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Assessment of Sarcoplasmic Reticulum Calcium Reserve and Intracellular Diastolic Calcium Removal in Isolated Ventricular Cardiomyocytes
Published on: September 18, 2017
Predicting local SR Ca(2+) dynamics during Ca(2+) wave propagation in ventricular myocytes
Hena R Ramay1, M Saleet Jafri, W Jonathan Lederer
1Pharmacology and Systems Therapeutics, Mount Sinai School of Medicine, New York, New York, USA.
Biophysical Journal
|June 2, 2010
Summary
Calcium wave propagation in cardiac cells depends on calcium diffusion within the sarcoplasmic reticulum (SR). Slow SR diffusion may facilitate wave propagation by allowing local calcium increases ahead of the wave.
Area of Science:
- Cardiovascular Physiology
- Cellular Biology
- Computational Biology
Background:
- Controversies exist regarding sarcoplasmic reticulum (SR) function in cardiac myocytes, specifically calcium (Ca2+) wave propagation and Ca2+ diffusion speed within the SR.
- Calcium waves initiate from local SR Ca2+ release events, triggering neighboring release channels (ryanodine receptors, RyRs).
- Lack of consensus on the Ca2+ diffusion constant in the SR (D(Ca,SR)) hinders understanding of its influence on wave propagation.
Purpose of the Study:
- To investigate the influence of SR Ca2+ diffusion dynamics on Ca2+ wave propagation.
- To explore how factors like D(Ca,SR), RyR cluster distance, and SR Ca2+ pump activity affect local SR Ca2+ changes during wave propagation.
Main Methods:
- Implementation of a computational model simulating cytosolic and SR Ca2+ concentrations during Ca2+ waves.
- Simulation of various conditions including different D(Ca,SR) values, RyR cluster distances, SR Ca2+ pump inhibition/stimulation, pump dependence on cytosolic Ca2+, and network-junctional SR transfer rates.
Main Results:
- D(Ca,SR) is identified as the primary determinant of how Ca2+ release from one RyR cluster affects nearby SR Ca2+ levels.
- Local increases in SR Ca2+ ahead of the wave can potentially facilitate wave propagation.
- This facilitation is contingent upon relatively slow SR Ca2+ diffusion.
Conclusions:
- Dynamic local changes in SR Ca2+ concentration are possible during SR Ca2+ release events.
- Slow SR Ca2+ diffusion plays a crucial role in modulating Ca2+ wave propagation.
- This study enhances the understanding of regulatory roles of dynamic Ca2+ changes within the SR.
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