Rabbit sino-atrial node modeling: From single cell to tissue structure

Multicellular models of atrial structure and function have recently started to emerge, but still lack the level of anatomical and electrophysiological detail of their ventricular counterparts. This discrepancy needs to be addressed in order to approach whole heart modeling, including implementation of viable models of intrinsic cardiac pacemaking in the sino-atrial node (SAN). We addressed this issue by developing 1D, 2D and, more recently, 3D SAN-atrial models. Electrophysiological descriptions are based on published single cell models of rabbit SAN and atrial myocytes. Electrotonic interaction is via gap junctions, which are modeled based on experimental data from isolated rabbit SAN and atrial cell pairs. In 1D simulations, intercellular conductivities need to be scaled up beyond the levels observed in isolated cell pairs to achieve normal sinus rhythm. This is not required in models of higher spatial dimensionality. Implementation of detailed anatomical information in 2D SAN models allows reproduction of the spread of excitation from the central SAN towards the Crista terminalis, rather than the atrial septum. This level of structural detail will also be required in 3D models, as otherwise non-physiological conduction patterns are observed. Thus, dimensionality and cell distribution information are critical for normal origin and spread of SAN excitation.