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BioMed Research International
Volume 2013 (2013), Article ID 565431, 15 pages
http://dx.doi.org/10.1155/2013/565431
Research Article

Sensitivity of Rabbit Ventricular Action Potential and Ca2+ Dynamics to Small Variations in Membrane Currents and Ion Diffusion Coefficients

1Department of Bioengineering, PFBH 241, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0412, USA
2Faculty of Information Technology, Monash University, Clayton, VIC 3800, Australia

Received 28 April 2013; Accepted 19 August 2013

Academic Editor: Jeffrey J. Saucerman

Copyright © 2013 Yuan Hung Lo et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Little is known about how small variations in ionic currents and and diffusion coefficients impact action potential and dynamics in rabbit ventricular myocytes. We applied sensitivity analysis to quantify the sensitivity of Shannon et al. model (Biophys. J., 2004) to 5%–10% changes in currents conductance, channels distribution, and ion diffusion in rabbit ventricular cells. We found that action potential duration and peaks are highly sensitive to 10% increase in L-type current; moderately influenced by 10% increase in - exchanger, - pump, rapid delayed and slow transient outward currents, and background current; insensitive to 10% increases in all other ionic currents and sarcoplasmic reticulum fluxes. Cell electrical activity is strongly affected by 5% shift of L-type channels and - exchanger in between junctional and submembrane spaces while -activated -channel redistribution has the modest effect. Small changes in submembrane and cytosolic diffusion coefficients for , but not in transfer, may alter notably myocyte contraction. Our studies highlight the need for more precise measurements and further extending and testing of the Shannon et al. model. Our results demonstrate usefulness of sensitivity analysis to identify specific knowledge gaps and controversies related to ventricular cell electrophysiology and signaling.