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1 School of Biomedical Sciences, University of Leeds, Leeds LS2 9JT, United Kingdom; 2 Departments of Circulation and Humoral Regulation, Research Institute of Environmental Medicine, Nagoya University, Nagoya 464-01, Japan; and 3 Institute for Mathematics and Its Application, University of Minnesota, Minneapolis, Minnesota 55455
Mathematical models of the action potential in the periphery and center of the rabbit sinoatrial (SA) node have been developed on the basis of published experimental data. Simulated action potentials are consistent with those recorded experimentally: the model-generated peripheral action potential has a more negative takeoff potential, faster upstroke, more positive peak value, prominent phase 1 repolarization, greater amplitude, shorter duration, and more negative maximum diastolic potential than the model-generated central action potential. In addition, the model peripheral cell shows faster pacemaking. The models behave qualitatively the same as tissue from the periphery and center of the SA node in response to block of tetrodotoxin-sensitive Na+ current, L- and T-type Ca2+ currents, 4-aminopyridine-sensitive transient outward current, rapid and slow delayed rectifying K+ currents, and hyperpolarization-activated current. A one-dimensional model of a string of SA node tissue, incorporating regional heterogeneity, coupled to a string of atrial tissue has been constructed to simulate the behavior of the intact SA node. In the one-dimensional model, the spontaneous action potential initiated in the center propagates to the periphery at ~0.06 m/s and then into the atrial muscle at 0.62 m/s.
heart; pacemaking; regional differences; computer modeling
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