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  1. Book ; Conference proceedings ; Collection: Agora Meeting on Fluctuations in Biological Systems

    Århem, Peter

    Sigtuna, Sweden, August 3 -7, 1999

    2001  

    Event/congress Meeting on Fluctuations in Biological Systems (4, 1999, Sigtuna)
    Author's details guest ed.: P. Århem
    Language English
    Dates of publication 2001-9999
    Publisher Elsevier
    Publishing place Amsterdam u.a.
    Publishing country Netherlands
    Document type Book ; Conference proceedings ; Collection (display volumes)
    HBZ-ID HT013183758
    Database Catalogue ZB MED Medicine, Health

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  2. Book ; Conference proceedings: Agora Meeting on Fluctuations in Biological Systems / 2

    Århem, Peter

    Sigtuna, Sweden, August 3 -7, 1999

    (BioSystems ; 63,1/3 : Special issue)

    2001  

    Event/congress Meeting on Fluctuations in Biological Systems (4, 1999, Sigtuna)
    Author's details guest ed.: P. Århem
    Series title BioSystems ; 63,1/3 : Special issue
    Agora Meeting on Fluctuations in Biological Systems
    Biosystems
    Collection Agora Meeting on Fluctuations in Biological Systems
    Biosystems
    Language English
    Size 118 S. : Ill., graph. Darst.
    Publisher Elsevier
    Publishing place Amsterdam u.a.
    Publishing country Netherlands
    Document type Book ; Conference proceedings
    HBZ-ID HT013183785
    Database Catalogue ZB MED Medicine, Health

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    In stock of ZB MED Cologne/Königswinter

    Shelf markLoan statusLocation
    Zs A 768 -63- not available for loan Zeitschriften-Lesesaal

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  3. Book ; Conference proceedings: Agora Meeting on Fluctuations in Biological Systems / 1

    Århem, Peter

    Sigtuna, Sweden, August 3 -7, 1999

    (BioSystems ; 62,1/3 : Special issue)

    2001  

    Event/congress Meeting on Fluctuations in Biological Systems (4, 1999, Sigtuna)
    Author's details guest ed.: P. Århem
    Series title BioSystems ; 62,1/3 : Special issue
    Biosystems
    Agora Meeting on Fluctuations in Biological Systems
    Collection Biosystems
    Agora Meeting on Fluctuations in Biological Systems
    Language English
    Size 138 S. : graph. Darst.
    Publisher Elsevier
    Publishing place Amsterdam u.a.
    Publishing country Netherlands
    Document type Book ; Conference proceedings
    HBZ-ID HT013183777
    Database Catalogue ZB MED Medicine, Health

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Shelf markLoan statusLocation
    Zs A 768 -62- not available for loan Zeitschriften-Lesesaal

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  4. Book ; Conference proceedings: Matter matters?

    Århem, Peter

    on the material basis of the cognitive activity of mind ; [workshops ... of the Swedish Council for Planning and Coordination of Research ... 1993]

    1997  

    Institution Schweden / Forskningsrådsnämnden
    Author's details Peter Århem ... (eds.)
    Keywords Brain / physiology / congresses ; Cognition / physiology / congresses ; Psychophysiology / congresses ; Leib-Seele-Problem ; Neurophysiologie
    Subject Nervenphysiologie ; Nervensystem ; Seele ; Körper ; Körper-Geist-Beziehung ; Körper-Seele-Beziehung ; Leib-Seele-Beziehung ; Psychophysisches Problem ; Leib
    Language English
    Size IX, 269 S. : Ill., graph. Darst.
    Publisher Springer
    Publishing place Berlin u.a.
    Document type Book ; Conference proceedings
    HBZ-ID HT007528163
    ISBN 3-540-61776-0 ; 978-3-540-61776-1
    Database Catalogue ZB MED Medicine, Health

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    In stock of ZB MED Cologne/Königswinter

    Shelf markLoan statusLocation
    1997 A 8920 order for loan Magazin

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  5. Article ; Online: Closed and open state dependent block of potassium channels cause opposing effects on excitability - a computational approach.

    Ågren, Richard / Nilsson, Johanna / Århem, Peter

    Scientific reports

    2019  Volume 9, Issue 1, Page(s) 8175

    Abstract: Block of voltage-gated potassium (Kv) channels has been demonstrated to affect neuronal activity described as increasing excitability. The effect has been associated with a closed-state dependent block. However, the block of Kv channels in e.g. local ... ...

    Abstract Block of voltage-gated potassium (Kv) channels has been demonstrated to affect neuronal activity described as increasing excitability. The effect has been associated with a closed-state dependent block. However, the block of Kv channels in e.g. local anesthetic and antiarrhythmics, is open state-dependent. Since the reduced excitability in this case mainly is due to sodium channel block, the role of the Kv channel block is concealed. The present investigation aims to analyse the specific role of state-dependent Kv channel block for excitability. Using a computational approach, with introduced blocked states in the Kv channel of the Frankenhaeuser-Huxley axon membrane model, we calculated the effects on threshold, firing and presynaptic Ca influx. The Ca influx was obtained from an N-type Cav channel model linked to the Frankenhaeuser-Huxley membrane. The results suggested that a selective block of open Kv channels decreased the rate of repetitive firing and the consequent Ca influx, thus challenging the traditional view. In contrast, presence of a closed-state block, increased the firing rate and the Ca influx. These findings propose that Kv channel block may either increase or decrease cellular excitability, thus highlighting the importance of further investigating the role of state-specific blocking mechanisms.
    MeSH term(s) Action Potentials/physiology ; Animals ; Axons/metabolism ; Biophysical Phenomena ; Calcium/metabolism ; Computational Biology ; Humans ; Ion Channel Gating/drug effects ; Ion Channel Gating/physiology ; Membranes/metabolism ; Mice ; Models, Theoretical ; Neurons/drug effects ; Neurons/physiology ; Potassium/metabolism ; Potassium Channel Blockers/chemistry ; Potassium Channels, Voltage-Gated/antagonists & inhibitors ; Potassium Channels, Voltage-Gated/chemistry ; Potassium Channels, Voltage-Gated/metabolism ; Xenopus laevis/metabolism ; Xenopus laevis/physiology
    Chemical Substances Potassium Channel Blockers ; Potassium Channels, Voltage-Gated ; Potassium (RWP5GA015D) ; Calcium (SY7Q814VUP)
    Language English
    Publishing date 2019-06-03
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-019-44564-x
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  6. Article ; Online: Point mutation of a conserved aspartate, D69, in the muscarinic M

    Ågren, Richard / Sahlholm, Kristoffer / Nilsson, Johanna / Århem, Peter

    Biochemical and biophysical research communications

    2018  Volume 496, Issue 1, Page(s) 101–104

    Abstract: The muscarinic ... ...

    Abstract The muscarinic M
    MeSH term(s) Acetylcholine/administration & dosage ; Animals ; Aspartic Acid/genetics ; Cells, Cultured ; Conserved Sequence ; Dose-Response Relationship, Drug ; G Protein-Coupled Inwardly-Rectifying Potassium Channels/metabolism ; Membrane Potentials/drug effects ; Membrane Potentials/physiology ; Mutagenesis, Site-Directed ; Oocytes ; Point Mutation/genetics ; Receptor, Muscarinic M2/drug effects ; Receptor, Muscarinic M2/genetics ; Receptor, Muscarinic M2/metabolism ; Structure-Activity Relationship ; Xenopus laevis
    Chemical Substances G Protein-Coupled Inwardly-Rectifying Potassium Channels ; Receptor, Muscarinic M2 ; Aspartic Acid (30KYC7MIAI) ; Acetylcholine (N9YNS0M02X)
    Language English
    Publishing date 2018--29
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 205723-2
    ISSN 1090-2104 ; 0006-291X ; 0006-291X
    ISSN (online) 1090-2104 ; 0006-291X
    ISSN 0006-291X
    DOI 10.1016/j.bbrc.2018.01.005
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 116: Show issues Location:
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  7. Article: The Importance of the Dissociation Rate in Ion Channel Blocking.

    Zeberg, Hugo / Nilsson, Johanna / Århem, Peter

    Frontiers in cellular neuroscience

    2018  Volume 12, Page(s) 33

    Abstract: Understanding the relationships between the rates and dynamics of current wave forms under voltage clamp conditions is essential for understanding phenomena such as state-dependence and use-dependence, which are fundamental for the action of drugs used ... ...

    Abstract Understanding the relationships between the rates and dynamics of current wave forms under voltage clamp conditions is essential for understanding phenomena such as state-dependence and use-dependence, which are fundamental for the action of drugs used as anti-epileptics, anti-arrhythmics, and anesthetics. In the present study, we mathematically analyze models of blocking mechanisms. In previous experimental studies of potassium channels we have shown that the effect of local anesthetics can be explained by binding to channels in the open state. We therefore here examine models that describe the effect of a blocking drug that binds to a non-inactivating channel in its open state. Such binding induces an inactivation-like current decay at higher potential steps. The amplitude of the induced peak depends on voltage and concentration of blocking drug. In the present study, using analytical methods, we (i) derive a criterion for the existence of a peak in the open probability time evolution for a model with an arbitrary number of closed states, (ii) derive formula for the relative height of the peak amplitude, and (iii) determine the voltage dependence of the relative peak height. Two findings are apparent: (1) the dissociation (unbinding) rate constant is important for the existence of a peak in the current waveform, while the association (binding) rate constant is not, and (2) for a peak to exist it suffices that the dissociation rate must be smaller than the absolute value of all eigenvalues to the kinetic matrix describing the model.
    Language English
    Publishing date 2018-02-09
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2452963-1
    ISSN 1662-5102
    ISSN 1662-5102
    DOI 10.3389/fncel.2018.00033
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  8. Article ; Online: The Beta-Arrestin-Biased Dopamine D2 Receptor Ligand, UNC9994, Is a Partial Agonist at G-Protein-Mediated Potassium Channel Activation.

    Ågren, Richard / Århem, Peter / Nilsson, Johanna / Sahlholm, Kristoffer

    The international journal of neuropsychopharmacology

    2018  Volume 21, Issue 12, Page(s) 1102–1108

    Abstract: Background: Previous evidence suggests that UNC9994 is a beta-arrestin2-selective agonist at the dopamine D2 receptor, lacking ability both to activate and antagonize G protein-dependent signaling. However, this has only been reported by one laboratory ... ...

    Abstract Background: Previous evidence suggests that UNC9994 is a beta-arrestin2-selective agonist at the dopamine D2 receptor, lacking ability both to activate and antagonize G protein-dependent signaling. However, this has only been reported by one laboratory using a single assay.
    Methods: We used G protein-coupled inward rectifier potassium channel activation in Xenopus oocytes to investigate UNC9994-induced modulation of G protein-dependent signaling at dopamine D2 receptor and dopamine D3 receptor.
    Results: At dopamine D2 receptor, UNC9994 induced G protein-coupled inward rectifier potassium channel currents that were 15% of the maximal response to dopamine, with an EC50 of 185 nM. At dopamine D3 receptor, the ligand elicited 89% of the maximal dopamine response with an EC50 of 62 nM. Pertussis toxin abolished G protein-coupled inward rectifier potassium channel activation. Furthermore, UNC9994 antagonized dopamine-induced G protein-coupled inward rectifier potassium channel activation at dopamine D2 receptor.
    Conclusions: UNC9994 modulates G protein-coupled inward rectifier potassium channel channel activation via pertussis toxin-sensitive G proteins at dopamine D2 receptor and dopamine D3 receptor. These findings may have implications for the interpretation of data obtained with this ligand.
    MeSH term(s) Animals ; Antipsychotic Agents/pharmacology ; G Protein-Coupled Inwardly-Rectifying Potassium Channels/drug effects ; Humans ; Ligands ; Oocytes ; Receptors, Dopamine D2 ; Receptors, Dopamine D3 ; Signal Transduction/drug effects ; Xenopus laevis ; beta-Arrestin 2
    Chemical Substances Antipsychotic Agents ; G Protein-Coupled Inwardly-Rectifying Potassium Channels ; Ligands ; Receptors, Dopamine D2 ; Receptors, Dopamine D3 ; beta-Arrestin 2
    Language English
    Publishing date 2018-07-07
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1440129-0
    ISSN 1469-5111 ; 1461-1457
    ISSN (online) 1469-5111
    ISSN 1461-1457
    DOI 10.1093/ijnp/pyy059
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 5187: Show issues Location:
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  9. Article ; Online: Closed and open state dependent block of potassium channels cause opposing effects on excitability – a computational approach

    Richard Ågren / Johanna Nilsson / Peter Århem

    Scientific Reports, Vol 9, Iss 1, Pp 1-

    2019  Volume 10

    Abstract: Abstract Block of voltage-gated potassium (Kv) channels has been demonstrated to affect neuronal activity described as increasing excitability. The effect has been associated with a closed-state dependent block. However, the block of Kv channels in e.g. ... ...

    Abstract Abstract Block of voltage-gated potassium (Kv) channels has been demonstrated to affect neuronal activity described as increasing excitability. The effect has been associated with a closed-state dependent block. However, the block of Kv channels in e.g. local anesthetic and antiarrhythmics, is open state-dependent. Since the reduced excitability in this case mainly is due to sodium channel block, the role of the Kv channel block is concealed. The present investigation aims to analyse the specific role of state-dependent Kv channel block for excitability. Using a computational approach, with introduced blocked states in the Kv channel of the Frankenhaeuser-Huxley axon membrane model, we calculated the effects on threshold, firing and presynaptic Ca influx. The Ca influx was obtained from an N-type Cav channel model linked to the Frankenhaeuser-Huxley membrane. The results suggested that a selective block of open Kv channels decreased the rate of repetitive firing and the consequent Ca influx, thus challenging the traditional view. In contrast, presence of a closed-state block, increased the firing rate and the Ca influx. These findings propose that Kv channel block may either increase or decrease cellular excitability, thus highlighting the importance of further investigating the role of state-specific blocking mechanisms.
    Keywords Medicine ; R ; Science ; Q
    Subject code 003
    Language English
    Publishing date 2019-06-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  10. Article ; Online: Extracellular Linkers Completely Transplant the Voltage Dependence from Kv1.2 Ion Channels to Kv2.1.

    Elinder, Fredrik / Madeja, Michael / Zeberg, Hugo / Århem, Peter

    Biophysical journal

    2016  Volume 111, Issue 8, Page(s) 1679–1691

    Abstract: The transmembrane voltage needed to open different voltage-gated K (Kv) channels differs by up to 50 mV from each other. In this study we test the hypothesis that the channels' voltage dependences to a large extent are set by charged amino-acid residues ... ...

    Abstract The transmembrane voltage needed to open different voltage-gated K (Kv) channels differs by up to 50 mV from each other. In this study we test the hypothesis that the channels' voltage dependences to a large extent are set by charged amino-acid residues of the extracellular linkers of the Kv channels, which electrostatically affect the charged amino-acid residues of the voltage sensor S4. Extracellular cations shift the conductance-versus-voltage curve, G(V), by interfering with these extracellular charges. We have explored these issues by analyzing the effects of the divalent strontium ion (Sr
    MeSH term(s) Animals ; Cell Membrane/metabolism ; Electrophysiological Phenomena ; Evolution, Molecular ; Extracellular Space/metabolism ; Kv1.2 Potassium Channel/metabolism ; Xenopus
    Chemical Substances Kv1.2 Potassium Channel
    Language English
    Publishing date 2016-10-18
    Publishing country United States
    Document type Journal Article
    ZDB-ID 218078-9
    ISSN 1542-0086 ; 0006-3495
    ISSN (online) 1542-0086
    ISSN 0006-3495
    DOI 10.1016/j.bpj.2016.08.043
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