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

Abstract

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 G c < 1 pS; (2) primarily quasiperiodic oscillation for 1 ⩽ G c < 116 pS; (3) windows of periodic behavior which undergo period doubling bifurcation to chaos for 116 ⩽ G c < 212 pS; (4) frequency entrainment for G c ⩾ 212 pS; (5) waveform entrainment for G c ⩾ 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.