liu.seSearch for publications in DiVA
Change search
Refine search result
1 - 6 of 6
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Rows per page
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sort
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
Select
The maximal number of hits you can export is 250. When you want to export more records please use the Create feeds function.
  • 1.
    Jakesova, Marie
    et al.
    Linköping University, Department of Science and Technology, Laboratory of Organic Electronics. Linköping University, Faculty of Science & Engineering.
    Silverå Ejneby, Malin
    Linköping University, Department of Clinical and Experimental Medicine, Divison of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences.
    Derek, Vedran
    Linköping University, Department of Science and Technology, Laboratory of Organic Electronics. Linköping University, Faculty of Science & Engineering.
    Schmidt, Tony
    Med Univ Graz, Austria.
    Gryszel, Maciej
    Linköping University, Department of Science and Technology, Laboratory of Organic Electronics. Linköping University, Faculty of Science & Engineering.
    Brask, Johan
    Linköping University, Department of Clinical and Experimental Medicine, Divison of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences.
    Schindl, Rainer
    Med Univ Graz, Austria.
    Simon, Daniel
    Linköping University, Department of Science and Technology, Laboratory of Organic Electronics. Linköping University, Faculty of Science & Engineering.
    Berggren, Magnus
    Linköping University, Department of Science and Technology, Laboratory of Organic Electronics. Linköping University, Faculty of Science & Engineering.
    Elinder, Fredrik
    Linköping University, Department of Clinical and Experimental Medicine, Divison of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences.
    Glowacki, Eric
    Linköping University, Department of Science and Technology, Laboratory of Organic Electronics. Linköping University, Faculty of Science & Engineering.
    Optoelectronic control of single cells using organic photocapacitors2019In: Science Advances, E-ISSN 2375-2548, Vol. 5, no 4, article id eaav5265Article in journal (Refereed)
    Abstract [en]

    Optical control of the electrophysiology of single cells can be a powerful tool for biomedical research and technology. Here, we report organic electrolytic photocapacitors (OEPCs), devices that function as extracellular capacitive electrodes for stimulating cells. OEPCs consist of transparent conductor layers covered with a donor-acceptor bilayer of organic photoconductors. This device produces an open-circuit voltage in a physiological solution of 330 mV upon illumination using light in a tissue transparency window of 630 to 660 nm. We have performed electrophysiological recordings on Xenopus laevis oocytes, finding rapid (time constants, 50 mu s to 5 ms) photoinduced transient changes in the range of 20 to 110 mV. We measure photoinduced opening of potassium channels, conclusively proving that the OEPC effectively depolarizes the cell membrane. Our results demonstrate that the OEPC can be a versatile nongenetic technique for optical manipulation of electrophysiology and currently represents one of the simplest and most stable and efficient optical stimulation solutions.

  • 2.
    Liin, Sara
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. University of Miami, FL 33136 USA.
    Silverå Ejneby, Malin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Barro-Soria, Rene
    University of Miami, FL 33136 USA.
    Alexander Skarsfeldt, Mark
    University of Copenhagen, Denmark; University of Copenhagen, Denmark.
    Larsson, Johan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. University of Miami, FL 33136 USA.
    Starck Härlin, Frida
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. University of Miami, FL 33136 USA.
    Parkkari, Teija
    University of Eastern Finland, Finland.
    Hjorth Bentzen, Bo
    University of Copenhagen, Denmark; University of Copenhagen, Denmark.
    Schmitt, Nicole
    University of Copenhagen, Denmark; University of Copenhagen, Denmark.
    Peter Larsson, H.
    University of Miami, FL 33136 USA.
    Elinder, Fredrik
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Polyunsaturated fatty acid analogs act antiarrhythmically on the cardiac I-Ks channel2015In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 112, no 18, p. 5714-5719Article in journal (Refereed)
    Abstract [en]

    Polyunsaturated fatty acids (PUFAs) affect cardiac excitability. Kv7.1 and the beta-subunit KCNE1 form the cardiac I-Ks channel that is central for cardiac repolarization. In this study, we explore the prospects of PUFAs as I-Ks channel modulators. We report that PUFAs open Kv7.1 via an electrostatic mechanism. Both the polyunsaturated acyl tail and the negatively charged carboxyl head group are required for PUFAs to open Kv7.1. We further show that KCNE1 coexpression abolishes the PUFA effect on Kv7.1 by promoting PUFA protonation. PUFA analogs with a decreased pK(a) value, to preserve their negative charge at neutral pH, restore the sensitivity to open I-Ks channels. PUFA analogs with a positively charged head group inhibit I-Ks channels. These different PUFA analogs could be developed into drugs to treat cardiac arrhythmias. In support of this possibility, we show that PUFA analogs act antiarrhythmically in embryonic rat cardiomyocytes and in isolated perfused hearts from guinea pig.

  • 3.
    Salari, Sajjad
    et al.
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology.
    Silverå Ejneby, Malin
    Linköping University, Department of Clinical and Experimental Medicine, Divison of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences.
    Brask, Johan
    Linköping University, Department of Clinical and Experimental Medicine, Divison of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences.
    Elinder, Fredrik
    Linköping University, Department of Clinical and Experimental Medicine, Divison of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences.
    Isopimaric acid - a multi-targeting ion channel modulator reducing excitability and arrhythmicity in a spontaneously beating mouse atrial cell line2018In: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 222, no 1, article id e12895Article in journal (Refereed)
    Abstract [en]

    AimAtrial fibrillation is the most common persistent cardiac arrhythmia, and it is not well controlled by present drugs. Because some resin acids open voltage-gated potassium channels and reduce neuronal excitability, we explored the effects of the resin acid isopimaric acid (IPA) on action potentials and ion currents in cardiomyocytes. MethodsSpontaneously beating mouse atrial HL-1 cells were investigated with the whole-cell patch-clamp technique. Results1-25 mol L-1 IPA reduced the action potential frequency by up to 50%. The effect of IPA on six different voltage-gated ion channels was investigated; most voltage-dependent parameters of ion channel gating were shifted in the negative direction along the voltage axis, consistent with a hypothesis that a lipophilic and negatively charged compound binds to the lipid membrane close to the positively charged voltage sensor of the ion channels. The major finding was that IPA inactivated sodium channels and L- and T-type calcium channels and activated the rapidly activating potassium channel and the transient outward potassium channel. Computer simulations of IPA effects on all of the ion currents were consistent with a reduced excitability, and they also showed that effects on the Na channel played the largest role to reduce the action potential frequency. Finally, induced arrhythmia in the HL-1 cells was reversed by IPA. ConclusionLow concentrations of IPA reduced the action potential frequency and restored regular firing by altering the voltage dependencies of several voltage-gated ion channels. These findings can form the basis for a new pharmacological strategy to treat atrial fibrillation.

  • 4.
    Sherrell, Peter
    et al.
    Linköping University, Department of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    Cieślar-Pobuda, Artur
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Institute of Automatic Control, Silesian University of Technology, Gliwice, Poland.
    Silverå Ejneby, Malin
    Linköping University, Department of Clinical and Experimental Medicine, Divison of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences.
    Sammalisto, Laura
    Linköping University, Department of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    Gelmi, Amy
    Linköping University, Department of Physics, Chemistry and Biology. Linköping University, Faculty of Science & Engineering.
    de Muinck, Ebo
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Brask, Johan
    Linköping University, Department of Clinical and Experimental Medicine, Divison of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences.
    Jan Los, Marek
    Malopolska Centre of Biotechnology, Jagiellonian University, Kraków, Poland.
    Rafat, Mehrdad
    Linköping University, Department of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    Rational Design of a Conductive Collagen Heart Patch2017In: Macromolecular Bioscience, ISSN 1616-5187, E-ISSN 1616-5195, Vol. 17, no 7, article id 1600446Article in journal (Refereed)
    Abstract [en]

    Cardiovascular diseases, including myocardial infarction, are the cause of significant morbidity and mortality globally. Tissue engineering is a key emerging treatment method for supporting and repairing the cardiac scar tissue caused by myocardial infarction. Creating cell supportive scaffolds that can be directly implanted on a myocardial infarct is an attractive solution. Hydrogels made of collagen are highly biocompatible materials that can be molded into a range of shapes suitable for cardiac patch applications. The addition of mechanically reinforcing materials, carbon nanotubes, at subtoxic levels allows for the collagen hydrogels to be strengthened, up to a toughness of 30 J m-1 and a two to threefold improvement in Youngs' modulus, thus improving their viability as cardiac patch materials. The addition of carbon nanotubes is shown to be both nontoxic to stem cells, and when using single-walled carbon nanotubes, supportive of live, beating cardiac cells, providing a pathway for the further development of a cardiac patch.

  • 5.
    Silverå Ejneby, Malin
    Linköping University, Department of Clinical and Experimental Medicine, Divison of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences.
    Site and Mechanism of Action of Resin Acids on Voltage-Gated Ion Channels2018Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Voltage-gated ion channels are pore-forming membrane proteins that open or close their gates when the voltage across the membrane is changed. They underlie the electrical activity that enables the heart to pump blood and the brain to receive and send signals. Changes in expression, distribution, and functional properties of voltage-gated ion channels can lead to diseases, such as epilepsy, cardiac arrhythmia, and pain-related disorders. Drugs that modulate the function of voltage-gated ion channels control these diseases in some patients, but the existing drugs do not adequately help all patients, and some also have severe side effects.

    Resin acids are common components of pine resins, with a hydrophobic three-ringed motif and a negatively charged carboxyl group. They open big-conductance Ca2+-activated K+ (BK) channels and voltage-gated potassium (KV) channels. We aimed to characterize the binding site and mechanism of action of resin acids on a KV channel and explore the effect of a resin acid by modifying the position and valence of charge of the carboxyl group. We tested the effect on several voltage-gated ion channels, including two KV channels expressed in Xenopus laevis oocytes and several voltage-gated ion channels expressed in cardiomyocytes. For this endeavour different electrophysiological techniques, ion channels, and cell types were used together with chemical synthesis of about 140 resin-acid derivatives, mathematical models, and computer simulations.

    We found that resin acids bind between the lipid bilayer and the Shaker KV channel, in the cleft between transmembrane segment S3 and S4, on the extracellular side of the voltage-sensor domain. This is a fundamentally new interaction site for small-molecule compounds that otherwise usually bind to ion channels in pockets surrounded by water. We also showed that the resin acids open the Shaker KV channel via an electrostatic mechanism, exerted on the positively charged voltage sensor S4. The effect of a resin acid increased when the negatively charged carboxyl group (the effector) and the hydrophobic three-ringed motif (anchor in lipid bilayer) were separated by three atoms: longer stalks decreased the effect. The length rule, in combination with modifications of the anchor, was used to design new resin-acid derivatives that open the human M-type (Kv7.2/7.3) channel. A naturally occurring resin acid also reduced the excitability of cardiomyocytes by affecting the voltage-dependence of several voltage-gated ion channels. The major finding was that the resin acid inactivated sodium and calcium channels, while it activated KV channels at more negative membrane voltages. Computer simulations confirmed that the combined effect on different ion channels reduced the excitability of a cardiomyocyte. Finally, the resin acid reversed induced arrhythmic firing of the cardiomyocytes.

    In conclusion, resin acids are potential drug candidates for diseases such as epilepsy and cardiac arrhythmia: knowing the binding site and mechanism of action can help to fine tune the resin acid to increase the effect, as well as the selectivity.

    List of papers
    1. A drug pocket at the lipid bilayer-potassium channel interface
    Open this publication in new window or tab >>A drug pocket at the lipid bilayer-potassium channel interface
    Show others...
    2017 (English)In: Science Advances, ISSN 0036-8156, E-ISSN 2375-2548, Vol. 3, no 10, article id e1701099Article in journal (Refereed) Published
    Abstract [en]

    Many pharmaceutical drugs against neurological and cardiovascular disorders exert their therapeutic effects by binding to specific sites on voltage-gated ion channels of neurons or cardiomyocytes. To date, all molecules targeting known ion channel sites bind to protein pockets that are mainly surrounded by water. We describe a lipid-protein drug-binding pocket of a potassium channel. We synthesized and electrophysiologically tested 125 derivatives, analogs, and related compounds to dehydroabietic acid. Functional data in combination with docking and molecular dynamics simulations mapped a binding site for small-molecule compounds at the interface between the lipid bilayer and the transmembrane segments S3 and S4 of the voltage-sensor domain. This fundamentally new binding site for small-molecule compounds paves the way for the design of new types of drugs against diseases caused by altered excitability.

    Place, publisher, year, edition, pages
    AMER ASSOC ADVANCEMENT SCIENCE, 2017
    National Category
    Cell and Molecular Biology
    Identifiers
    urn:nbn:se:liu:diva-144164 (URN)10.1126/sciadv.1701099 (DOI)000417998700021 ()29075666 (PubMedID)
    Note

    Funding Agencies|Swedish Research Council; Swedish Brain Foundation; Swedish Heart-Lung Foundation; Swedish National Infrastructure for Computing

    Available from: 2018-01-08 Created: 2018-01-08 Last updated: 2018-05-15
    2. Atom-by-atom tuning of the electrostatic potassium-channel modulator dehydroabietic acid
    Open this publication in new window or tab >>Atom-by-atom tuning of the electrostatic potassium-channel modulator dehydroabietic acid
    Show others...
    2018 (English)In: The Journal of General Physiology, ISSN 0022-1295, E-ISSN 1540-7748, Vol. 150, no 5, p. 731-750Article in journal (Refereed) Published
    Abstract [en]

    Dehydroabietic acid (DHAA) is a naturally occurring component of pine resin that was recently shown to open voltage-gated potassium (KV) channels. The hydrophobic part of DHAA anchors the compound near the channel’s positively charged voltage sensor in a pocket between the channel and the lipid membrane. The negatively charged carboxyl group exerts an electrostatic effect on the channel’s voltage sensor, leading to the channel opening. In this study, we show that the channel-opening effect increases as the length of the carboxyl-group stalk is extended until a critical length of three atoms is reached. Longer stalks render the compounds noneffective. This critical distance is consistent with a simple electrostatic model in which the charge location depends on the stalk length. By combining an effective anchor with the optimal stalk length, we create a compound that opens the human KV7.2/7.3 (M type) potassium channel at a concentration of 1 µM. These results suggest that a stalk between the anchor and the effector group is a powerful way of increasing the potency of a channel-opening drug.

    Place, publisher, year, edition, pages
    New York, United States: Rockefeller Institute for Medical Research, 2018
    National Category
    Physiology
    Identifiers
    urn:nbn:se:liu:diva-147837 (URN)10.1085/jgp.201711965 (DOI)000434417800008 ()2-s2.0-85046705149 (Scopus ID)
    Note

    Funding agencies: Swedish Research Council [2016-02615]; Swedish Heart-Lung Foundation [20150672]; Swedish Brain Foundation [2016-0326]

    Available from: 2018-05-15 Created: 2018-05-15 Last updated: 2018-06-28Bibliographically approved
    3. Isopimaric acid - a multi-targeting ion channel modulator reducing excitability and arrhythmicity in a spontaneously beating mouse atrial cell line
    Open this publication in new window or tab >>Isopimaric acid - a multi-targeting ion channel modulator reducing excitability and arrhythmicity in a spontaneously beating mouse atrial cell line
    2018 (English)In: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 222, no 1, article id e12895Article in journal (Refereed) Published
    Abstract [en]

    AimAtrial fibrillation is the most common persistent cardiac arrhythmia, and it is not well controlled by present drugs. Because some resin acids open voltage-gated potassium channels and reduce neuronal excitability, we explored the effects of the resin acid isopimaric acid (IPA) on action potentials and ion currents in cardiomyocytes. MethodsSpontaneously beating mouse atrial HL-1 cells were investigated with the whole-cell patch-clamp technique. Results1-25 mol L-1 IPA reduced the action potential frequency by up to 50%. The effect of IPA on six different voltage-gated ion channels was investigated; most voltage-dependent parameters of ion channel gating were shifted in the negative direction along the voltage axis, consistent with a hypothesis that a lipophilic and negatively charged compound binds to the lipid membrane close to the positively charged voltage sensor of the ion channels. The major finding was that IPA inactivated sodium channels and L- and T-type calcium channels and activated the rapidly activating potassium channel and the transient outward potassium channel. Computer simulations of IPA effects on all of the ion currents were consistent with a reduced excitability, and they also showed that effects on the Na channel played the largest role to reduce the action potential frequency. Finally, induced arrhythmia in the HL-1 cells was reversed by IPA. ConclusionLow concentrations of IPA reduced the action potential frequency and restored regular firing by altering the voltage dependencies of several voltage-gated ion channels. These findings can form the basis for a new pharmacological strategy to treat atrial fibrillation.

    Place, publisher, year, edition, pages
    Wiley-VCH Verlagsgesellschaft, 2018
    Keywords
    arrhythmia; atrial fibrillation; ion channels; isopimaric acid; patch clamp; resin acid
    National Category
    Cell and Molecular Biology
    Identifiers
    urn:nbn:se:liu:diva-144564 (URN)10.1111/apha.12895 (DOI)000419864000009 ()28514017 (PubMedID)
    Note

    Funding Agencies|Swedish Research Council; Swedish Heart-Lung Foundation; Swedish Brain Foundation; ALF

    Available from: 2018-01-29 Created: 2018-01-29 Last updated: 2018-05-15
  • 6.
    Silverå Ejneby, Malin
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Divison of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences.
    Wu, Xiongyu
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Ottosson, Nina
    Linköping University, Department of Clinical and Experimental Medicine, Divison of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences.
    Münger, E Peter
    Linköping University, Department of Physics, Chemistry and Biology, Theoretical Physics. Linköping University, Faculty of Science & Engineering.
    Lundström, Ingemar
    Linköping University, Department of Physics, Chemistry and Biology, Sensor and Actuator Systems. Linköping University, Faculty of Science & Engineering.
    Konradsson, Peter
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Elinder, Fredrik
    Linköping University, Department of Clinical and Experimental Medicine, Divison of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences.
    Atom-by-atom tuning of the electrostatic potassium-channel modulator dehydroabietic acid2018In: The Journal of General Physiology, ISSN 0022-1295, E-ISSN 1540-7748, Vol. 150, no 5, p. 731-750Article in journal (Refereed)
    Abstract [en]

    Dehydroabietic acid (DHAA) is a naturally occurring component of pine resin that was recently shown to open voltage-gated potassium (KV) channels. The hydrophobic part of DHAA anchors the compound near the channel’s positively charged voltage sensor in a pocket between the channel and the lipid membrane. The negatively charged carboxyl group exerts an electrostatic effect on the channel’s voltage sensor, leading to the channel opening. In this study, we show that the channel-opening effect increases as the length of the carboxyl-group stalk is extended until a critical length of three atoms is reached. Longer stalks render the compounds noneffective. This critical distance is consistent with a simple electrostatic model in which the charge location depends on the stalk length. By combining an effective anchor with the optimal stalk length, we create a compound that opens the human KV7.2/7.3 (M type) potassium channel at a concentration of 1 µM. These results suggest that a stalk between the anchor and the effector group is a powerful way of increasing the potency of a channel-opening drug.

1 - 6 of 6
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf