What question did this study set out to answer?

To determine how electrotonic gap junction coupling between fibroblasts and myocytes alters action potential dynamics and intracellular calcium cycling at cellular and tissue scales.

May 30, 2009AJP Heart and Circulatory PhysiologyOpen Access

Cardiac alternans induced by fibroblast-myocyte coupling: mechanistic insights from computational models

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Why the study?

Does fibroblast-myocyte coupling alter action potential duration and promote cardiac alternans in simulated cardiac tissue?

Population

Simulated fibroblast-myocyte pairs and two-dimensional ventricular tissue models with random fibroblast…

Comparison

Fibroblast-myocyte coupling via gap junctions. vs Uncoupled myocytes or control conditions without…

Design

Preclinical

Authors

YXYuanfang XieGuangzhou University of Chinese Medicine AGAlan GarfinkelElectrophysiology JWJames N. WeissElectrophysiology

Discussion

Member takes

Implication

May promote alternans-mediated arrhythmias in fibrotic hearts; hypothesis-generating for clinical translation.

Key Points

To determine how electrotonic gap junction coupling between fibroblasts and myocytes alters action potential dynamics and intracellular calcium cycling at cellular and tissue scales.
Simulated electrotonic interactions within isolated fibroblast-myocyte pairs using computational action potential models.
Modeled two-dimensional cardiac tissue incorporating random fibroblast distributions to assess spatial dynamics and conduction velocity restitution.
Coupling generated a biphasic gap junction current consisting of an early transient outward pulse and a late background current, which either prolonged or shortened action potential duration depending on their balance.
Fibroblast coupling modulated voltage-driven action potential duration alternans, initiated a novel alternans mechanism at slow heart rates, and promoted intracellular calcium-driven alternans.
Heterogeneous fibroblast distribution and altered conduction velocity restitution promoted spatially discordant alternans across simulated two-dimensional cardiac tissue.

Structured PICO

Does fibroblast-myocyte coupling alter action potential duration and promote cardiac alternans in simulated cardiac tissue?

Population

Simulated fibroblast-myocyte pairs and two-dimensional ventricular tissue models with random fibroblast insertions, utilizing the Luo-Rudy phase I (LR1) model and a rabbit ventricular action potential model.

Intervention

Fibroblast-myocyte coupling via gap junctions (varying gap junction conductance, fibroblast membrane conductance, and resting potential).

Comparator

Uncoupled myocytes or control conditions without fibroblasts.

Outcome

Action potential duration (APD), APD alternans, intracellular calcium (Cai) cycling dynamics, and conduction velocity.surrogate

Fibroblast-myocyte coupling alters repolarization and calcium cycling alternans at cellular and tissue scales, providing a mechanistic basis for arrhythmogenesis in fibrotic cardiac tissue.

Limitations

Use of a phenomenological (passive) model for fibroblasts because exact properties of in vivo cardiac fibroblasts are still unknown.

Cite This Study

Xie et al. (2009) studied this question.

synapsesocial.com/papers/6a70a4c6f44fa9f079de521e https://doi.org/10.1152/ajpheart.00341.2009

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