Modeling Calcium Cycling in the Heart: Progress, Pitfalls, and Challenges

Area of Science:

• Cardiovascular Physiology
• Computational Biology
• Biophysics

Background:

• Intracellular calcium (Ca) cycling is crucial for cardiac excitation-contraction coupling and arrhythmogenesis.
• Cardiac myocytes feature calcium release units (CRUs) composed of ryanodine receptors (RyRs) that generate Ca sparks.
• A complex CRU network exhibits diverse spatiotemporal Ca dynamics, including sparks, waves, and oscillations.

Purpose of the Study:

• To review the progress in modeling cardiac Ca cycling dynamics across different scales.
• To analyze the advantages and disadvantages of various modeling approaches.
• To identify future challenges in modeling cardiac Ca cycling at the tissue level.

Main Methods:

• Review of existing literature on cardiac Ca cycling models.
• Analysis of models ranging from single RyRs to whole-tissue simulations.
• Discussion of computational approaches and their limitations.

Main Results:

• Models of varying temporal and spatial scales have been developed to study cardiac Ca dynamics.
• Significant challenges exist in accurately modeling the CRU network and tissue-scale Ca cycling.
• Current models offer insights but require further development for comprehensive understanding.

Conclusions:

• Modeling cardiac Ca cycling is complex due to intricate CRU networks and spatiotemporal dynamics.
• Further advancements are needed to bridge the gap between single-cell and tissue-level models.
• Improved models are essential for a deeper understanding of cardiac function and disease.