Calcium waves initiating from the anomalous subdiffusive calcium sparks

Area of Science:

• Cardiovascular Physiology
• Biophysics
• Computational Biology

Background:

• Calcium (Ca(2+)) waves are crucial for cardiac myocyte excitation-contraction coupling.
• Understanding Ca(2+) wave propagation is essential for diagnosing and treating cardiac arrhythmias.
• Previous models often rely on Fick's law, which may not fully capture anomalous diffusion phenomena.

Purpose of the Study:

• To investigate Ca(2+) wave propagation in cardiac myocytes.
• To perform sensitivity analysis on physiological parameters influencing Ca(2+) waves.
• To develop and validate a mathematical model based on anomalous subdiffusion of Ca(2+) sparks.

Main Methods:

• Developed a mathematical model incorporating anomalous subdiffusion of Ca(2+) sparks.
• Included parameters such as current through Ca(2+) release units (CRU; ICRU), CRU open duration (Topen), Ca(2+) sensitivity (K), CRU spatial separation (lx, ly), and diffusion coefficients (Dx, Dy).
• Validated model outputs against experimental measurements using confocal microscopy.

Main Results:

• The model accurately reproduced experimental Ca(2+) wave dynamics.
• Current through CRU (ICRU) had a more significant impact on Ca(2+) wave dynamics than CRU open duration (Topen).
• Transverse CRU separation (ly) significantly affected wave amplitude, while longitudinal separation (lx) significantly impacted longitudinal velocity. Ca(2+) sensitivity (K) showed negligible effects.

Conclusions:

• The proposed model, based on anomalous subdiffusion, provides a more accurate characterization of Ca(2+) waves than models based on Fick's law.
• Physiological parameters, particularly CRU current and spatial arrangement, play critical roles in modulating Ca(2+) wave propagation.
• The findings offer insights into the spatio-temporal mechanisms governing Ca(2+) dynamics in cardiac myocytes.