Self-restoration of cardiac excitation rhythm by anti-arrhythmic ion channel gating

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

Research output: Contribution to journalArticlepeer-review

Abstract

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.
Original languageEnglish
Article numbere55921
Number of pages23
JournaleLIFE
Volume9
Early online date8 Jun 2020
DOIs
Publication statusPublished - 25 Jun 2020

Keywords

  • rhythm disturbances
  • defibrillation
  • ion channels
  • gating properties
  • computer modelling
  • dynamic patch clamp

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