGB1 released in the course of inflammation; however, further study is necessary to determine its mechanisms of action. PMID:26445809

  4. Mosquito larvicidal and pupaecidal potential of prodigiosin from Serratia marcescens and understanding its mechanism of action.

    PubMed

    Suryawanshi, Rahul K; Patil, Chandrashekhar D; Borase, Hemant P; Narkhede, Chandrakant P; Salunke, Bipinchandra K; Patil, Satish V

    2015-09-01

    Mosquitoes spread lethal diseases like malaria and dengue fever to humans. Considering mosquito vector control as one of the best alternatives to reduce new infections, here we have analyzed the effect of purified pigment prodigiosin extracted from Serratia marcescens (NMCC 75) against larval and pupal stages of Aedes aegypti and Anopheles stephensi mosquitoes. Mosquito larvicidal activities of purified prodigiosin revealed LC50 values of 14 ± 1.2, 15.6 ± 1.48, 18 ± 1.3, 21 ± 0.87 µg/ml against early IInd, IIIrd, IVth instar and pupal stages of Ae. aegypti, respectively. LC50 values for An. stephensi were found to be 19.7 ± 1.12, 24.7 ± 1.47, 26.6 ± 1.67, 32.2 ± 1.79 µg/ml against early IInd, IIIrd, IVth instar and pupae of An. stephensi, respectively. Further investigations toward understanding modes of action revealed variations in the activities of esterases, acetylcholine esterases, phosphatases, proteases and total proteins in the fourth instar larvae of Ae. aegypti indicating intrinsic difference in biochemical features due to prodigiosin treatment. Although there was no inhibition of enzymes like catalase and oxidase but may have profound inhibitory effect on carbonic anhydrase or H(+)-V-ATPase which is indicated by change in the pH of midgut and caeca of mosquito larvae. This reduced pH may be possibly due to the proton pump inhibitory activity of prodigiosin. Pure prodigiosin can prove to be an important molecule for mosquito control at larval and pupal stages of Ae. aegypti and An. stephensi. This is the first report on the mosquito pupaecidal activity of prodigiosin and its possible mechanism of action.

  5. Prostate resection - minimally invasive - discharge

    MedlinePlus

    Laser prostatectomy - discharge; Transurethral needle ablation - discharge; TUNA - discharge; Transurethral incision - discharge; TUIP - discharge; Holmium laser enucleation of the prostate - discharge; HoLep - discharge; Interstitial laser ...

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

    PubMed

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

    1995-10-01

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

  7. [Nipple discharge].

    PubMed

    Deodato, G; Consoli, A; Riggi, M; Longo, G; Finocchiaro, G B

    1981-02-01

    The Authors examine the various types of breast discharge concentrating in particular on the secretions due to inherent pathology. After having studied origin, they concentrate on the diagnostic significance and the limits of exfoliative cytology and contrast mammography. The Authors conclude by presenting an original protocol of treatment of the afflicted breast illustrating in addition, the various surgical techniques proposed for the cure of the sicknesses of intramammary origin that cause abnormal discharge. PMID:7261200

  8. Mechanisms of CaMKII action in long-term potentiation

    PubMed Central

    Lisman, John; Yasuda, Ryohei; Raghavachari, Sridhar

    2014-01-01

    Long-term potentiation (LTP) of synaptic strength occurs during learning and can last for long periods, making it a probable mechanism for memory storage. LTP induction results in calcium entry, which activates calcium–calmodulin-dependent protein kinase II (CaMKII). CaMKII subsequently translocates to the synapse, where it binds to the NMDA-type glutamate receptors and produces potentiation by phosphorylating principal and auxiliary subunits of AMPA-type glutamate receptors. These processes all are localized to stimulated spines and account for the synapse specificity of LTP. In the later stages of LTP, CaMKII has a structural role in enlarging and strengthening the synapse. PMID:22334212

  9. A clinically applicable approach for detecting spontaneous action potential spikes in amyotrophic lateral sclerosis with a linear electrode array.

    PubMed

    Jahanmiri-Nezhad, Faezeh; Li, Xiaoyan; Barkhaus, Paul E; Rymer, William Z; Zhou, Ping

    2014-02-01

    Examination of spontaneous muscle activity is an important part of the routine electromyogram (EMG) in assessing neuromuscular diseases. The EMG is specifically valuable as a diagnostic test in supporting the diagnosis of amyotrophic lateral sclerosis. High-density surface EMG is a relatively new technique that has until now been used in research but has the potential for clinical application. This study presents a simple high-density surface EMG method for automatic detection of spontaneous action potentials from surface electrode array recordings of patients with amyotrophic lateral sclerosis. To reduce computational complexity while maintaining useful information from the electrode array recording, the multichannel high-density surface EMG was transferred to single-dimensional data by calculating the maximum difference across all channels of the electrode array. A spike detection threshold was then set in the single-dimensional domain to identify the firing times of each spontaneous action potential spike, whereas a spike extraction threshold was used to define the onset and offset of the spontaneous spikes. These data were used to extract the spontaneous spike waveforms from the electrode array EMG. A database of detected spontaneous spikes was thus obtained, including their waveforms, on all channels along with their corresponding firing times. This newly developed method makes use of the information from different channels of the electrode array EMG recording. It also has the primary feature of being simple and fast in implementation, with convenient parameter adjustment and user-computer interaction. Hence, it has good possibilities for clinical application.

  10. The spatio-temporal characteristics of action potential initiation in layer 5 pyramidal neurons: a voltage imaging study

    PubMed Central

    Popovic, Marko A; Foust, Amanda J; McCormick, David A; Zecevic, Dejan

    2011-01-01

    Abstract The spatial pattern of Na+ channel clustering in the axon initial segment (AIS) plays a critical role in tuning neuronal computations, and changes in Na+ channel distribution have been shown to mediate novel forms of neuronal plasticity in the axon. However, immunocytochemical data on channel distribution may not directly predict spatio-temporal characteristics of action potential initiation, and prior electrophysiological measures are either indirect (extracellular) or lack sufficient spatial resolution (intracellular) to directly characterize the spike trigger zone (TZ). We took advantage of a critical methodological improvement in the high sensitivity membrane potential imaging (Vm imaging) technique to directly determine the location and length of the spike TZ as defined in functional terms. The results show that in mature axons of mouse cortical layer 5 pyramidal cells, action potentials initiate in a region ∼20 μm in length centred between 20 and 40 μm from the soma. From this region, the AP depolarizing wave invades initial nodes of Ranvier within a fraction of a millisecond and propagates in a saltatory fashion into axonal collaterals without failure at all physiologically relevant frequencies. We further demonstrate that, in contrast to the saltatory conduction in mature axons, AP propagation is non-saltatory (monotonic) in immature axons prior to myelination. PMID:21669974

  11. Novel experimental results in human cardiac electrophysiology: measurement of the Purkinje fibre action potential from the undiseased human heart.

    PubMed

    Nagy, Norbert; Szél, Tamás; Jost, Norbert; Tóth, András; Gy Papp, Julius; Varró, András

    2015-09-01

    Data obtained from canine cardiac electrophysiology studies are often extrapolated to the human heart. However, it has been previously demonstrated that because of the lower density of its K(+) currents, the human ventricular action potential has a less extensive repolarization reserve. Since the relevance of canine data to the human heart has not yet been fully clarified, the aim of the present study was to determine for the first time the action potentials of undiseased human Purkinje fibres (PFs) and to compare them directly with those of dog PFs. All measurements were performed at 37 °C using the conventional microelectrode technique. At a stimulation rate of 1 Hz, the plateau potential of human PFs is more positive (8.0 ± 1.8 vs 8.6 ± 3.4 mV, n = 7), while the amplitude of the spike is less pronounced. The maximal rate of depolarization is significantly lower in human PKs than in canine PFs (406.7 ± 62 vs 643 ± 36 V/s, respectively, n = 7). We assume that the appreciable difference in the protein expression profiles of the 2 species may underlie these important disparities. Therefore, caution is advised when canine PF data are extrapolated to humans, and further experiments are required to investigate the characteristics of human PF repolarization and its possible role in arrhythmogenesis.

  12. Exercise-induced expression of cardiac ATP-sensitive potassium channels promotes action potential shortening and energy conservation.

    PubMed

    Zingman, Leonid V; Zhu, Zhiyong; Sierra, Ana; Stepniak, Elizabeth; Burnett, Colin M-L; Maksymov, Gennadiy; Anderson, Mark E; Coetzee, William A; Hodgson-Zingman, Denice M

    2011-07-01

    Physical activity is one of the most important determinants of cardiac function. The ability of the heart to increase delivery of oxygen and metabolic fuels relies on an array of adaptive responses necessary to match bodily demand while avoiding exhaustion of cardiac resources. The ATP-sensitive potassium (K(ATP)) channel has the unique ability to adjust cardiac membrane excitability in accordance with ATP and ADP levels, and up-regulation of its expression that occurs in response to exercise could represent a critical element of this adaption. However, the mechanism by which K(ATP) channel expression changes result in a beneficial effect on cardiac excitability and function remains to be established. Here, we demonstrate that an exercise-induced rise in K(ATP) channel expression enhanced the rate and magnitude of action potential shortening in response to heart rate acceleration. This adaptation in membrane excitability promoted significant reduction in cardiac energy consumption under escalating workloads. Genetic disruption of normal K(ATP) channel pore function abolished the exercise-related changes in action potential duration adjustment and caused increased cardiac energy consumption. Thus, an expression-driven enhancement in the K(ATP) channel-dependent membrane response to alterations in cardiac workload represents a previously unrecognized mechanism for adaptation to physical activity and a potential target for cardioprotection.

  13. Visual Stimuli Evoked Action Potentials Trigger Rapidly Propagating Dendritic Calcium Transients in the Frog Optic Tectum Layer 6 Neurons

    PubMed Central

    Svirskis, Gytis; Baranauskas, Gytis; Svirskiene, Natasa; Tkatch, Tatiana

    2015-01-01

    The superior colliculus in mammals or the optic tectum in amphibians is a major visual information processing center responsible for generation of orientating responses such as saccades in monkeys or prey catching avoidance behavior in frogs. The conserved structure function of the superior colliculus the optic tectum across distant species such as frogs, birds monkeys permits to draw rather general conclusions after studying a single species. We chose the frog optic tectum because we are able to perform whole-cell voltage-clamp recordings fluorescence imaging of tectal neurons while they respond to a visual stimulus. In the optic tectum of amphibians most visual information is processed by pear-shaped neurons possessing long dendritic branches, which receive the majority of synapses originating from the retinal ganglion cells. Since the first step of the retinal input integration is performed on these dendrites, it is important to know whether this integration is enhanced by active dendritic properties. We demonstrate that rapid calcium transients coinciding with the visual stimulus evoked action potentials in the somatic recordings can be readily detected up to the fine branches of these dendrites. These transients were blocked by calcium channel blockers nifedipine CdCl2 indicating that calcium entered dendrites via voltage-activated L-type calcium channels. The high speed of calcium transient propagation, >300 μm in <10 ms, is consistent with the notion that action potentials, actively propagating along dendrites, open voltage-gated L-type calcium channels causing rapid calcium concentration transients in the dendrites. We conclude that such activation by somatic action potentials of the dendritic voltage gated calcium channels in the close vicinity to the synapses formed by axons of the retinal ganglion cells may facilitate visual information processing in the principal neurons of the frog optic tectum. PMID:26414356

  14. Loss of Local Astrocyte Support Disrupts Action Potential Propagation and Glutamate Release Synchrony from Unmyelinated Hippocampal Axon Terminals In Vitro

    PubMed Central

    Sobieski, Courtney; Jiang, Xiaoping; Crawford, Devon C.

    2015-01-01

    Neuron–astrocyte interactions are critical for proper CNS development and function. Astrocytes secrete factors that are pivotal for synaptic development and function, neuronal metabolism, and neuronal survival. Our understanding of this relationship, however, remains incomplete due to technical hurdles that have prevented the removal of astrocytes from neuronal circuits without changing other important conditions. Here we overcame this obstacle by growing solitary rat hippocampal neurons on microcultures that were comprised of either an astrocyte bed (+astrocyte) or a collagen bed (−astrocyte) within the same culture dish. −Astrocyte autaptic evoked EPSCs, but not IPSCs, displayed an altered temporal profile, which included increased synaptic delay, increased time to peak, and severe glutamate release asynchrony, distinct from previously described quantal asynchrony. Although we observed minimal alteration of the somatically recorded action potential waveform, action potential propagation was altered. We observed a longer latency between somatic initiation and arrival at distal locations, which likely explains asynchronous EPSC peaks, and we observed broadening of the axonal spike, which likely underlies changes to evoked EPSC onset. No apparent changes in axon structure were observed, suggesting altered axonal excitability. In conclusion, we propose that local astrocyte support has an unappreciated role in maintaining glutamate release synchrony by disturbing axonal signal propagation. SIGNIFICANCE STATEMENT Certain glial cell types (oligodendrocytes, Schwann cells) facilitate the propagation of neuronal electrical signals, but a role for astrocytes has not been identified despite many other functions of astrocytes in supporting and modulating neuronal signaling. Under identical global conditions, we cultured neurons with or without local astrocyte support. Without local astrocytes, glutamate transmission was desynchronized by an alteration of the waveform

  15. The influence of Savannah River discharge and changing SRS cooling water requirements on the potential entrainment of ichthyoplankton at the SRS Savannah River intakes

    SciTech Connect

    Paller, M.H.

    1992-08-01

    Entrainment (i.e., withdrawal of fish larvae and eggs in cooling water) at the SRS Savannah River intakes is greatest when periods of high river water usage coincide with low river dischargeduring the spawning season. American shad and striped bass are the two species of greatest concern because of their recreational and/or commercial importance and because they produce drifting eggs and larvae vulnerable to entrainment. In the mid-reaches of the Savannah River, American shad and striped bass spawn primarily during April and May. An analysis of Savannah River discharge during April and May 1973--1989 indicated the potential for entrainment of 4--18% of the American shad and striped bass larvae and eggs that drifted past the SRS. This analysis assumed the concurrent operation of L-, K-, and P-Reactors. Additional scenarios investigated were: (1) shutting down L- and P-Reactors, and operating K-Reactor with a recycle cooling tower; and (2) shutting down L- and P-Reactors, eliminating minimum flows to Steel Creek, and operating K-Reactor with a recycle cooling tower. The former scenario reduced potential entrainment to 0.7--3.3%, and the latter scenario reduced potential entrainment to 0.20.8%. Thus, the currently favored scenario of operating K-Reactor with a cooling tower and not operating L- and P-Reactors represents a significant lessening of the impact of SRS operations.

  16. Overexpression of the Large-Conductance, Ca2+-Activated K+ (BK) Channel Shortens Action Potential Duration in HL-1 Cardiomyocytes

    PubMed Central

    Stimers, Joseph R.; Song, Li; Rusch, Nancy J.; Rhee, Sung W.

    2015-01-01

    Long QT syndrome is characterized by a prolongation of the interval between the Q wave and the T wave on the electrocardiogram. This abnormality reflects a prolongation of the ventricular action potential caused by a number of genetic mutations or a variety of drugs. Since effective treatments are unavailable, we explored the possibility of using cardiac expression of the large-conductance, Ca2+-activated K+ (BK) channel to shorten action potential duration (APD). We hypothesized that expression of the pore-forming α subunit of human BK channels (hBKα) in HL-1 cells would shorten action potential duration in this mouse atrial cell line. Expression of hBKα had minimal effects on expression levels of other ion channels with the exception of a small but significant reduction in Kv11.1. Patch-clamped hBKα expressing HL-1 cells exhibited an outward voltage- and Ca2+-sensitive K+ current, which was inhibited by the BK channel blocker iberiotoxin (100 nM). This BK current phenotype was not detected in untransfected HL-1 cells or in HL-1 null cells sham-transfected with an empty vector. Importantly, APD in hBKα-expressing HL-1 cells averaged 14.3 ± 2.8 ms (n = 10), which represented a 53% reduction in APD compared to HL-1 null cells lacking BKα expression. APD in the latter cells averaged 31.0 ± 5.1 ms (n = 13). The shortened APD in hBKα-expressing cells was restored to normal duration by 100 nM iberiotoxin, suggesting that a repolarizing K+ current attributed to BK channels accounted for action potential shortening. These findings provide initial proof-of-concept that the introduction of hBKα channels into a cardiac cell line can shorten APD, and raise the possibility that gene-based interventions to increase hBKα channels in cardiac cells may hold promise as a therapeutic strategy for long QT syndrome. PMID:26091273

  17. Heart attack - discharge

    MedlinePlus

    Myocardial infarction - discharge; MI - discharge; Coronary event - discharge; Infarct - discharge ... patients with unstable angina/non-ST-Elevation myocardial infarction: a report of the American College of Cardiology/ ...

  18. Compilation of data to estimate groundwater migration potential for constituents in active liquid discharges at the Hanford Site

    SciTech Connect

    Ames, L.L.; Serne, R.J.

    1991-03-01

    A preliminary characterization of the constituents present in the 33 liquid waste streams at the US Department of Energy's Hanford Site has been completed by Westinghouse Hanford Company. In addition, Westinghouse Hanford has summarized the soil characteristics based on drill logs collected at each site that receives these liquid wastes. Literature searches were conducted and available Hanford-specific data were tabulated and reviewed. General literature on organic chemicals present in the liquid waste streams was also reviewed. Using all of this information, Pacific Northwest Laboratory has developed a best estimate of the transport characteristics (water solubility and soil adsorption properties) for those radionuclides and inorganic and organic chemicals identified in the various waste streams. We assume that the potential for transport is qualified through the four geochemical parameters: solubility, distribution coefficient, persistence (radiogenic or biochemical half-life), and volatility. Summary tables of these parameters are presented for more than 50 inorganic and radioactive species and more than 50 organic compounds identified in the liquid waste streams. Brief descriptions of the chemical characteristics of Hanford sediments, solubility, and adsorption processes, and of how geochemical parameters are used to estimate migration in groundwater-sediment environments are also presented. Groundwater monitoring data are tabulated for wells neighboring the facilities that receive the liquid wastes. 91 refs., 16 figs., 23 tabs.

  19. Lactate Transport and Receptor Actions in Retina: Potential Roles in Retinal Function and Disease.

    PubMed

    Kolko, Miriam; Vosborg, Fia; Henriksen, Ulrik L; Hasan-Olive, Md Mahdi; Diget, Elisabeth Holm; Vohra, Rupali; Gurubaran, Iswariya Raja Sridevi; Gjedde, Albert; Mariga, Shelton Tendai; Skytt, Dorte M; Utheim, Tor Paaske; Storm-Mathisen, Jon; Bergersen, Linda H

    2016-06-01

    In retina, like in brain, lactate equilibrates across cell membranes via monocarboxylate transporters and in the extracellular space by diffusion, forming a basis for the action of lactate as a transmitter of metabolic signals. In the present paper, we argue that the lactate receptor GPR81, also known as HCAR1, may contribute importantly to the control of retinal cell functions in health and disease. GPR81, a G-protein coupled receptor, is known to downregulate cAMP both in adipose and nervous tissue. The receptor also acts through other down-stream mechanisms to control functions, such as excitability, metabolism and inflammation. Recent publications predict effects of the lactate receptor on neurodegeneration. Neurodegenerative diseases in retina, where the retinal ganglion cells die, notably glaucoma and diabetic retinopathy, may be linked to disturbed lactate homeostasis. Pilot studies reveal high GPR81 mRNA in retina and indicate GPR81 localization in Müller cells and retinal ganglion cells. Moreover, monocarboxylate transporters are expressed in retinal cells. We envision that lactate receptors and transporters could be useful future targets of novel therapeutic strategies to protect neurons and prevent or counteract glaucoma as well as other retinal diseases. PMID:26677077

  20. Immunomodulatory effects of fluoxetine: A new potential pharmacological action for a classic antidepressant drug?

    PubMed

    Di Rosso, María Emilia; Palumbo, María Laura; Genaro, Ana María

    2016-07-01

    Selective serotonin reuptake inhibitors are frequently used antidepressants. In particular, fluoxetine is usually chosen for the treatment of the symptoms of depression, obsessive-compulsive, panic attack and bulimia nervosa. Antidepressant therapy has been associated with immune dysfunction. However, there is contradictory evidence about the effect of fluoxetine on the immune system. Experimental findings indicate that lymphocytes express the serotonin transporter. Moreover it has been shown that fluoxetine is able to modulate the immune function through a serotonin-dependent pathway and through a novel independent mechanism. In addition, several studies have shown that fluoxetine can alter tumor cell viability. Thus, it was recently demonstrated in vivo that chronic fluoxetine treatment inhibits tumor growth by increasing antitumor T-cell activity. Here we briefly review some of the literature referring to how fluoxetine is able to modify, for better or worse, the functionality of the immune system. These results of our analysis point to the relevance of the novel pharmacological action of this drug as an immunomodulator helping to treat several pathologies in which immune deficiency and/or deregulation is present.

  1. Opioid antagonist naloxone potentiates anxiogenic-like action of cholecystokinin agonists in elevated plus-maze.

    PubMed

    Kõks, S; Soosaar, A; Võikar, V; Volke, V; Ustav, M; Männistö, P T; Bourin, M; Vasar, E

    1998-06-01

    This study investigated the interplay of cholecystokinin (CCK) and endogenous opioid peptides in the regulation of anxiety. The acute administration of non-selective CCK agonist caerulein (1 and 5 microg/kg) and a selective CCK(B) receptor agonist BOC-CCK-4 (1, 10 and 50 microg/kg) induced a dose-dependent anxiogenic-like action in the plus-maze model of anxiety. BOC-CCK-4 displayed a similar efficacy with caerulein, indicating that the described effect was mediated via CCK(B) receptor subtype. The opioid antagonist naloxone itself (0.5 mg/kg) did not change the exploratory activity of rats in the plus-maze. However, the combination of naloxone with the sub-effective doses of caerulein (1 microg/kg) and BOC-CCK-4 (1 microg/kg) induced a significant inhibition of exploratory behaviour in rats. Accordingly, CCK and endogenous opioid peptides have an antagonistic role in the exploratory model of anxiety in rats.

  2. Lactate Transport and Receptor Actions in Retina: Potential Roles in Retinal Function and Disease.

    PubMed

    Kolko, Miriam; Vosborg, Fia; Henriksen, Ulrik L; Hasan-Olive, Md Mahdi; Diget, Elisabeth Holm; Vohra, Rupali; Gurubaran, Iswariya Raja Sridevi; Gjedde, Albert; Mariga, Shelton Tendai; Skytt, Dorte M; Utheim, Tor Paaske; Storm-Mathisen, Jon; Bergersen, Linda H

    2016-06-01

    In retina, like in brain, lactate equilibrates across cell membranes via monocarboxylate transporters and in the extracellular space by diffusion, forming a basis for the action of lactate as a transmitter of metabolic signals. In the present paper, we argue that the lactate receptor GPR81, also known as HCAR1, may contribute importantly to the control of retinal cell functions in health and disease. GPR81, a G-protein coupled receptor, is known to downregulate cAMP both in adipose and nervous tissue. The receptor also acts through other down-stream mechanisms to control functions, such as excitability, metabolism and inflammation. Recent publications predict effects of the lactate receptor on neurodegeneration. Neurodegenerative diseases in retina, where the retinal ganglion cells die, notably glaucoma and diabetic retinopathy, may be linked to disturbed lactate homeostasis. Pilot studies reveal high GPR81 mRNA in retina and indicate GPR81 localization in Müller cells and retinal ganglion cells. Moreover, monocarboxylate transporters are expressed in retinal cells. We envision that lactate receptors and transporters could be useful future targets of novel therapeutic strategies to protect neurons and prevent or counteract glaucoma as well as other retinal diseases.

  3. Immunomodulatory effects of fluoxetine: A new potential pharmacological action for a classic antidepressant drug?

    PubMed

    Di Rosso, María Emilia; Palumbo, María Laura; Genaro, Ana María

    2016-07-01

    Selective serotonin reuptake inhibitors are frequently used antidepressants. In particular, fluoxetine is usually chosen for the treatment of the symptoms of depression, obsessive-compulsive, panic attack and bulimia nervosa. Antidepressant therapy has been associated with immune dysfunction. However, there is contradictory evidence about the effect of fluoxetine on the immune system. Experimental findings indicate that lymphocytes express the serotonin transporter. Moreover it has been shown that fluoxetine is able to modulate the immune function through a serotonin-dependent pathway and through a novel independent mechanism. In addition, several studies have shown that fluoxetine can alter tumor cell viability. Thus, it was recently demonstrated in vivo that chronic fluoxetine treatment inhibits tumor growth by increasing antitumor T-cell activity. Here we briefly review some of the literature referring to how fluoxetine is able to modify, for better or worse, the functionality of the immune system. These results of our analysis point to the relevance of the novel pharmacological action of this drug as an immunomodulator helping to treat several pathologies in which immune deficiency and/or deregulation is present. PMID:26644208

  4. Ameliorating treatment-refractory depression with intranasal ketamine: potential NMDA receptor actions in the pain circuitry representing mental anguish.

    PubMed

    Opler, Lewis A; Opler, Mark G A; Arnsten, Amy F T

    2016-02-01

    This article reviews the antidepressant actions of ketamine, an N-methyl-D-aspartame glutamate receptor (NMDAR) antagonist, and offers a potential neural mechanism for intranasal ketamine's ultra-rapid actions based on the key role of NMDAR in the nonhuman primate prefrontal cortex (PFC). Although intravenous ketamine infusions can lift mood within hours, the current review describes how intranasal ketamine administration can have ultra-rapid antidepressant effects, beginning within minutes (5-40 minutes) and lasting hours, but with repeated treatments needed for sustained antidepressant actions. Research in rodents suggests that increased synaptogenesis in PFC may contribute to the prolonged benefit of ketamine administration, beginning hours after administration. However, these data cannot explain the relief that occurs within minutes of intranasal ketamine delivery. We hypothesize that the ultra-rapid effects of intranasal administration in humans may be due to ketamine blocking the NMDAR circuits that generate the emotional representations of pain (eg, Brodmann Areas 24 and 25, insular cortex), cortical areas that can be overactive in depression and which sit above the nasal epithelium. In contrast, NMDAR blockade in the dorsolateral PFC following systemic administration of ketamine may contribute to cognitive deficits. This novel view may help to explain how intravenous ketamine can treat the symptoms of depression yet worsen the symptoms of schizophrenia. PMID:25619798

  5. Ameliorating treatment-refractory depression with intranasal ketamine: potential NMDA receptor actions in the pain circuitry representing mental anguish.

    PubMed

    Opler, Lewis A; Opler, Mark G A; Arnsten, Amy F T

    2016-02-01

    This article reviews the antidepressant actions of ketamine, an N-methyl-D-aspartame glutamate receptor (NMDAR) antagonist, and offers a potential neural mechanism for intranasal ketamine's ultra-rapid actions based on the key role of NMDAR in the nonhuman primate prefrontal cortex (PFC). Although intravenous ketamine infusions can lift mood within hours, the current review describes how intranasal ketamine administration can have ultra-rapid antidepressant effects, beginning within minutes (5-40 minutes) and lasting hours, but with repeated treatments needed for sustained antidepressant actions. Research in rodents suggests that increased synaptogenesis in PFC may contribute to the prolonged benefit of ketamine administration, beginning hours after administration. However, these data cannot explain the relief that occurs within minutes of intranasal ketamine delivery. We hypothesize that the ultra-rapid effects of intranasal administration in humans may be due to ketamine blocking the NMDAR circuits that generate the emotional representations of pain (eg, Brodmann Areas 24 and 25, insular cortex), cortical areas that can be overactive in depression and which sit above the nasal epithelium. In contrast, NMDAR blockade in the dorsolateral PFC following systemic administration of ketamine may contribute to cognitive deficits. This novel view may help to explain how intravenous ketamine can treat the symptoms of depression yet worsen the symptoms of schizophrenia.

  6. Potentiation of acetylcholine action by huperzine-A and physostigmine on some vertebrate effectors, including human iris sphincter muscle.

    PubMed

    Patil, Kaustubha D; Buerki, Robin A; Patil, Popat N

    2003-04-01

    The main objective of this investigation was to compare the acetylcholine potentiating action of huperzine-A with acetylcholinesterase inhibitor physostigmine on the frog rectus abdominus muscle, rat phrenic nerve diaphragm preparation, guinea pig ileum and human iris sphincter muscle. In vitro on the frog rectus abdominus muscle, microM of each alkaloid, incubated for 10 min, shifted the acetylcholine concentration response curve to the left. At EC(50) level, physostigmine potentiated acetylcholine response by 4-fold. The potentiation by huperzine-A was 40-fold. The acetylcholine maximum effect, relative to the control, increased to approximately 130% by each alkaloid. Neurally mediated twitch contraction of the rat diaphragm, a skeletal muscle at 1 microM was also potentiated more by huperzine-A than that by physostigmine. Neuromuscular block by (+)-tubocurarine was reversed more easily by huperzine-A than that by physostigmine. On guinea pig ileum, a 30 nM concentration of each alkaloid incubated for 5 min potentiated acetylcholine (10 nM) by 42%, and 33% for huperzine-A and physostigmine respectively. The difference in potentiation between the alkaloids was not significant. At 300 nM of each alkaloid, intrinsic indirect contractions were observed on the ileum, where the rate of contraction by huperzine-A was faster than that by physostigmine. On the iris sphincter, huperzine-A and physostigmine produced a concentration-dependent effect. Maximum effect after each alkaloid was achieved at 30 microM. Potentiation of acetylcholine response by 0.3 microM huperzine-A after a 10-min incubation was greater than that achieved by physostigmine at an equivalent concentration on the contralateral iris sphincter. In summary, huperzine-A exhibits greater acetylcholine potentiating activity on vertebrate muscles than that produced by physostigmine. The results are discussed in relation to the potential therapeutic value of huperzine-A.

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  9. Assessing the variability of glacier lake bathymetries and potential peak discharge based on large-scale measurements in the Cordillera Blanca, Peru

    NASA Astrophysics Data System (ADS)

    Cochachin, Alejo; Huggel, Christian; Salazar, Cesar; Haeberli, Wilfried; Frey, Holger

    2015-04-01

    Over timescales of hundreds to thousands of years ice masses in mountains produced erosion in bedrock and subglacial sediment, including the formation of overdeepenings and large moraine dams that now serve as basins for glacial lakes. Satellite based studies found a total of 8355 glacial lakes in Peru, whereof 830 lakes were observed in the Cordillera Blanca. Some of them have caused major disasters due to glacial lake outburst floods in the past decades. On the other hand, in view of shrinking glaciers, changing water resources, and formation of new lakes, glacial lakes could have a function as water reservoirs in the future. Here we present unprecedented bathymetric studies of 124 glacial lakes in the Cordillera Blanca, Huallanca, Huayhuash and Raura in the regions of Ancash, Huanuco and Lima. Measurements were carried out using a boat equipped with GPS, a total station and an echo sounder to measure the depth of the lakes. Autocad Civil 3D Land and ArcGIS were used to process the data and generate digital topographies of the lake bathymetries, and analyze parameters such as lake area, length and width, and depth and volume. Based on that, we calculated empirical equations for mean depth as related to (1) area, (2) maximum length, and (3) maximum width. We then applied these three equations to all 830 glacial lakes of the Cordillera Blanca to estimate their volumes. Eventually we used three relations from the literature to assess the peak discharge of potential lake outburst floods, based on lake volumes, resulting in 3 x 3 peak discharge estimates. In terms of lake topography and geomorphology results indicate that the maximum depth is located in the center part for bedrock lakes, and in the back part for lakes in moraine material. Best correlations are found for mean depth and maximum width, however, all three empirical relations show a large spread, reflecting the wide range of natural lake bathymetries. Volumes of the 124 lakes with bathymetries amount to 0

  10. Emerging cardiovascular actions of the incretin hormone glucagon-like peptide-1: potential therapeutic benefits beyond glycaemic control?

    PubMed Central

    Grieve, David J; Cassidy, Roslyn S; Green, Brian D

    2009-01-01

    Glucagon-like peptide-1 (GLP-1) is an incretin hormone secreted by the small intestine in response to nutrient ingestion. It has wide-ranging effects on glucose metabolism, including stimulation of insulin release, inhibition of glucagon secretion, reduction of gastric emptying and augmentation of satiety. Importantly, the insulinotropic actions of GLP-1 are uniquely dependent on ambient glucose concentrations, and it is this particular characteristic which has led to its recent emergence as a treatment for type 2 diabetes. Although the major physiological function of GLP-1 appears to be in relation to glycaemic control, there is growing evidence to suggest that it may also play an important role in the cardiovascular system. GLP-1 receptors (GLP-1Rs) are expressed in the heart and vasculature of both rodents and humans, and recent studies have demonstrated that GLP-1R agonists have wide-ranging cardiovascular actions, such as modulation of heart rate, blood pressure, vascular tone and myocardial contractility. Importantly, it appears that these agents may also have beneficial effects in the setting of cardiovascular disease (CVD). For example, GLP-1 has been found to exert cardioprotective actions in experimental models of dilated cardiomyopathy, hypertensive heart failure and myocardial infarction (MI). Preliminary clinical studies also indicate that GLP-1 infusion may improve cardiac contractile function in chronic heart failure patients with and without diabetes, and in MI patients after successful angioplasty. This review will discuss the current understanding of GLP-1 biology, examine its emerging cardiovascular actions in both health and disease and explore the potential use of GLP-1 as a novel treatment for CVD. PMID:19681866

  11. Direct inhibition of arcuate proopiomelanocortin neurons: a potential mechanism for the orexigenic actions of dynorphin

    PubMed Central

    Zhang, Xiaobing; van den Pol, Anthony N

    2013-01-01

    Dynorphin, an endogenous ligand of kappa (κ) opioid receptors, has multiple roles in the brain, and plays a positive role in energy balance and food intake. However, the mechanism for this is unclear. With immunocytochemistry, we find that axonal dynorphin immunoreactivity in the arcuate nucleus is strong, and that a large number of dynorphin-immunoreactive boutons terminate on or near anorexigenic proopiomelanocortin (POMC) cells. Here we provide evidence from whole-cell patch-clamp recording that dynorphin-A (Dyn-A) directly and dose-dependently inhibits arcuate nucleus POMC neurons. Dyn-A inhibition was eliminated by the κ opioid receptor antagonist nor-BNI, but not by the μ receptor antagonist CTAP. The inhibitory effect was mimicked by the κ2 receptor agonist GR89696, but not by the κ1 receptor agonist U69593. No presynaptic effect of κ2 agonists was found. These results suggest that Dyn-A inhibits POMC neurons through activation of the κ2 opioid receptor. In whole-cell voltage clamp, Dyn-A opened G-protein-coupled inwardly rectifying potassium (GIRK)-like channels on POMC neurons. Dynorphin attenuated glutamate and GABA neurotransmission to POMC neurons. In contrast to the strong inhibition of POMC neurons by Dyn-A, we found a weaker direct inhibitory effect of Dyn-A on arcuate nucleus neuropeptide Y (NPY) neurons mediated by both κ1 and κ2 receptors. Taken together, these results indicate a direct inhibitory effect of Dyn-A on POMC neurons through activation of the κ2 opioid receptor and GIRK channels. A number of orexigenic hypothalamic neurons release dynorphin along with other neuropeptides. The inhibition of anorexigenic POMC neurons may be one mechanism underlying the orexigenic actions of dynorphin. PMID:23318874

  12. In vitro antimalarial activity and chloroquine potentiating action of two bisbenzylisoquinoline enantiomer alkaloids isolated from Strychnopsis thouarsii and Spirospermum penduliflorum.

    PubMed

    Ratsimamanga-Urverg, S; Rasoanaivo, P; Ramiaramanana, L; Milijaona, R; Rafatro, H; Verdier, F; Rakoto-Ratsimamanga, A; Le Bras, J

    1992-12-01

    The bisbenzylisoquinolines 7-O-demethyltetrandrine and limacine, respectively, isolated from Strychnopsis thouarsii Baill. and Spirospermum penduliflorum Thou. were evaluated for their intrinsic antimalarial activity in vitro and chloroquine potentiating action against the chloroquine-resistant Plasmodium falciparum FCM 29 originating from Cameroon. They both showed significant antiplasmodial potency in vitro with very similar IC50 values of respectively, 740 nM and 789 nM (IC50 = 214 nM for chloroquine used as standard drug), which demonstrated that the stereochemistry of the C-1 and C-1' configuration likely plays a role in the chloroquine potentiating effect of these drugs. If confirmed in vivo, these results may account for the traditional use of the two plants as antimalarials and adjuvant to chloroquine in Madagascan folklore remedies. PMID:1484894

  13. Action potentials of HL-1 cells recorded with silicon nanowire transistors

    NASA Astrophysics Data System (ADS)

    Eschermann, Jan Felix; Stockmann, Regina; Hueske, Martin; Vu, Xuan Thang; Ingebrandt, Sven; Offenhäusser, Andreas

    2009-08-01

    Silicon nanowire (NW) transistors were fabricated in a top-down process. These devices were used to record the extracellular potential of the spontaneous activity of cardiac muscle HL-1 cells. Their signals were measured by direct dc sampling of the drain current. An improved signal-to-noise ratio compared to planar field-effect devices was observed. Furthermore the signal shape was evaluated and could be associated to different membrane currents. With these experiments, a qualitative description of the properties of the cell-NW contact was obtained and the suitability of these sensors for electrophysiological measurements in vitro was demonstrated.

  14. Effects of changes in frequency on guinea pig ventricular action potential duration and on QT interval under different experimental conditions.

    PubMed

    von Savigny, L; Hohnloser, S; Antoni, H

    1981-01-01

    Isolated perfused guinea pig hearts (Langendorff preparation) were arrested by carbachol (0.1-0.2 mg/l) and electrically stimulated in the region of the av-conducting system. The QT interval was determined by means of extracellular electrodes at different driving frequencies. Separate experiments were performed on papillary muscles from the right ventricle to measure the duration of the transmembrane action potential under comparable conditions. At 35 degrees C (Ke+ 5.4 mmol/l) increasing the frequency of stimulation (range 12-120/min) caused the action potential duration (APD) to decrease to a greater extent than the QT interval. Stepwise rising of the external K+ concentration up to 16.2 mmol/l produced a nearly parallel shift to the APD-frequency relation to lower values. Again, the QT interval was less affected by increasing the external K+ concentration than the APD. Stepwise reduction of the temperature down to 20 degrees C prolonged the APD as well as the QT interval, the effects being more pronounced at lower than at higher stimulation frequencies. Under all examined experimental conditions, the APD proved to be markedly shorter than the QT interval even when the latter is diminished by the duration of QRS. The results suggest that no close relation exists between the APD and the QT interval. The observed divergencies may be due to functional differences among various parts of the ventricles.

  15. 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. .

  16. Endocannabinoids produced upon action potential firing evoke a Cl(-) current via type-2 cannabinoid receptors in the medial prefrontal cortex.

    PubMed

    den Boon, Femke S; Chameau, Pascal; Houthuijs, Kas; Bolijn, Simone; Mastrangelo, Nicolina; Kruse, Chris G; Maccarrone, Mauro; Wadman, Wytse J; Werkman, Taco R

    2014-12-01

    The functional presence of type-2 cannabinoid receptors (CB2Rs) in layer II/III pyramidal neurons of the rat medial prefrontal cortex (mPFC) was recently demonstrated. In the present study, we show that the application of the endocannabinoids (eCBs) 2-arachidonoylglycerol (2-AG) and methanandamide [a stable analog of the eCB anandamide (AEA)] can activate CB2Rs of mPFC layer II/III pyramidal neurons, which subsequently induces a Cl(-) current. In addition, we show that action potential (AP) firing evoked by 20-Hz current injections results in an eCB-mediated opening of Cl(-) channels via CB2R activation. This AP-evoked synthesis of eCBs is dependent on the Ca(2+) influx through N-type voltage-gated calcium channels. Our results indicate that 2-AG is the main eCB involved in this process. Finally, we demonstrate that under physiologically relevant intracellular Cl(-) conditions, 20-Hz AP firing leads to a CB2R-dependent reduction in neuronal excitability. Altogether, our data indicate that eCBs released upon action potential firing can modulate, through CB2R activation, neuronal activity in the mPFC. We discuss how this may be a mechanism to prevent excessive neuronal firing.

  17. Ruby laser-assisted depilation: The mode of action and potential ways of improved outcome

    NASA Astrophysics Data System (ADS)

    Topping, Adam Partington

    Aim - To improve efficacy and lessen side effects resulting from normal mode ruby laser (NMRL)-assisted depilation via a greater understanding of its mode of action and the development of novel methods of reducing associated epidermal damage. Employing a thermal imaging camera and ex vivo hair-bearing skin, the targets for the NMRL (pulse duration 900 musec and spot size 7 mm) were defined, the temperatures reached and the heat dissipation rates determined. Production of heat was confined to the hair follicles, with the peak temperatures reached varying considerably between hairs within the same treatment area and also between individuals. Histological assessment for a known indicator of cellular damage (p53 expression) identified the sites and extent of damage, which correlated with the peak temperatures measured. An energy meter was used to detect the penetration of NMRL light through ex vivo skin, which was found to be deeper than previously theorised. The black-haired mouse (C57B1/10) was assessed both macroscopically and histologically and found to be an acceptable animal model of NMRL depilation and associated epidermal damage. Attempts to reduce the epidermal damage by simply stopping the light reaching the epidermis using a chromophore block were assessed. Chromophore did indeed reduce the amount of epidermal damage detected in laser-irradiated ex vivo human skin, whereas in contrast it increased the wounding seen in the much thinner skin of the mouse. Nevertheless the mouse model showed that this technique did not affect the depilation efficacy. An alternative method of reducing epidermal damage using induction of the cells' intrinsic protective mechanisms (heat shock proteins, HSP) was assessed using cultured keratinocytes and the mouse model. Primarily, the sub-lethal temperature optimum for HSP expression in human keratinocytes was determined, then an in vitro model of NMRL-associated epidermal damage was established and the heat pre-treatment assessed

  18. Stochasticity intrinsic to coupled-clock mechanisms underlies beat-to-beat variability of spontaneous action potential firing in sinoatrial node pacemaker cells.

    PubMed

    Yaniv, Yael; Lyashkov, Alexey E; Sirenko, Syevda; Okamoto, Yosuke; Guiriba, Toni-Rose; Ziman, Bruce D; Morrell, Christopher H; Lakatta, Edward G

    2014-12-01

    Recent evidence indicates that the spontaneous action potential (AP) of isolated sinoatrial node cells (SANCs) is regulated by a system of stochastic mechanisms embodied within two clocks: ryanodine receptors of the "Ca(2+) clock" within the sarcoplasmic reticulum, spontaneously activate during diastole and discharge local Ca(2+) releases (LCRs) beneath the cell surface membrane; clock crosstalk occurs as LCRs activate an inward Na(+)/Ca(2+) exchanger current (INCX), which together with If and decay of K(+) channels prompts the "M clock," the ensemble of sarcolemmal-electrogenic molecules, to generate APs. Prolongation of the average LCR period accompanies prolongation of the average AP beating interval (BI). Moreover, the prolongation of the average AP BI accompanies increased AP BI variability. We hypothesized that both the average AP BI and AP BI variability are dependent upon stochasticity of clock mechanisms reported by the variability of LCR period. We perturbed the coupled-clock system by directly inhibiting the M clock by ivabradine (IVA) or the Ca(2+) clock by cyclopiazonic acid (CPA). When either clock is perturbed by IVA (3, 10 and 30 μM), which has no direct effect on Ca(2+) cycling, or CPA (0.5 and 5 μM), which has no direct effect on the M clock ion channels, the clock system failed to achieve the basal AP BI and both AP BI and AP BI variability increased. The changes in average LCR period and its variability in response to perturbations of the coupled-clock system were correlated with changes in AP beating interval and AP beating interval variability. We conclude that the stochasticity within the coupled-clock system affects and is affected by the AP BI firing rate and rhythm via modulation of the effectiveness of clock coupling. PMID:25257916

  19. Stochasticity intrinsic to coupled-clock mechanisms underlies beat-to-beat variability of spontaneous action potential firing in sinoatrial node pacemaker cells

    PubMed Central

    Yaniv, Yael; Lyashkov, Alexey E.; Sirenko, Syevda; Okamoto, Yosuke; Guiriba, Toni-Rose; Ziman, Bruce D.; Morrell, Christopher H.; Lakatta, Edward G.

    2014-01-01

    Recent evidence indicates that the spontaneous action potential (AP) of isolated sinoatrial node cells (SANC) is regulated by a system of stochastic mechanisms embodied within two clocks: ryanodine receptors of the “Ca2+ clock” within the sarcoplasmic reticulum, spontaneously activate during diastole and discharge local Ca2+ releases (LCRs) beneath the cell surface membrane; clock crosstalk occurs as LCRs activate an inward Na+/Ca2+ exchanger current (INCX), which together with If and decay of K+ channels prompts the “M clock,” the ensemble of sarcolemmal-electrogenic molecules, to generate APs. Prolongation of the average LCR period accompanies prolongation of the average AP beating interval (BI). Moreover, prolongation of the average AP BI accompanies increased AP BI variability. We hypothesized that both the average AP BI and AP BI variability are dependent upon stochasticity of clock mechanisms reported by the variability of LCR period. We perturbed the coupled-clock system by directly inhibiting the M clock by ivabradine (IVA) or the Ca2+ clock by cyclopiazonic acid (CPA). When either clock is perturbed by IVA (3, 10 and 30μM), which has no direct effect on Ca2+ cycling, or CPA ( 0.5 and 5μM), which has no direct effect on the M clock ion channels, the clock system failed to achieve the basal AP BI and both AP BI and AP BI variability increased. The changes in average LCR period and its variability in response to perturbations of the coupled-clock system were correlated with changes in AP beating interval and AP beating interval variability. We conclude that the stochasticity within the coupled-clock system affects and is affected by the AP BI firing rate and rhythm via modulation of the effectiveness of clock coupling. PMID:25257916

  20. Inhibition of protein import into mitochondria by amphiphilic cations: potential targets and mechanism of action.

    PubMed

    Pavlov, P F; Glaser, E

    1998-11-01

    In this paper we describe for the first time the inhibitory effect of three amphiphilic cations, trifluoperazine, propranolol and dibucaine on mitochondrial protein import. The amphiphilic cations did not affect binding of mitochondrial precursor proteins to mitochondria. Import into mitoplasts was affected in a similar manner to intact mitochondria, indicating that the protein import machinery of the inner membrane of mitochondria was responsible for the observed effect. At concentrations which completely inhibited protein import, the amphiphilic cations did not affect the membrane potential (DeltaPsi) across the inner membrane. The inhibitory potency of amphiphilic cations reflects their lipid/water partition coefficient and relatively high concentrations of the drugs were required for complete inhibition, hence we propose that the mechanism of protein import inhibition by amphiphilic cations is due to membrane perturbing effects. We discuss the implications of our findings in view of the possible connection between various inner mitochondrial membrane channels and the protein import pore.

  1. Regulatory T Cells in Autoimmune Diabetes: Mechanisms of Action and Translational Potential.

    PubMed

    Ovcinnikovs, Vitalijs; Walker, Lucy S K

    2015-01-01

    Since the discovery of specialized T cells with regulatory function, harnessing the power of these cells to ameliorate autoimmunity has been a major goal. Here we collate the evidence that regulatory T cells (Treg) can inhibit Type 1 diabetes in animal models and humans. We discuss the anatomical sites and molecular mechanisms of Treg suppressive function in the Type 1 diabetes setting, citing evidence that Treg can function in both the pancreatic lymph nodes and within the pancreatic lesion. Involvement of the CTLA-4 pathway, as well as TGF-β and IL-2 deprivation will be considered. Finally, we summarize current efforts to manipulate Treg therapeutically in individuals with Type 1 diabetes. The translation of this research area from bench to bedside is still in its infancy, but the remarkable therapeutic potential of successfully manipulating Treg populations is clear to see. PMID:26615100

  2. MIF-1 potentiates the action of tricyclic antidepressants in an animal model of depression.

    PubMed

    Kostowski, W; Danysz, W; Dyr, W; Jankowska, E; Krzaścik, P; Pałejko, W; Stefański, R; Płaźnik, A

    1991-01-01

    In the present paper, the effect of simultaneous treatment of rats with low doses of MIF-1 and tricyclic antidepressants on rat behavior in the forced swim test was studied. It was found that MIF-1 stimulated in a dose-dependent manner "active" behavior of animals in this paradigm. The effect of MIF-1 appeared to be independent of changes in rats' locomotion in the open field test. The combined treatment of rats with MIF-1 (0.01 mg/kg IP) and amitriptyline (5 mg/kg IP) or desipramine (1.25 mg/kg) IP) significantly stimulated active behavior in the forced swim test above the level obtained with each of the drugs given separately. The present data suggest the potential clinical efficacy of a combined therapy of depressive patients with MIF-1 and small doses of tricyclic antidepressants.

  3. 'Working' cardiomyocytes exhibiting plateau action potentials from human placenta-derived extraembryonic mesodermal cells.

    PubMed

    Okamoto, Kazuma; Miyoshi, Shunichiro; Toyoda, Masashi; Hida, Naoko; Ikegami, Yukinori; Makino, Hatsune; Nishiyama, Nobuhiro; Tsuji, Hiroko; Cui, Chang-Hao; Segawa, Kaoru; Uyama, Taro; Kami, Daisuke; Miyado, Kenji; Asada, Hironori; Matsumoto, Kenji; Saito, Hirohisa; Yoshimura, Yasunori; Ogawa, Satoshi; Aeba, Ryo; Yozu, Ryohei; Umezawa, Akihiro

    2007-07-15

    The clinical application of cell transplantation for severe heart failure is a promising strategy to improve impaired cardiac function. Recently, an array of cell types, including bone marrow cells, endothelial progenitors, mesenchymal stem cells, resident cardiac stem cells, and embryonic stem cells, have become important candidates for cell sources for cardiac repair. In the present study, we focused on the placenta as a cell source. Cells from the chorionic plate in the fetal portion of the human placenta were obtained after delivery by the primary culture method, and the cells generated in this study had the Y sex chromosome, indicating that the cells were derived from the fetus. The cells potentially expressed 'working' cardiomyocyte-specific genes such as cardiac myosin heavy chain 7beta, atrial myosin light chain, cardiac alpha-actin by gene chip analysis, and Csx/Nkx2.5, GATA4 by RT-PCR, cardiac troponin-I and connexin 43 by immunohistochemistry. These cells were able to differentiate into cardiomyocytes. Cardiac troponin-I and connexin 43 displayed a discontinuous pattern of localization at intercellular contact sites after cardiomyogenic differentiation, suggesting that the chorionic mesoderm contained a large number of cells with cardiomyogenic potential. The cells began spontaneously beating 3 days after co-cultivation with murine fetal cardiomyocytes and the frequency of beating cells reached a maximum on day 10. The contraction of the cardiomyocytes was rhythmical and synchronous, suggesting the presence of electrical communication between the cells. Placenta-derived human fetal cells may be useful for patients who cannot supply bone marrow cells but want to receive stem cell-based cardiac therapy.

  4. Potentiation of the actions of acetylcholine, epibatidine, and nicotine by methyllycaconitine at fetal muscle-type nicotinic acetylcholine receptors.

    PubMed

    Green, Benedict T; Welch, Kevin D; Cook, Daniel; Gardner, Dale R

    2011-07-15

    Methyllycaconitine (MLA) is a norditerpenoid alkaloid found in high abundance in toxic Delphinium (larkspur) species. It is a potent and selective antagonist of α(7)-nicotinic acetylcholine receptors, but has not been well investigated for activity aside from receptor antagonism. The aim of this study was to investigate the effects of MLA alone and in combination with acetylcholine, epibatidine, nicotine, and neostigmine for actions other than receptor antagonism in TE-671 cells expressing (α(1))(2)β(1)γδ nicotinic acetylcholine receptors. Ligand activity was assessed through measurements of membrane potential changes in TE-671 cells using a fluorescent membrane potential-sensitive dye and normalized to the maximum response to epibatidine (10μM). MLA was ineffective in changing cell membrane potential in the absence of other receptor agonists. However at nanomolar concentrations, it acted as a co-agonist to potentiate TE-671 cell responses to acetylcholine, epibatidine, nicotine, and neostigmine. These results suggest that the poisoning of cattle by norditerpenoid alkaloids found in larkspur may be more complex than previously determined.

  5. K+ accumulation and K+ conductance inactivation during action potential trains in giant axons of the squid Sepioteuthis.

    PubMed

    Inoue, I; Tsutsui, I; Brown, E R

    1997-04-15

    1. During action potential trains in giant axons from the squid Sepioteuthis, decline of the peak level of the undershoot potential was observed. The time course of the decline of the undershoot could be fitted with a three-exponential function with time constants of approximately 25, approximately 400 and approximately 7,000 ms, respectively. 2. When the osmolarity of the external solution was doubled by adding glucose (1.2 M), the fast component of undershoot decline, but not the medium and slow components, was significantly reduced. 3. Under voltage clamp in high osmolarity solutions where K+ accumulation was completely removed, repeated depolarizing pulses at 40 Hz (designed to mimic a train of action potentials) elicited K+ currents whose peak value declined. The decline is consistent with inactivation of the K+ conductance (gK). The decline of gK was fitted by a two-exponential function with time constants of approximately 400 and approximately 7,000 ms, respectively. 4. Interventions designed to modify Schwann cell physiology, such as high frequency stimulation (100 Hz, 2 min), externally applied ouabain (100-500 microM), L-glutamate (100 microM), ACh (100 microM), Co2+ (5mM), Ba2+ (2mM), or removal of external Ca2+ by EGTA, had no significant effects on the fast, medium or slow components of undershoot decline. 5. The results suggest that the fast component of undershoot decline represents K+ accumulation in the space between Schwann cell and axolemma. The medium and slow components are the result of axonal gK inactivation. Schwann cells appear to be involved in K+ clearance only to the extent that they provide an efficient physical pathway for the clearance of K+ by extracellular diffusion.

  6. K+ accumulation and K+ conductance inactivation during action potential trains in giant axons of the squid Sepioteuthis.

    PubMed Central

    Inoue, I; Tsutsui, I; Brown, E R

    1997-01-01

    1. During action potential trains in giant axons from the squid Sepioteuthis, decline of the peak level of the undershoot potential was observed. The time course of the decline of the undershoot could be fitted with a three-exponential function with time constants of approximately 25, approximately 400 and approximately 7,000 ms, respectively. 2. When the osmolarity of the external solution was doubled by adding glucose (1.2 M), the fast component of undershoot decline, but not the medium and slow components, was significantly reduced. 3. Under voltage clamp in high osmolarity solutions where K+ accumulation was completely removed, repeated depolarizing pulses at 40 Hz (designed to mimic a train of action potentials) elicited K+ currents whose peak value declined. The decline is consistent with inactivation of the K+ conductance (gK). The decline of gK was fitted by a two-exponential function with time constants of approximately 400 and approximately 7,000 ms, respectively. 4. Interventions designed to modify Schwann cell physiology, such as high frequency stimulation (100 Hz, 2 min), externally applied ouabain (100-500 microM), L-glutamate (100 microM), ACh (100 microM), Co2+ (5mM), Ba2+ (2mM), or removal of external Ca2+ by EGTA, had no significant effects on the fast, medium or slow components of undershoot decline. 5. The results suggest that the fast component of undershoot decline represents K+ accumulation in the space between Schwann cell and axolemma. The medium and slow components are the result of axonal gK inactivation. Schwann cells appear to be involved in K+ clearance only to the extent that they provide an efficient physical pathway for the clearance of K+ by extracellular diffusion. PMID:9147323

  7. Antioxidant action and potential antidiabetic properties of an isoflavonoid-containing soyabean phytochemical extract (SPE).

    PubMed

    Vedavanam, K; Srijayanta, S; O'Reilly, J; Raman, A; Wiseman, H

    1999-11-01

    The potential role of oestrogenic agents, antioxidants and intestinal glucose-uptake inhibitors in the treatment of diabetes is briefly reviewed. Reports in the literature suggest that oestrogen replacement therapy may favourably modulate glucose homeostasis. A soya phytochemical extract (SPE) containing the isoflavone phytoestrogens genistein and daidzein (mostly in their glycone forms as genistin and daidzin) was investigated as an antioxidant and modulator of intestinal glucose-transport. In the present study, SPE was found to protect against glucose-induced oxidation of human low density lipoproteins (LDL) in vitro. Equol (a gut bacterial metabolite of daidzein) was a more effective antioxidant than daidzein or genistein in this system and was of similar antioxidant potency to the dietary flavonols quercetin and kaempferol and to the endogenous antioxidant 17beta-oestradiol. SPE was found to be an inhibitor of glucose uptake into rabbit intestinal brush border membrane vesicles in vitro, though of weaker potency than the classical sodium dependent glucose transporter (SGLT) inhibitor, phlorizin. Thus SPE displays a range of properties which may be of benefit in diabetes, namely as an oestrogenic agent, an inhibitor of intestinal glucose-uptake and a preventive agent for glucose-induced lipid peroxidation. PMID:10548755

  8. Control of Postharvest Bacterial Soft Rot by Gamma Irradiation and its Potential Modes of Action

    PubMed Central

    Jeong, Rae-Dong; Chu, Eun-Hee; Park, Duck Hwan; Park, Hae-Jun

    2016-01-01

    Gamma irradiation was evaluated for its in vitro and in vivo antibacterial activity against a postharvest bacterial pathogen, Erwinia carotovora subsp. carotovora (Ecc). Gamma irradiation in a bacteria cell suspension resulted in a dramatic reduction of the viable counts as well as an increase in the amounts of DNA and protein released from the cells. Gamma irradiation showed complete inactivation of Ecc, especially at a dose of 0.6 kGy. In addition, scanning electron microscopy of irradiated cells revealed severe damage on the surface of most bacterial cells. Along with the morphological changes of cells by gamma irradiation, it also affected the membrane integrity in a dose-dependent manner. The mechanisms by which the gamma irradiation decreased the bacterial soft rot can be directly associated with the disruption of the cell membrane of the bacterial pathogen, along with DNA fragmentation, results in dose-dependent cell inactivation. These findings suggest that gamma irradiation has potential as an antibacterial approach to reduce the severity of the soft rot of paprika. PMID:27147935

  9. Anthocyanins in obesity-associated thrombogenesis: a review of the potential mechanism of action.

    PubMed

    Thompson, Kiara; Pederick, Wayne; Santhakumar, Abishek Bommannan

    2016-05-18

    Platelet dysfunction, oxidative stress and dyslipidemia are important contributors to pro-thrombotic progression particularly in obese and hyper-cholesterolemic populations. Becoming an increasingly widespread endemic, obesity causes a dysfunction in the metabolic system by initiating endothelial dysfunction; increasing free radical production; lipid peroxidation; platelet hyperactivity and aggregation; thereby accelerating thrombogenesis. In the event of increased free radical generation under pro-thrombotic conditions, antioxidants act as scavengers in reducing physiological oxidative stress; free radical-mediated thrombosis and hemostatic function. Anthocyanin, a subclass of the polyphenol family flavonoids has been shown to exhibit anti-dyslipidemic and anti-thrombotic properties by virtue of its antioxidant activity. Current anti-platelet/coagulant therapeutics target specific receptor pathways to relieve the extent of dysfunction and plaque acceleration in pro-thrombotic individuals. Though effective, they have been associated with high bleeding risk and increased response variability. The following review focuses on the potential role of natural dietary anthocyanins in targeting simultaneous mechanistic pathways in alleviating platelet activation, dyslipidemia, and oxidative stress-associated thrombus acceleration in obese pro-thrombotic populations. PMID:27043127

  10. Exploring potential mechanisms of action of natalizumab in secondary progressive multiple sclerosis.

    PubMed

    Sellebjerg, Finn; Cadavid, Diego; Steiner, Deborah; Villar, Luisa Maria; Reynolds, Richard; Mikol, Daniel

    2016-01-01

    Multiple sclerosis (MS) is a common and chronic central nervous system (CNS) demyelinating disease and a leading cause of permanent disability. Patients most often present with a relapsing-remitting disease course, typically progressing over time to a phase of relentless advancement in secondary progressive MS (SPMS), for which approved disease-modifying therapies are limited. In this review, we summarize the pathophysiological mechanisms involved in the development of SPMS and the rationale and clinical potential for natalizumab, which is currently approved for the treatment of relapsing forms of MS, to exert beneficial effects in reducing disease progression unrelated to relapses in SPMS. In both forms of MS, active brain-tissue injury is associated with inflammation; but in SPMS, the inflammatory response occurs at least partly behind the blood-brain barrier and is followed by a cascade of events, including persistent microglial activation that may lead to chronic demyelination and neurodegeneration associated with irreversible disability. In patients with relapsing forms of MS, natalizumab therapy is known to significantly reduce intrathecal inflammatory responses which results in reductions in brain lesions and brain atrophy as well as beneficial effects on clinical measures, such as reduced frequency and severity of relapse and reduced accumulation of disability. Natalizumab treatment also reduces levels of cerebrospinal fluid chemokines and other biomarkers of intrathecal inflammation, axonal damage and demyelination, and has demonstrated the ability to reduce innate immune activation and intrathecal immunoglobulin synthesis in patients with MS. The efficacy of natalizumab therapy in SPMS is currently being investigated in a randomized, double-blind, placebo-controlled trial. PMID:26788129

  11. Microelectrode array recordings of cardiac action potentials as a high throughput method to evaluate pesticide toxicity.

    PubMed

    Natarajan, A; Molnar, P; Sieverdes, K; Jamshidi, A; Hickman, J J

    2006-04-01

    The threat of environmental pollution, biological warfare agent dissemination and new diseases in recent decades has increased research into cell-based biosensors. The creation of this class of sensors could specifically aid the detection of toxic chemicals and their effects in the environment, such as pyrethroid pesticides. Pyrethroids are synthetic pesticides that have been used increasingly over the last decade to replace other pesticides like DDT. In this study we used a high-throughput method to detect pyrethroids by using multielectrode extracellular recordings from cardiac cells. The data from this cell-electrode hybrid system was compared to published results obtained with patch-clamp electrophysiology and also used as an alternative method to further understand pyrethroid effects. Our biosensor consisted of a confluent monolayer of cardiac myocytes cultured on microelectrode arrays (MEA) composed of 60 substrate-integrated electrodes. Spontaneous activity of these beating cells produced extracellular field potentials in the range of 100 microV to nearly 1200 microV with a beating frequency of 0.5-4 Hz. All of the tested pyrethroids; alpha-Cypermethrin, Tetramethrin and Tefluthrin, produced similar changes in the electrophysiological properties of the cardiac myocytes, namely reduced beating frequency and amplitude. The sensitivity of our toxin detection method was comparable to earlier patch-clamp studies, which indicates that, in specific applications, high-throughput extracellular methods can replace single-cell studies. Moreover, the similar effect of all three pyrethroids on the measured parameters suggests, that not only detection of the toxins but, their classification might also be possible with this method. Overall our results support the idea that whole cell biosensors might be viable alternatives when compared to current toxin detection methods. PMID:16198528

  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. Single unit action potentials in humans and the effect of seizure activity

    PubMed Central

    Merricks, Edward M.; Smith, Elliot H.; McKhann, Guy M.; Goodman, Robert R.; Bateman, Lisa M.; Emerson, Ronald G.

    2015-01-01

    Spike-sorting algorithms have been used to identify the firing patterns of isolated neurons (‘single units’) from implanted electrode recordings in patients undergoing assessment for epilepsy surgery, but we do not know their potential for providing helpful clinical information. It is important therefore to characterize both the stability of these recordings and also their context. A critical consideration is where the units are located with respect to the focus of the pathology. Recent analyses of neuronal spiking activity, recorded over extended spatial areas using microelectrode arrays, have demonstrated the importance of considering seizure activity in terms of two distinct spatial territories: the ictal core and penumbral territories. The pathological information in these two areas, however, is likely to be very different. We investigated, therefore, whether units could be followed reliably over prolonged periods of times in these two areas, including during seizure epochs. We isolated unit recordings from several hundred neurons from four patients undergoing video-telemetry monitoring for surgical evaluation of focal neocortical epilepsies. Unit stability could last in excess of 40 h, and across multiple seizures. A key finding was that in the penumbra, spike stereotypy was maintained even during the seizure. There was a net tendency towards increased penumbral firing during the seizure, although only a minority of units (10–20%) showed significant changes over the baseline period, and notably, these also included neurons showing significant reductions in firing. In contrast, within the ictal core territories, regions characterized by intense hypersynchronous multi-unit firing, our spike sorting algorithms failed as the units were incorporated into the seizure activity. No spike sorting was possible from that moment until the end of the seizure, but recovery of the spike shape was rapid following seizure termination: some units reappeared within tens of

  14. Delineating the discharge zone and potential natural attenuation of a chlorinated solvent plume to a gaining lowland river: A multi-scale approach

    NASA Astrophysics Data System (ADS)

    Weatherill, J. J.; Krause, S.; Voyce, K. J.

    2012-04-01

    Chlorinated aliphatic hydrocarbons (CAHs), such as trichloroethene (TCE), are often recalcitrant groundwater pollutants which can form extensive dissolved plumes with the potential to impact on the quality of baseflow to rivers. There is a growing need to evaluate the risk to surface water posed by migrating plumes and the intrinsic potential for natural attenuation along contaminant flow paths through the groundwater/surface water interface (GSI). This study investigates the potential discharge of a poorly defined CAH plume to an accreting section of the River Tern (Shropshire, UK). Groundwater sampling in the area has revealed the presence of TCE (with minor chloroform and carbon tetrachloride) with maximum concentrations discovered at depths of up to 80 m in a number of deep boreholes in an unconfined sandstone aquifer hydraulically connected to the river. We aim to develop a conceptual understanding of spatial patterns of plume discharge at sub-catchment to sediment-scale and assess the potential significance of biogeochemical transformation in the river bed and riparian sediments of a baseflow-dominated lowland river. Concentrations of dissolved CAHs (including the anaerobic metabolites of TCE) were monitored in a reach-scale longitudinal channel network of liquid-liquid passive diffusion samplers, placed in direct contact with the top 10 cm of river bed sediment. Samplers comprised distilled water-filled glass vials capped by a thin (50 μm) film of commercially available LDPE tubing. A long integration time (33 days) was selected for sampler equilibration with in-situ pore water concentrations. Results provided a plan-view reconnaissance survey of TCE distribution in the river bed and indicated tentative core and fringe zones. Spatial connectivity between ground and surface water was mapped by means of an in-situ fibre-optic distributed temperature sensor system deployed in the uppermost 10 cm of sediment spanning the investigated reach. To determine changes

  15. Effect of DSPE-PEG on compound action potential, injury potential and ion concentration following compression in ex vivo spinal cord.

    PubMed

    Wang, Aihua; Huo, Xiaolin; Zhang, Guanghao; Wang, Xiaochen; Zhang, Cheng; Wu, Changzhe; Rong, Wei; Xu, Jing; Song, Tao

    2016-05-01

    It has been shown that polyethylene glycol (PEG) can reseal membrane disruption on the spinal cord, but only high concentrations of PEG have been shown to have this effect. Therefore, the effect of PEG is somewhat limited, and it is necessary to investigate a new approach to repair spinal cord injury. This study assesses the ability of 1, 2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(poly (ethylene glycol)) 2000] (DSPE-PEG) to recover physiological function and attenuate the injury-induced influx of extracellular ions in ex vivo spinal cord injury. Isolated spinal cords were subjected to compression injury and treated with PEG or DSPE-PEG immediately after injury. The compound action potential (CAP) was recorded before and after injury to assess the functional recovery. Furthermore, injury potential, the difference in gap potentials before and after compression, and the concentration of intracellular ions were used to evaluate the effect of DSPE-PEG on reducing ion influx. Data showed that the injury potential and ion concentration of the untreated, PEG and DSPE-PEG group, without significant difference among them, are remarkably higher than those of the intact group. Moreover, the CAP recovery of the DSPE-PEG and PEG treated spinal cords was significantly greater than that of the untreated spinal cords. The level of CAP recovery in the DSPE-PEG and PEG treated groups was the same, but the concentration of DSPE-PEG used was much lower than the concentration of PEG. These results suggest that instant application of DSPE-PEG could effectively repair functional disturbance in SCI at a much lower concentration than PEG.

  16. Ajoene, the antiplatelet principle of garlic, synergistically potentiates the antiaggregatory action of prostacyclin, forskolin, indomethacin and dypiridamole on human platelets.

    PubMed

    Apitz-Castro, R; Escalante, J; Vargas, R; Jain, M K

    1986-05-01

    Ajoene, the major antiplatelet compound derived from garlic, synergistically potentiates the antiaggregatory action of prostacyclin, forskolin, indomethacin and dypiridamole. For collagen-induced platelet aggregation in human PRP, the ID50 for ajoene is 95 +/- 5 microM. However, in the presence of the antiaggregatory drugs mentioned above, the ID50 for ajoene decreases more than what would be predicted on the basis of simple additive effects. Similarly, the ID50 for prostacyclin decreases from 1 nM to 0.15 nM in the presence of 80 microM ajoene. Isobolic curves for the various combinations of ajoene with prostacyclin or indomethacin exhibit departure from linearity, as predicted for a potentiated synergism between ajoene and these drugs. Dypiridamole, which in PRP has very little effect on the dose-response curve for ajoene, when assayed in whole blood decreases the ID50 for ajoene by a factor of four. These results demonstrate that the antithrombotic potential of ajoene is substantially increased in the presence of physiologically and pharmacologically active antiplatelet agents.

  17. Promoting HIV Vaccine Research in African American Communities: Does the Theory of Reasoned Action Explain Potential Outcomes of Involvement?

    PubMed

    Frew, Paula M; Archibald, Matthew; Martinez, Nina; del Rio, Carlos; Mulligan, Mark J

    2007-01-01

    The HIV/AIDS pandemic continues to challenge the African American community with disproportionate rates of infection, particularly among young women ages 25 to 34 years. Development of a preventive HIV vaccine may bring a substantial turning point in this health crisis. Engagement of the African American community is necessary to improve awareness of the effort and favorably influence attitudes and referent norms. The Theory of Reasoned Action (TRA) may be a useful framework for exploration of community engagement outcomes including future attendance, community mobilization, and study participation. Within the context of HIV vaccine outreach, we conducted a cross-sectional survey in early 2007 with 175 African-American adults (>/= 18 years). Confirmatory factor analysis and structural equation modeling were performed and the findings support the potential of the model in understanding behavioral intentions toward HIV vaccine research.

  18. Encoding for computation: Recognizing brief dynamical patterns by exploiting effects of weak rhythms on action-potential timing

    PubMed Central

    Hopfield, J. J.

    2004-01-01

    Many stimuli have meaning only as patterns over time. Most auditory and many visual stimuli are of this nature and can be described as multidimensional, time-dependent vectors. A simple neuron can encode a single component of the vector in a firing rate. The addition of a small subthreshold oscillatory current perturbs the action-potential timing, encoding the signal also in a timing relationship, with little effect on the coexisting firing rate representation. When the subthreshold signal is common to a group of neurons, the timing-based information is significant to neurons receiving inputs from the group. This information encoding allows simple implementation of computations not readily done with rate coding. These ideas are examined by using speech to provide a realistic input signal to a biologically inspired model network of spiking neurons. The output neurons of the two-layer system are shown to specifically encode short linguistic elements of speech. PMID:15075391

  19. Dendritic Na(+) spikes enable cortical input to drive action potential output from hippocampal CA2 pyramidal neurons.

    PubMed

    Sun, Qian; Srinivas, Kalyan V; Sotayo, Alaba; Siegelbaum, Steven A

    2014-01-01

    Synaptic inputs from different brain areas are often targeted to distinct regions of neuronal dendritic arbors. Inputs to proximal dendrites usually produce large somatic EPSPs that efficiently trigger action potential (AP) output, whereas inputs to distal dendrites are greatly attenuated and may largely modulate AP output. In contrast to most other cortical and hippocampal neurons, hippocampal CA2 pyramidal neurons show unusually strong excitation by their distal dendritic inputs from entorhinal cortex (EC). In this study, we demonstrate that the ability of these EC inputs to drive CA2 AP output requires the firing of local dendritic Na(+) spikes. Furthermore, we find that CA2 dendritic geometry contributes to the efficient coupling of dendritic Na(+) spikes to AP output. These results provide a striking example of how dendritic spikes enable direct cortical inputs to overcome unfavorable distal synaptic locale to trigger axonal AP output and thereby enable efficient cortico-hippocampal information flow.

  20. Nerve-released acetylcholine contracts urinary bladder smooth muscle by inducing action potentials independently of IP3-mediated calcium release.

    PubMed

    Nausch, Bernhard; Heppner, Thomas J; Nelson, Mark T

    2010-09-01

    Nerve-released ACh is the main stimulus for contraction of urinary bladder smooth muscle (UBSM). Here, the mechanisms by which ACh contracts UBSM are explored by determining Ca(2+) and electrical signals induced by nerve-released ACh. Photolysis of caged inositol 1,4,5-trisphosphate (IP(3)) evoked Ca(2+) release from the sarcoplasmic reticulum. Electrical field stimulation (20 Hz) induced Ca(2+) waves within the smooth muscle that were present only during stimulus application. Ca(2+) waves were blocked by inhibition of muscarinic ACh receptors (mAChRs) with atropine and depletion of sarcoplasmic reticulum Ca(2+) stores with cyclopiazonic acid (CPA), and therefore likely reflect activation of IP(3) receptors (IP(3)Rs). Electrical field stimulation also increased excitability to induce action potentials (APs) that were accompanied by Ca(2+) flashes, reflecting Ca(2+) entry through voltage-dependent Ca(2+) channels (VDCCs) during the action potential. The evoked Ca(2+) flashes and APs occurred as a burst with a lag time of approximately 1.5 s after onset of stimulation. They were not inhibited by blocking IP(3)-mediated Ca(2+) waves, but by blockers of mAChRs (atropine) and VDCCs (diltiazem). Nerve-evoked contractions of UBSM strips were greatly reduced by blocking VDCCs, but not by preventing IP(3)-mediated Ca(2+) signaling with cyclopiazonic acid or inhibition of PLC with U73122. These results indicate that ACh released from nerve varicosities induces IP(3)-mediated Ca(2+) waves during stimulation; but contrary to expectations, these signals do not appear to participate in contraction. In addition, our data provide compelling evidence that UBSM contractions evoked by nerve-released ACh depend on increased excitability and the resultant Ca(2+) entry through VDCCs during APs.