Mechanisms of sinoatrial pacemaker synchronization: a new hypothesis

A model of electrically coupled sinus node cells was used to investigate pacemaker coordination and conduction. Individual cells were simulated using differential equations describing transmembrane ionic currents. Intrinsic cycle lengths (periods) were adjusted by applying constant depolarizing or hyperpolarizing bias current, and cells were coupled through ohmic resistances to form two-dimensional arrays. Activation maps of 81-225 coupled cells showed an apparent wavefront conducting from a leading pacemaker region to the rest of the matrix even though the pattern actually resulted from mutual entrainment of all spontaneously beating cells. Apparent conduction time increased with increasing intercellular resistance. Appropriate selection of pacemaker cycle lengths and intercellular resistances permitted the accurate simulation of the activation sequence seen experimentally for the rabbit sinus node. Furthermore, a simulated acetylcholine pulse applied to a randomly selected 20% of the cells in this model produced a pacemaker shift that lasted several beats. These results support the hypothesis that sinus node synchronization occurs through a "democratic" process resulting from the phase-dependent interactions of thousands of pacemakers.