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Creating a Structurally Realistic Finite Element Geometric Model of a Cardiomyocyte to Study the Role of Cellular Architecture in Cardiomyocyte Systems Biology

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[Interaction of Membrane and Calcium Oscillators in Cardiac Pacemaker Cells: Mathematical Modeling].

A M Ryvkin, N M Zorin, A S Moskvin

|February 5, 2016

Summary

This study models cardiac pacemaker cells, integrating membrane and intracellular calcium oscillators. The model shows stable heartbeats despite calcium release variability, crucial for understanding cardiac rhythm.

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Area of Science:

Computational biology
Cardiac electrophysiology
Calcium signaling

Context:

Cardiac pacemaker cells generate heart rhythm through complex electrical and calcium signaling pathways.
The interplay between membrane potential oscillations and intracellular calcium dynamics is critical for stable pacemaking.
Stochasticity in calcium release mechanisms, particularly involving ryanodine receptors, poses a challenge to understanding normal heart function.

Purpose:

To develop an integrative computational model of cardiac pacemaker cell calcium dynamics.
To investigate the synergetic interaction between the "membrane clock" and the "Ca(2+)-clock" in pacemaker cells.
To analyze the impact of stochastic calcium release and ryanodine receptor sensitivity on action potential generation.

Summary:

An integrative model of cardiac pacemaker cell calcium dynamics is presented, incorporating coupled membrane and intracellular calcium oscillators.
The model features stochastic dynamics of calcium release units via the electron-conformational mechanism of ryanodine-sensitive calcium channels.
Stable action potential generation is demonstrated even with stochastic calcium dynamics, highlighting the robustness of the coupled oscillator system.

Impact:

Provides a mechanistic understanding of how coupled cellular oscillators ensure stable cardiac pacemaking.
Reveals the critical role of ryanodine receptor sensitivity in regulating calcium release and its impact on pacemaker function.
Offers a valuable computational tool for further research into cardiac arrhythmias and potential therapeutic targets.