Computational modeling and numerical methods for spatiotemporal calcium cycling in ventricular myocytes

Area of Science:

• Computational biology
• Cardiac electrophysiology
• Biophysics

Background:

• Intracellular calcium (Ca) cycling in cardiac myocytes is crucial for heart function.
• This process involves complex interactions between organelles like the sarcoplasmic reticulum (SR) and mitochondria.
• Understanding these dynamics is key to addressing cardiac arrhythmias and heart failure.

Purpose of the Study:

• To develop a detailed mathematical model of intracellular Ca cycling in cardiac myocytes.
• To implement efficient numerical and computational methods for simulating these dynamics.
• To investigate phenomena such as Ca sparks, waves, and alternans.

Main Methods:

• A coupled Ca release unit (CRU) network model was developed, incorporating SR and myoplasm domains.
• Individual L-type Ca channels and ryanodine receptor channels were stochastically simulated using a modified Gillespie's method.
• Advanced numerical algorithms on GPUs were employed for fast, large-scale simulations of a myocyte with numerous CRUs.

Main Results:

• The model successfully simulated key intracellular Ca cycling dynamics, including Ca sparks, waves, and alternans.
• Simulations demonstrated the feasibility of modeling complex Ca dynamics within cardiac myocytes.
• A 1-second heart time simulation required approximately 10 minutes on a single NVIDIA Tesla C2050 GPU.

Conclusions:

• The developed mathematical model and computational approach provide a powerful tool for studying cardiac Ca cycling.
• This simulation framework can elucidate the mechanisms underlying normal and abnormal heart rhythms.
• The study highlights the potential of GPU-accelerated computing in advancing cardiovascular research.