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|Self-restoration of cardiac excitation rhythm by anti-arrhythmic ion channel gating
De Coster, T.
Verkerk, A. O.
Kazbanov, I. V.
de Vries, A. A. F.
Ypey, D. L.
Panfilov, A. V.
Pijnappels, D. A.
|eLife Sciences Publications Ltd
|Self-restoration of cardiac excitation rhythm by anti-arrhythmic ion channel gating / R. Majumder, T. De Coster, N. Kudryashova, et al. — DOI 10.7554/eLife.55921 // eLife. — 2020. — Vol. 9. — P. 1-23. — e55921.
|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. © Majumder et al.
VOLTAGE DEPENDENT ANION CHANNEL
ATRIOVENTRICULAR NODAL REENTRY TACHYCARDIA
CARDIAC GATED IMAGING
CARDIAC MUSCLE CELL
PATCH CLAMP TECHNIQUE
ION CHANNEL GATING
REPRODUCIBILITY OF RESULTS
|This study was supported by The European Research Council (ERC Starting grant 716509) to DAP. Additional support was provided by the Netherlands Organisation for Scientific Research (NWO Vidi grant 91714336) to DAP, and by Ammodo (to DAP and AAFdV). The line of conditionally immortalised human atrial myocytes used in this study was made with financial support of the research programme More Knowledge with Fewer Animals (MKMD) with project number 114022503 (to AAFdV), which is (partly) financed by the Netherlands Organisation for Health Research and Development (ZonMw) and the Dutch Society for the Replacement of Animal Testing (dsRAT), and of the Leiden Regenerative Medicine Platform Holding (LRMPH project 8212/41235 to AAFdeV). We would like to thank Marie-José Goumans and Tessa van Herwaarden for their involvement in human tissue handling, Prof. Gunnar Seemann for helping with the atrial modeling, and Prof. Leon Glass and Alexander S Teplenin for useful discussions.
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|Научные публикации, проиндексированные в SCOPUS и WoS CC
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