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Sensitivity of rabbit ventricular action potential and Ca²⁺ dynamics to small variations in membrane currents and ion diffusion coefficients.

Lo YH, Peachey T, Abramson D, McCulloch A, Michailova A - Biomed Res Int (2013)

Bottom Line: We applied sensitivity analysis to quantify the sensitivity of Shannon et al. model (Biophys.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 Ca²⁺ signaling.

View Article: PubMed Central - PubMed

Affiliation: Department of Bioengineering, PFBH 241, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0412, USA.

ABSTRACT
Little is known about how small variations in ionic currents and Ca²⁺ and Na⁺ diffusion coefficients impact action potential and Ca²⁺ 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 Ca²⁺ peaks are highly sensitive to 10% increase in L-type Ca²⁺ current; moderately influenced by 10% increase in Na⁺-Ca²⁺ exchanger, Na⁺-K⁺ pump, rapid delayed and slow transient outward K⁺ currents, and Cl⁻ background current; insensitive to 10% increases in all other ionic currents and sarcoplasmic reticulum Ca²⁺ fluxes. Cell electrical activity is strongly affected by 5% shift of L-type Ca²⁺ channels and Na⁺-Ca²⁺ exchanger in between junctional and submembrane spaces while Ca²⁺-activated Cl⁻-channel redistribution has the modest effect. Small changes in submembrane and cytosolic diffusion coefficients for Ca²⁺, but not in Na⁺ 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 Ca²⁺ signaling.

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Schematic diagram illustrating the four subcellular compartments, electrophysiology, and Ca2+ dynamics in the Shannon et al. model in rabbit ventricular myocytes [1]. See Glossary and Tables 1–3 for the notations of the parameters used throughout the study.
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fig1: Schematic diagram illustrating the four subcellular compartments, electrophysiology, and Ca2+ dynamics in the Shannon et al. model in rabbit ventricular myocytes [1]. See Glossary and Tables 1–3 for the notations of the parameters used throughout the study.

Mentions: A diagram describing the arrangement of subcellular compartments, ionic currents and pumps, and intracellular Ca2+ fluxes included in the Shannon et al. electrophysiological model is shown in Figure 1.


Sensitivity of rabbit ventricular action potential and Ca²⁺ dynamics to small variations in membrane currents and ion diffusion coefficients.

Lo YH, Peachey T, Abramson D, McCulloch A, Michailova A - Biomed Res Int (2013)

Schematic diagram illustrating the four subcellular compartments, electrophysiology, and Ca2+ dynamics in the Shannon et al. model in rabbit ventricular myocytes [1]. See Glossary and Tables 1–3 for the notations of the parameters used throughout the study.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3814049&req=5

fig1: Schematic diagram illustrating the four subcellular compartments, electrophysiology, and Ca2+ dynamics in the Shannon et al. model in rabbit ventricular myocytes [1]. See Glossary and Tables 1–3 for the notations of the parameters used throughout the study.
Mentions: A diagram describing the arrangement of subcellular compartments, ionic currents and pumps, and intracellular Ca2+ fluxes included in the Shannon et al. electrophysiological model is shown in Figure 1.

Bottom Line: We applied sensitivity analysis to quantify the sensitivity of Shannon et al. model (Biophys.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 Ca²⁺ signaling.

View Article: PubMed Central - PubMed

Affiliation: Department of Bioengineering, PFBH 241, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0412, USA.

ABSTRACT
Little is known about how small variations in ionic currents and Ca²⁺ and Na⁺ diffusion coefficients impact action potential and Ca²⁺ 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 Ca²⁺ peaks are highly sensitive to 10% increase in L-type Ca²⁺ current; moderately influenced by 10% increase in Na⁺-Ca²⁺ exchanger, Na⁺-K⁺ pump, rapid delayed and slow transient outward K⁺ currents, and Cl⁻ background current; insensitive to 10% increases in all other ionic currents and sarcoplasmic reticulum Ca²⁺ fluxes. Cell electrical activity is strongly affected by 5% shift of L-type Ca²⁺ channels and Na⁺-Ca²⁺ exchanger in between junctional and submembrane spaces while Ca²⁺-activated Cl⁻-channel redistribution has the modest effect. Small changes in submembrane and cytosolic diffusion coefficients for Ca²⁺, but not in Na⁺ 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 Ca²⁺ signaling.

Show MeSH
Related in: MedlinePlus