Three distinct types of pacemaker cells in the sinoatrial node: computer simulations

Based on recent experimental data, the rapid and slow potassium currents (I_Kr and I_Ks, respectively) were incorporated into the rabbit sinoatrial node (SAN) model of Demir et al. (1994) in place of I_K. Using the modified model as a template, computational models of elongated spindle, spindle, and spider cells were then developed, which agree with data from isolated rabbit sinoatrial node cells of the three types (Verheijck et al. 1998). The biophysically detailed models are consistent with the known properties of rabbit SAN cells in terms of membrane current behavior, amplitudes, and ion concentrations In the intracellular and extracellular spaces. Modeled application of Cs⁺, which reduces both the hyperpolarization activated cation current (I_f) and I_Kr , on the three cell types yielded an increase in period of pacing (PP) by 14%, 23%, and 5.4% for spider, spindle, and elongated spindle cells, respectively. The modeled application of Ni²⁺, which reduces the low-threshold Ca²⁺ current, yielded an increase in the PP by 26%, 17%, and 4.3%, for spider, spindle, and elongated spindle cells, respectively. The simulated application of propofol, which reduces I_Kr, reduced the PP by 8.1%, 13%, and 25% in spider, spindle, and elongated spindle cells, respectively. The modeled application of E-4031 which is known to reduce I_Kr, abolished pacing in all three cell types. The models are based on physiological data, and demonstrate the proper behavior under drug applications. The underlying mechanisms which differentiate the cell types provide plausible mechanisms for cellular differences in the SAN tissue