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Articles in PresS, published online ahead of print November 29, 2001
Am J Physiol Heart Circ Physiol, 10.1152/ajpheart.00489.2001
Submitted on June 4, 2001
Accepted on November 20, 2001
1 Research Center, Montreal Heart Institute, Montreal, Quebec, Canada
* To whom correspondence should be addressed. E-mail: nattel{at}icm.umontreal.ca.
Ionically-based cardiac action potential (AP) models are based on equations with singular Jacobians and display time-dependent AP and ionic changes (transients), which may be due to this mathematical limitation. The present study evaluated transients during long-term simulated activity in a mathematical model of the canine atrial AP. Stimulus current assignment to a specific ionic species contributed to stability. Ionic concentrations were least disturbed with K+-stimulus current. All parameters stabilized within 6 to 7 h. Inward-rectifier, Na+/Ca2+-exchanger, L-type Ca2+, and Na+/Cl- co-transporter currents made the greatest contributions to stabilization of intracellular [K+], [Na+], [Ca2+] and [Cl-]respectively. Time-dependent AP-shortening was largely due to outward shift of Na+/Ca2+-exchange related to Na+i accumulation. AP duration (APD) reached steady state after ~40 min. AP transients also occurred in canine atrial preparations, with APD decreasing by ~10 ms over 35 min, compared to ~27 ms in the model. We conclude that model APD and ionic transients stabilize with appropriate stimulus current assignment and that the mathematical limitation of equation singularity does not preclude meaningful longterm simulations. The model agrees qualitatively with experimental observations, but quantitative discrepancies highlight limitations of long-term model simulations.
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