We have just published our paper entitled "Self-restoration of cardiac excitation rhythm by anti-arrhythmic ion channel gating" in eLife.
Rupa, Tim and Nina et al. show in computer simulations that incorporation of an engineered ion channel in the virtual human heart allows the creation of a Biologically-Integrated Cardiac Defibrillator (BioICD), thereby enabling to heart itself to automatically detect and termination arrhythmias, ranging from atrial to ventricular fibrillation. Next, we apply dynamic clamp to cultured human atrial cardiomyocytes to study and confirm the anti-arrhythmic effects of the BioICD current.
This study is part of our endeavor to enable the heart to act as defibrillator through genetic modification, thereby replacing metal, wires, software and traumatizing electric shocks by a novel biological feedback system.
Thank you ERC (Starting Grant 716509) for the support.
Please find the abstract below:
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.
