Self-restoration of cardiac excitation rhythm by anti-arrhythmic ion channel gating
Homeostatic regulation protects organisms against hazardous physiological changes. However, such regulation is limited in certain organs and associated biological processes. For example, the heart fails to self-restore its normal electrical activity once disturbed, as with sustained arrhythmias. Her...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2020-06-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/55921 |
| _version_ | 1811202704721051648 |
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| author | Rupamanjari Majumder Tim De Coster Nina Kudryashova Arie O Verkerk Ivan V Kazbanov Balázs Ördög Niels Harlaar Ronald Wilders Antoine AF de Vries Dirk L Ypey Alexander V Panfilov Daniël A Pijnappels |
| author_facet | Rupamanjari Majumder Tim De Coster Nina Kudryashova Arie O Verkerk Ivan V Kazbanov Balázs Ördög Niels Harlaar Ronald Wilders Antoine AF de Vries Dirk L Ypey Alexander V Panfilov Daniël A Pijnappels |
| author_sort | Rupamanjari Majumder |
| collection | DOAJ |
| description | Homeostatic regulation protects organisms against hazardous physiological changes. However, such regulation is limited in certain organs and associated biological processes. For example, the heart fails to self-restore its normal electrical activity once disturbed, as with sustained arrhythmias. Here we present proof-of-concept of a biological self-restoring system that allows automatic detection and correction of such abnormal excitation rhythms. For the heart, its realization involves the integration of ion channels with newly designed gating properties into cardiomyocytes. This allows cardiac tissue to i) discriminate between normal rhythm and arrhythmia based on frequency-dependent gating and ii) generate an ionic current for termination of the detected arrhythmia. We show in silico, that for both human atrial and ventricular arrhythmias, activation of these channels leads to rapid and repeated restoration of normal excitation rhythm. Experimental validation is provided by injecting the designed channel current for arrhythmia termination in human atrial myocytes using dynamic clamp. |
| first_indexed | 2024-04-12T02:44:11Z |
| format | Article |
| id | doaj.art-44d902c8f22d48b8a4feeb29a17f4531 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T02:44:11Z |
| publishDate | 2020-06-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-44d902c8f22d48b8a4feeb29a17f45312022-12-22T03:51:15ZengeLife Sciences Publications LtdeLife2050-084X2020-06-01910.7554/eLife.55921Self-restoration of cardiac excitation rhythm by anti-arrhythmic ion channel gatingRupamanjari Majumder0https://orcid.org/0000-0002-3851-9225Tim De Coster1https://orcid.org/0000-0002-4942-9866Nina Kudryashova2Arie O Verkerk3https://orcid.org/0000-0003-2140-834XIvan V Kazbanov4Balázs Ördög5Niels Harlaar6Ronald Wilders7https://orcid.org/0000-0002-1340-0869Antoine AF de Vries8Dirk L Ypey9Alexander V Panfilov10Daniël A Pijnappels11https://orcid.org/0000-0001-6731-4125Laboratory of Experimental Cardiology, Department of Cardiology, Leiden University Medical Center, Leiden, NetherlandsLaboratory of Experimental Cardiology, Department of Cardiology, Leiden University Medical Center, Leiden, Netherlands; Department of Physics and Astronomy, Ghent University, Ghent, Belgium; Department of Cardiovascular Sciences, KU Leuven, Leuven, BelgiumLaboratory of Experimental Cardiology, Department of Cardiology, Leiden University Medical Center, Leiden, Netherlands; Department of Physics and Astronomy, Ghent University, Ghent, BelgiumDepartment of Medical Biology, Amsterdam UMC, Amsterdam, Netherlands; Department of Experimental Cardiology, Amsterdam UMC, Amsterdam, NetherlandsDepartment of Physics and Astronomy, Ghent University, Ghent, BelgiumLaboratory of Experimental Cardiology, Department of Cardiology, Leiden University Medical Center, Leiden, NetherlandsLaboratory of Experimental Cardiology, Department of Cardiology, Leiden University Medical Center, Leiden, NetherlandsDepartment of Medical Biology, Amsterdam UMC, Amsterdam, NetherlandsLaboratory of Experimental Cardiology, Department of Cardiology, Leiden University Medical Center, Leiden, NetherlandsLaboratory of Experimental Cardiology, Department of Cardiology, Leiden University Medical Center, Leiden, NetherlandsLaboratory of Experimental Cardiology, Department of Cardiology, Leiden University Medical Center, Leiden, Netherlands; Department of Physics and Astronomy, Ghent University, Ghent, Belgium; Laboratory of Computational Biology and Medicine, Ural Federal University, Ekaterinburg, Russian FederationLaboratory of Experimental Cardiology, Department of Cardiology, Leiden University Medical Center, Leiden, NetherlandsHomeostatic regulation protects organisms against hazardous physiological changes. However, such regulation is limited in certain organs and associated biological processes. For example, the heart fails to self-restore its normal electrical activity once disturbed, as with sustained arrhythmias. Here we present proof-of-concept of a biological self-restoring system that allows automatic detection and correction of such abnormal excitation rhythms. For the heart, its realization involves the integration of ion channels with newly designed gating properties into cardiomyocytes. This allows cardiac tissue to i) discriminate between normal rhythm and arrhythmia based on frequency-dependent gating and ii) generate an ionic current for termination of the detected arrhythmia. We show in silico, that for both human atrial and ventricular arrhythmias, activation of these channels leads to rapid and repeated restoration of normal excitation rhythm. Experimental validation is provided by injecting the designed channel current for arrhythmia termination in human atrial myocytes using dynamic clamp.https://elifesciences.org/articles/55921rhythm disturbancesdefibrillationion channelsgating propertiescomputer modellingdynamic patch clamp |
| spellingShingle | Rupamanjari Majumder Tim De Coster Nina Kudryashova Arie O Verkerk Ivan V Kazbanov Balázs Ördög Niels Harlaar Ronald Wilders Antoine AF de Vries Dirk L Ypey Alexander V Panfilov Daniël A Pijnappels Self-restoration of cardiac excitation rhythm by anti-arrhythmic ion channel gating eLife rhythm disturbances defibrillation ion channels gating properties computer modelling dynamic patch clamp |
| title | Self-restoration of cardiac excitation rhythm by anti-arrhythmic ion channel gating |
| title_full | Self-restoration of cardiac excitation rhythm by anti-arrhythmic ion channel gating |
| title_fullStr | Self-restoration of cardiac excitation rhythm by anti-arrhythmic ion channel gating |
| title_full_unstemmed | Self-restoration of cardiac excitation rhythm by anti-arrhythmic ion channel gating |
| title_short | Self-restoration of cardiac excitation rhythm by anti-arrhythmic ion channel gating |
| title_sort | self restoration of cardiac excitation rhythm by anti arrhythmic ion channel gating |
| topic | rhythm disturbances defibrillation ion channels gating properties computer modelling dynamic patch clamp |
| url | https://elifesciences.org/articles/55921 |
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