Variability of pacemaker rhythm in a detailed model of cardiac sinoatrial node cells

The sinoatrial node (cardiac pacemaker) cell spontaneously generates periodic electrical signals (action potentials), and the action potential generation is deeply related to various ion channels in its cell membrane. The abnormalities of ion channels cause serious sinus arrhythmia, and such diseases are usually treated by applying drugs which have effects on ion channels. This paper uses the Zhang model of sinoatrial node cells to investigate the relation between pacemaker rhythm (frequency of action potential generation) and ion channels. The Zhang model is described by the Hodgkin-Huxley-type nonlinear ordinary differential equations, and its parameter values depend on the region (periphery or center) of the sinoatrial node. We analyze the bifurcation structure of the Zhang model, and examine the variabilities of pacemaker rhythm and its sensitivities on conductance changes of ion channels for both periphery and center cells. Moreover, these results are compared to the previous results of another sinoatrial node cell model (Yanagihara-Noma-Irisawa model). The above results are expected to be useful in the treatment of sinus arrhythmia.