Simulating cardiac sinus and atrial network dynamics on the connection machine

Computational methods for simulating biophysically detailed, large-scale models of mammalian cardiac sinus and atrial networks on the massively parallel Connection Machine CM-2, and techniques for visualization of simulation data, are presented. Individual cells are modeled using the formulations of Noble et al. Models incorporate properties of voltage-dependent membrane currents, ion pumps and exchangers, and internal calcium sequestering and release mechanisms. Network models are used to investigate factors determining the site of generation and direction of propagation of the pacemaker potential. Models of the isolated sinus node are used to show that very few gap junction channels are required to support frequency entrainment. When cell membrane properties in the isolated sinus node models are modified to reproduce regional differences in oscillation properties, as described by the data of Kodama and Boyett, an excitatory wave is generated in the node periphery which propagates towards the node center. This agrees with activation patterns measured in the isolated sinus node by Kirchoff. When the model sinus node is surrounded by a region of atrial cells, the site of pacemaker potential generation is shifted away from the periphery towards the node center. This is in agreement with activation patterns measured by Kirchoff in the intact sinus node of the rabbit heart, and demonstrates the importance of sinus node boundary conditions on shaping the site of generation and direction of propagation of the pacemaker potential.