A Compartmentalized Mathematical Model of Mouse Atrial Myocytes.

Various experimental mouse models are extensively used to research human diseases including atrial fibrillation, the most common cardiac rhythm disorder. Despite this, there are no comprehensive mathematical models that describe the complex behavior of the action potential and [Ca2+ ]i transients in mouse atrial myocytes. Here, we develop a novel compartmentalized mathematical model of mouse atrial myocytes which combines the action potential, [Ca2+ ]i dynamics, and β-adrenergic signaling cascade for a subpopulation of right atrial myocytes with developed transverse-axial tubule system. The model consists of three compartments related to β-adrenergic signaling (caveolae, extracaveolae, and cytosol) and employs local control of Ca2+ -release. It also simulates ionic mechanisms of action potential generation, describes atrial-specific Ca2+ handling as well as frequency dependences of the action potential and [Ca2+ ]i transients. The model showed that the T-type Ca2+ current significantly affects the later stage of the action potential with little effect on [Ca2+ ]i transients. The block of the small-conductance Ca2+ -activated K+ current leads to a prolongation of the action potential at high intracellular Ca2+ . Simulation results obtained from the atrial model cells were compared to those from ventricular myocytes. The developed model represents a useful tool to study complex electrical properties in the mouse atria and could be applied to enhance the understanding of atrial physiology and arrhythmogenesis.