Generation and propagation of normal and abnormal pacemaker activity in network models of cardiac sinus node and atrium

Effects of cell-to-cell coupling conductance on dynamics of sinus node cells are examined. Cell models are biophysically detailed, and are based on the kinetic equations developed by Noble et al. [Neuronal and Cellular Oscillators, edited by J. W. Jacklet, Marcel Deckker, New York (1989).] Resistively coupled cell pairs show five regimes of behavior as a function of coupling conductance: (1) independent oscillation for Gc < 1 pS; (2) primarily quasiperiodic oscillation for 1 Gc < 116 pS; (3) windows of periodic behavior which undergo period doubling bifurcation to chaos for 116 Gc < 212 pS; (4) frequency entrainment for Gc 212 pS; (5) waveform entrainment for Gc 50 nS. Thus, only 4–5 gap junction channels are required for frequency entrainment. This is shown to also be the case for large networks of sinus cells modeled on the Connection Machine CM-5. A biophysically detailed two-dimensional network model of the cardiac atrium has also been implemented on the CM-5 supercomputer. The model is used to study effects of spatially localized inhibition of the Na-K pump. Na overloading produced by pump inhibition can induce spontaneous, propagating ectopic beats within the network. At a cell-to-cell coupling value yielding a realistic plane wave conduction velocity of 60cms−1 pump inhibition in small regions of the network containing as few as 1000 cells can induce propagating ectopic beats.