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  1. Article ; Online: Neuronal and Cardiovascular Potassium Channels as Therapeutic Drug Targets: Promise and Pitfalls.

    Humphries, Edward S A / Dart, Caroline

    Journal of biomolecular screening

    2015  Volume 20, Issue 9, Page(s) 1055–1073

    Abstract: Potassium (K(+)) channels, with their diversity, often tissue-defined distribution, and critical role in controlling cellular excitability, have long held promise of being important drug targets for the treatment of dysrhythmias in the heart and abnormal ...

    Abstract Potassium (K(+)) channels, with their diversity, often tissue-defined distribution, and critical role in controlling cellular excitability, have long held promise of being important drug targets for the treatment of dysrhythmias in the heart and abnormal neuronal activity within the brain. With the exception of drugs that target one particular class, ATP-sensitive K(+) (KATP) channels, very few selective K(+) channel activators or inhibitors are currently licensed for clinical use in cardiovascular and neurological disease. Here we review what a range of human genetic disorders have told us about the role of specific K(+) channel subunits, explore the potential of activators and inhibitors of specific channel populations as a therapeutic strategy, and discuss possible reasons for the difficulty in designing clinically relevant K(+) channel modulators.
    MeSH term(s) Animals ; Cardiovascular Agents/pharmacology ; Cardiovascular Agents/therapeutic use ; Cardiovascular Diseases/drug therapy ; Cardiovascular Diseases/metabolism ; Humans ; Myocardium/metabolism ; Nervous System Diseases/drug therapy ; Nervous System Diseases/metabolism ; Neurons/metabolism ; Potassium Channel Blockers/pharmacology ; Potassium Channel Blockers/therapeutic use ; Potassium Channels/physiology
    Chemical Substances Cardiovascular Agents ; Potassium Channel Blockers ; Potassium Channels
    Language English
    Publishing date 2015-08-24
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 1433680-7
    ISSN 1552-454X ; 1087-0571
    ISSN (online) 1552-454X
    ISSN 1087-0571
    DOI 10.1177/1087057115601677
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 4911: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

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  2. Article: Neuronal and Cardiovascular Potassium Channels as Therapeutic Drug Targets: Promise and Pitfalls

    Humphries, Edward S.A. / Dart, Caroline

    Society for Laboratory Automation and Screening SLAS discovery. 2015 Oct., v. 20, no. 9

    2015  

    Abstract: Potassium (K⁺) channels, with their diversity, often tissue-defined distribution, and critical role in controlling cellular excitability, have long held promise of being important drug targets for the treatment of dysrhythmias in the heart and abnormal ... ...

    Abstract Potassium (K⁺) channels, with their diversity, often tissue-defined distribution, and critical role in controlling cellular excitability, have long held promise of being important drug targets for the treatment of dysrhythmias in the heart and abnormal neuronal activity within the brain. With the exception of drugs that target one particular class, ATP-sensitive K⁺ (KATP) channels, very few selective K⁺ channel activators or inhibitors are currently licensed for clinical use in cardiovascular and neurological disease. Here we review what a range of human genetic disorders have told us about the role of specific K⁺ channel subunits, explore the potential of activators and inhibitors of specific channel populations as a therapeutic strategy, and discuss possible reasons for the difficulty in designing clinically relevant K⁺ channel modulators.
    Keywords brain ; drugs ; heart ; humans ; nervous system diseases ; neurons ; potassium ; therapeutics
    Language English
    Dates of publication 2015-10
    Size p. 1055-1073.
    Publishing place Elsevier Inc.
    Document type Article
    ZDB-ID 2885123-7
    ISSN 2472-5560 ; 2472-5552
    ISSN (online) 2472-5560
    ISSN 2472-5552
    DOI 10.1177/1087057115601677
    Database NAL-Catalogue (AGRICOLA)

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 4911: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

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  3. Article ; Online: Calcium/calmodulin-dependent kinase 2 mediates Epac-induced spontaneous transient outward currents in rat vascular smooth muscle.

    Humphries, Edward S A / Kamishima, Tomoko / Quayle, John M / Dart, Caroline

    The Journal of physiology

    2017  Volume 595, Issue 18, Page(s) 6147–6164

    Abstract: Key points: The Ca: Abstract: Activation of the major cAMP effector, exchange protein directly activated by cAMP (Epac), induces vascular smooth muscle relaxation by increasing the activity of ryanodine (RyR)-sensitive release channels on the ... ...

    Abstract Key points: The Ca
    Abstract: Activation of the major cAMP effector, exchange protein directly activated by cAMP (Epac), induces vascular smooth muscle relaxation by increasing the activity of ryanodine (RyR)-sensitive release channels on the peripheral sarcoplasmic reticulum. Resultant Ca
    MeSH term(s) Action Potentials ; Animals ; Calcium/metabolism ; Calcium-Calmodulin-Dependent Protein Kinase Type 2/genetics ; Calcium-Calmodulin-Dependent Protein Kinase Type 2/metabolism ; Cells, Cultured ; Guanine Nucleotide Exchange Factors/metabolism ; Large-Conductance Calcium-Activated Potassium Channels/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Muscle, Smooth, Vascular/cytology ; Muscle, Smooth, Vascular/metabolism ; Muscle, Smooth, Vascular/physiology ; Myocytes, Smooth Muscle/metabolism ; Rats ; Rats, Wistar ; Vasodilation
    Chemical Substances Guanine Nucleotide Exchange Factors ; Large-Conductance Calcium-Activated Potassium Channels ; Calcium-Calmodulin-Dependent Protein Kinase Type 2 (EC 2.7.11.17) ; Calcium (SY7Q814VUP)
    Language English
    Publishing date 2017-08-14
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 3115-x
    ISSN 1469-7793 ; 0022-3751
    ISSN (online) 1469-7793
    ISSN 0022-3751
    DOI 10.1113/JP274754
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: There is no F in APC: Using physiological fluoride-free solutions for high throughput automated patch clamp experiments.

    Rapedius, Markus / Obergrussberger, Alison / Humphries, Edward S A / Scholz, Stephanie / Rinke-Weiss, Ilka / Goetze, Tom A / Brinkwirth, Nina / Rotordam, Maria Giustina / Strassmaier, Tim / Randolph, Aaron / Friis, Søren / Liutkute, Aiste / Seibertz, Fitzwilliam / Voigt, Niels / Fertig, Niels

    Frontiers in molecular neuroscience

    2022  Volume 15, Page(s) 982316

    Abstract: Fluoride has been used in the internal recording solution for manual and automated patch clamp experiments for decades because it helps to improve the seal resistance and promotes longer lasting recordings. In manual patch clamp, fluoride has been used ... ...

    Abstract Fluoride has been used in the internal recording solution for manual and automated patch clamp experiments for decades because it helps to improve the seal resistance and promotes longer lasting recordings. In manual patch clamp, fluoride has been used to record voltage-gated Na (Na
    Language English
    Publishing date 2022-08-22
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2452967-9
    ISSN 1662-5099
    ISSN 1662-5099
    DOI 10.3389/fnmol.2022.982316
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Quantitative proteomics characterization of acutely isolated primary adult rat cardiomyocytes and fibroblasts.

    Poulsen, Pi Camilla / Schrölkamp, Maren / Bagwan, Navratan / Leurs, Ulrike / Humphries, Edward S A / Bomholzt, Sofia Hammami / Nielsen, Morten Schak / Bentzen, Bo Hjorth / Olsen, Jesper Velgaard / Lundby, Alicia

    Journal of molecular and cellular cardiology

    2020  Volume 143, Page(s) 63–70

    Abstract: Our heart is comprised of many different cell types that all contribute to cardiac function. An important step in deciphering the molecular complexity of our heart is to decipher the molecular composition of the various cardiac cell types. Here we set ... ...

    Abstract Our heart is comprised of many different cell types that all contribute to cardiac function. An important step in deciphering the molecular complexity of our heart is to decipher the molecular composition of the various cardiac cell types. Here we set out to delineate a comprehensive protein expression profile of the two most prevalent cell types in the heart: cardiomyocytes and cardiac fibroblasts. To this end, we isolated cardiomyocytes and fibroblasts from rat hearts and combined state-of-the-art flow cytometry with high-resolution mass spectrometry to investigate their proteome profiles right after isolation. We measured and quantified 5240 proteins in cardiomyocytes and 6328 proteins in cardiac fibroblasts. In addition to providing a global protein profile for these cardiac cell types, we also present specific findings, such as unique expression of ion channels and transcription factors for each cell type. For instance, we show that the sodium channel Scn7a and the cation channel Trpm7 are expressed in fibroblasts but not in cardiomyocytes, which underscores the importance of investigating the endogenous cell host prior to functional studies. Our dataset represents a valuable resource on protein expression profiles in these two primary cardiac cells types.
    Language English
    Publishing date 2020-04-20
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 80157-4
    ISSN 1095-8584 ; 0022-2828
    ISSN (online) 1095-8584
    ISSN 0022-2828
    DOI 10.1016/j.yjmcc.2020.04.021
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 426: Show issues Location:
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  6. Article ; Online: Publisher Correction: Cross-site and cross-platform variability of automated patch clamp assessments of drug effects on human cardiac currents in recombinant cells.

    Kramer, James / Himmel, Herbert M / Lindqvist, Anders / Stoelzle-Feix, Sonja / Chaudhary, Khuram W / Li, Dingzhou / Bohme, Georg Andrees / Bridgland-Taylor, Matthew / Hebeisen, Simon / Fan, Jingsong / Renganathan, Muthukrishnan / Imredy, John / Humphries, Edward S A / Brinkwirth, Nina / Strassmaier, Tim / Ohtsuki, Atsushi / Danker, Timm / Vanoye, Carlos / Polonchuk, Liudmila /
    Fermini, Bernard / Pierson, Jennifer Beck / Gintant, Gary

    Scientific reports

    2020  Volume 10, Issue 1, Page(s) 11884

    Abstract: An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...

    Abstract An amendment to this paper has been published and can be accessed via a link at the top of the paper.
    Language English
    Publishing date 2020-07-14
    Publishing country England
    Document type Published Erratum
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-020-68819-0
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Cross-site and cross-platform variability of automated patch clamp assessments of drug effects on human cardiac currents in recombinant cells.

    Kramer, James / Himmel, Herbert M / Lindqvist, Anders / Stoelzle-Feix, Sonja / Chaudhary, Khuram W / Li, Dingzhou / Bohme, Georg Andrees / Bridgland-Taylor, Matthew / Hebeisen, Simon / Fan, Jingsong / Renganathan, Muthukrishnan / Imredy, John / Humphries, Edward S A / Brinkwirth, Nina / Strassmaier, Tim / Ohtsuki, Atsushi / Danker, Timm / Vanoye, Carlos / Polonchuk, Liudmila /
    Fermini, Bernard / Pierson, Jennifer Beck / Gintant, Gary

    Scientific reports

    2020  Volume 10, Issue 1, Page(s) 5627

    Abstract: Automated patch clamp (APC) instruments enable efficient evaluation of electrophysiologic effects of drugs on human cardiac currents in heterologous expression systems. Differences in experimental protocols, instruments, and dissimilar site procedures ... ...

    Abstract Automated patch clamp (APC) instruments enable efficient evaluation of electrophysiologic effects of drugs on human cardiac currents in heterologous expression systems. Differences in experimental protocols, instruments, and dissimilar site procedures affect the variability of IC
    Language English
    Publishing date 2020-03-27
    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/s41598-020-62344-w
    Database MEDical Literature Analysis and Retrieval System OnLINE

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