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Updated: May 11, 2026
Measuring Fast Calcium Fluxes in Cardiomyocytes
Published on: November 29, 2011
The timing statistics of spontaneous calcium release in cardiac myocytes
Mesfin Asfaw1, Enric Alvarez-Lacalle, Yohannes Shiferaw
1Department of Physics and Astronomy, California State University Northridge, Northridge, California, United States of America.
Insights
This study models spontaneous calcium release (SCR) in cardiac cells to understand arrhythmia timing. It identifies conditions where SCR timing aligns with the cardiac cycle and synchronizes across cells, potentially causing triggered excitations.
Area of Science:
- Cardiology
- Biophysics
- Computational Biology
Background:
- Cardiac arrhythmias can originate from focal excitations disrupting normal heart rhythm.
- Subcellular calcium (Ca) waves released from the sarcoplasmic reticulum (SR) are implicated in initiating these excitations.
- The physiological determinants of excitation timing at subcellular and tissue levels remain unclear.
Purpose of the Study:
- To analyze the timing statistics of spontaneous calcium release (SCR) in a simplified cardiac myocyte model.
- To identify physiological factors governing SCR timing at subcellular and tissue scales.
- To investigate conditions leading to arrhythmogenic triggered excitations.
Main Methods:
- Application of analytic and numerical approaches to model cardiac myocyte function.
- Computation of the mean first passage time (MFPT) to spontaneous calcium release (SCR).
- Analysis of SCR synchronization across multiple cardiac cells using a quantitative measure.
Main Results:
- The mean first passage time (MFPT) to SCR shows algebraic or exponential dependence on system parameters.
- Conditions are identified for SCR timing to occur within the cardiac cycle duration.
- A quantitative measure reveals conditions for minimized cell-to-cell SCR timing variations.
Conclusions:
- SCR timing is critically dependent on specific physiological parameters.
- Synchronization of SCR across cardiac cells can lead to arrhythmogenic triggered excitations.
- Understanding SCR timing is crucial for elucidating mechanisms of cardiac arrhythmias.
Abstract:
A variety of cardiac arrhythmias are initiated by a focal excitation that disrupts the regular beating of the heart. In some cases it is known that these excitations are due to calcium (Ca) release from the sarcoplasmic reticulum (SR) via propagating subcellular Ca waves. However, it is not understood what are the physiological factors that determine the timing of these excitations at both the subcellular and tissue level. In this paper we apply analytic and numerical approaches to determine the timing statistics of spontaneous Ca release (SCR) in a simplified model of a cardiac myocyte. In particular, we compute the mean first passage time (MFPT) to SCR, in the case where SCR is initiated by spontaneous Ca sparks, and demonstrate that this quantity exhibits either an algebraic or exponential dependence on system parameters. Based on this analysis we identify the necessary requirements so that SCR occurs on a time scale comparable to the cardiac cycle. Finally, we study how SCR is synchronized across many cells in cardiac tissue, and identify a quantitative measure that determines the relative timing of SCR in an ensemble of cells. Using this approach we identify the physiological conditions so that cell-to-cell variations in the timing of SCR is small compared to the typical duration of an SCR event. We argue further that under these conditions inward currents due to SCR can summate and generate arrhythmogenic triggered excitations in cardiac tissue.
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