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Impaired Sarcoplasmic Reticulum Calcium Uptake and Release Promote Electromechanically and Spatially Discordant Alternans: A Computational Study.

Weinberg SH - Clin Med Insights Cardiol (2016)

Bottom Line: Cardiac electrical dynamics are governed by cellular-level properties, such as action potential duration (APD) restitution and intracellular calcium (Ca) handling, and tissue-level properties, including conduction velocity restitution and cell-cell coupling.Irregular dynamics at the cellular level can lead to instabilities in cardiac tissue, including alternans, a beat-to-beat alternation in the action potential and/or the intracellular Ca transient.We find that an intermediate SR Ca uptake rate and larger SR Ca release resulted in the widest range of stimulus periods that promoted alternans.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical Engineering, Virginia Commonwealth University, Richmond, VA, USA.

ABSTRACT
Cardiac electrical dynamics are governed by cellular-level properties, such as action potential duration (APD) restitution and intracellular calcium (Ca) handling, and tissue-level properties, including conduction velocity restitution and cell-cell coupling. Irregular dynamics at the cellular level can lead to instabilities in cardiac tissue, including alternans, a beat-to-beat alternation in the action potential and/or the intracellular Ca transient. In this study, we incorporate a detailed single cell coupled map model of Ca cycling and bidirectional APD-Ca coupling into a spatially extended tissue model to investigate the influence of sarcoplasmic reticulum (SR) Ca uptake and release properties on alternans and conduction block. We find that an intermediate SR Ca uptake rate and larger SR Ca release resulted in the widest range of stimulus periods that promoted alternans. However, both reduced SR Ca uptake and release promote arrhythmogenic spatially and electromechanically discordant alternans, suggesting a complex interaction between SR Ca handling and alternans characteristics at the cellular and tissue level.

No MeSH data available.


Related in: MedlinePlus

Single cell and one-dimensional cable simulations. (A, top) Illustration of the APD an, DI dn, and IBI tn; (middle) peak intracellular Ca  at the end of each beat (cn), SR Ca release (rn); (bottom) and SR Ca load at the end of each beat (ln). (B) Illustration of action potential wavefronts (solid) and wavebacks (dashed), propagating along a cable, denoting APD, DI, and IBI as an(x), dn(x), and tn(x), respectively, as functions of space x.
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f1-cmc-suppl.1-2016-001: Single cell and one-dimensional cable simulations. (A, top) Illustration of the APD an, DI dn, and IBI tn; (middle) peak intracellular Ca at the end of each beat (cn), SR Ca release (rn); (bottom) and SR Ca load at the end of each beat (ln). (B) Illustration of action potential wavefronts (solid) and wavebacks (dashed), propagating along a cable, denoting APD, DI, and IBI as an(x), dn(x), and tn(x), respectively, as functions of space x.

Mentions: In this section, we describe in brief the single myocyte-coupled map, incorporating excitation–contraction coupling, previously described by Qu et al.25 and illustrated in Figure 1A. As mentioned in the “Introduction” section, APD is often assumed to be a function of the preceding DI via APD restitution.16 In this model, APD is governed by both voltage-dependent recovery kinetics and Ca-dependent processes, ie,an+1=f(dn)+γcn+1pan+1,=11−γcn+1pf(dn),(1)where an+1 is the APD of the (n + 1)th beat, is the peak intracellular Ca on the (n + 1)th beat, γ governs Ca–APD coupling, f(dn) is the APD restitution function (Eq. A1), dn is the DI of the nth beat, and an and dn are related by tn = an + dn, where tn is the interbeat interval (IBI) of the nth beat.


Impaired Sarcoplasmic Reticulum Calcium Uptake and Release Promote Electromechanically and Spatially Discordant Alternans: A Computational Study.

Weinberg SH - Clin Med Insights Cardiol (2016)

Single cell and one-dimensional cable simulations. (A, top) Illustration of the APD an, DI dn, and IBI tn; (middle) peak intracellular Ca  at the end of each beat (cn), SR Ca release (rn); (bottom) and SR Ca load at the end of each beat (ln). (B) Illustration of action potential wavefronts (solid) and wavebacks (dashed), propagating along a cable, denoting APD, DI, and IBI as an(x), dn(x), and tn(x), respectively, as functions of space x.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4920205&req=5

f1-cmc-suppl.1-2016-001: Single cell and one-dimensional cable simulations. (A, top) Illustration of the APD an, DI dn, and IBI tn; (middle) peak intracellular Ca at the end of each beat (cn), SR Ca release (rn); (bottom) and SR Ca load at the end of each beat (ln). (B) Illustration of action potential wavefronts (solid) and wavebacks (dashed), propagating along a cable, denoting APD, DI, and IBI as an(x), dn(x), and tn(x), respectively, as functions of space x.
Mentions: In this section, we describe in brief the single myocyte-coupled map, incorporating excitation–contraction coupling, previously described by Qu et al.25 and illustrated in Figure 1A. As mentioned in the “Introduction” section, APD is often assumed to be a function of the preceding DI via APD restitution.16 In this model, APD is governed by both voltage-dependent recovery kinetics and Ca-dependent processes, ie,an+1=f(dn)+γcn+1pan+1,=11−γcn+1pf(dn),(1)where an+1 is the APD of the (n + 1)th beat, is the peak intracellular Ca on the (n + 1)th beat, γ governs Ca–APD coupling, f(dn) is the APD restitution function (Eq. A1), dn is the DI of the nth beat, and an and dn are related by tn = an + dn, where tn is the interbeat interval (IBI) of the nth beat.

Bottom Line: Cardiac electrical dynamics are governed by cellular-level properties, such as action potential duration (APD) restitution and intracellular calcium (Ca) handling, and tissue-level properties, including conduction velocity restitution and cell-cell coupling.Irregular dynamics at the cellular level can lead to instabilities in cardiac tissue, including alternans, a beat-to-beat alternation in the action potential and/or the intracellular Ca transient.We find that an intermediate SR Ca uptake rate and larger SR Ca release resulted in the widest range of stimulus periods that promoted alternans.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical Engineering, Virginia Commonwealth University, Richmond, VA, USA.

ABSTRACT
Cardiac electrical dynamics are governed by cellular-level properties, such as action potential duration (APD) restitution and intracellular calcium (Ca) handling, and tissue-level properties, including conduction velocity restitution and cell-cell coupling. Irregular dynamics at the cellular level can lead to instabilities in cardiac tissue, including alternans, a beat-to-beat alternation in the action potential and/or the intracellular Ca transient. In this study, we incorporate a detailed single cell coupled map model of Ca cycling and bidirectional APD-Ca coupling into a spatially extended tissue model to investigate the influence of sarcoplasmic reticulum (SR) Ca uptake and release properties on alternans and conduction block. We find that an intermediate SR Ca uptake rate and larger SR Ca release resulted in the widest range of stimulus periods that promoted alternans. However, both reduced SR Ca uptake and release promote arrhythmogenic spatially and electromechanically discordant alternans, suggesting a complex interaction between SR Ca handling and alternans characteristics at the cellular and tissue level.

No MeSH data available.


Related in: MedlinePlus