Self-similar action potential cycle-to-cycle variability of Ca2+ and current oscillators in cardiac pacemaker cells

Published: Sept. 2, 2020, 9:01 a.m.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.09.01.277756v1?rss=1 Authors: Yang, D., Lyashkov, A. E., Morrell, C. H., Zahanich, I., Yaniv, Y., Vinogradova, T. M., Ziman, B. D., Maltsev, V. A., Lakatta, E. G. Abstract: Variability of heart pacemaker cell action potential (AP) firing intervals (APFI) means that pacemaker mechanisms do not achieve equilibrium during AP firing. We tested whether mechanisms that underlie APFI, in rabbit sinoatrial cells are self-similar within and across the physiologic range of APFIs effected by autonomic receptor stimulation. Principal Component Analyses demonstrated that means and variabilities of APFIs and local Calcium releases kinetics, of AP induced Calcium-transient decay times, of diastolic membrane depolarization rates, of AP repolarization times, of simulated ion current amplitudes, are self-similar across the broad range of APFIs (264 to 786 ms). Further, distributions of both mean APFIs and mean Calcium Variability of heart pacemaker cell action potential (AP) firing intervals (APFI) means that pacemaker mechanisms do not achieve equilibrium during AP firing. We tested whether mechanisms that underlie APFI, in rabbit sinoatrial cells are self-similar within and across the physiologic range of APFIs effected by autonomic receptor stimulation. Principal Component Analyses demonstrated that means and variabilities of APFIs and local Calcium releases kinetics, of AP induced Calcium-transient decay times, of diastolic membrane depolarization rates, of AP repolarization times, of simulated ion current amplitudes, are self-similar across the broad range of APFIs (264 to 786 ms). Further, distributions of both mean APFIs and mean Calcium and membrane potential dependent coupled-clock function kinetics manifested similar power law behaviors across the physiologic range of mean APFIs. Thus, self-similar variability of clock functions intrinsic to heart pacemaker cells determines both the mean APFI and its interval variability, and vice versa. and membrane potential dependent coupled-clock function kinetics manifested similar power law behaviors across the physiologic range of mean APFIs. Thus, self-similar variability of clock functions intrinsic to heart pacemaker cells determines both the mean APFI and its interval variability, and vice versa. Copy rights belong to original authors. Visit the link for more info