Interbeat Interval Modulation in the Sinoatrial Node as a Result of Membrane Current Stochasticity-A Theoretical and Numerical Study

摘要

A single isolated sinoatrial pacemaker cell presents intrinsic interbeat interval (IBI) variability that is believed to result from the stochastic characteristics of the opening and closing processes of membrane ion channels. To our knowledge, a novel mathematical framework was developed in this work to address the effect of current fluctuations on the IBIs of sinoatrial pacemaker cells. Using statistical modeling and employing the Fokker-Planck formalism, our mathematical analysis suggests that increased stochastic current fluctuation variance linearly increases the slope of phase-4 depolarization, hence the rate of activations. Single-cell and two-dimensional computerized numerical modeling of the sinoatrial node was conducted to validate the theoretical predictions using established ionic kinetics of the rabbit pacemaker and atrial cells. Our models also provide, to our knowledge, a novel complementary or alternative explanation to recent experimental observations showing a strong reduction in the mean IBI of Cx30 deficient mice in comparison to wild-types, not fully explicable by the effects of intercellular decoupling.