Exploring Impaired SERCA Pump-Caused Alternation Occurrence in Ischemia.
Jiaqi Liu1, Xiaoye Zhao2, Yinglan Gong1,3
1Key Laboratory for Biomedical Engineering of Ministry of Education, Institute of Biomedical Engineering, Zhejiang University, Hangzhou 310027, China.
Computational and Mathematical Methods in Medicine
|December 13, 2019
Summary
Impaired sarcoplasmic reticulum (SR) calcium transport ATPase (SERCA) function causes calcium alternans. A new diastolic Ca ratio (Ca_nsr/Ca_cyt) threshold better predicts calcium alternans onset during ischemia.
Area of Science:
- Cardiovascular Physiology
- Cellular Electrophysiology
- Biophysics
Background:
- Impaired sarcoplasmic reticulum (SR) calcium transport ATPase (SERCA) function leads to calcium alternans and altered calcium release.
- Understanding the interplay between calcium release and uptake in inducing calcium alternans is crucial for elucidating arrhythmogenesis.
- Previous studies have not explored the direct calculation of calcium release properties in SERCA-impaired conditions leading to alternans.
Purpose of the Study:
- To investigate the mechanism of calcium alternans induced by impaired SERCA under ischemic conditions.
- To propose and validate a novel 'threshold' for calcium wave and calcium alternans onset.
- To assess the utility of this threshold in differentiating calcium alternans across various ischemic scenarios.
Main Methods:
- Induction of calcium alternans using an impaired SERCA pump model under simulated ischemic conditions.
- Calculation and analysis of calcium release properties, including recruitment and refractoriness.
- Measurement of diastolic network SR (NSR) Ca content (Ca_nsr) and cytoplasmic Ca content (Ca_cyt) at the onset of calcium alternans.
Main Results:
- Impaired SERCA function under ischemia induced calcium alternans, characterized by increased Ca2+ release recruitment and refractoriness, indicating triggered Ca waves.
- The ratio of diastolic Ca_nsr to Ca_cyt (Ca_nsr/Ca_cyt) was proposed as a novel threshold for Ca waves and Ca2+ alternans.
- This Ca_nsr/Ca_cyt ratio effectively explained the combined effects of Ca2+ release and uptake on alternans onset and correlated with SERCA function under different ischemic conditions.
Conclusions:
- The diastolic Ca_nsr/Ca_cyt ratio serves as a more comprehensive and accurate threshold for predicting Ca waves and Ca2+ alternans compared to individual Ca levels.
- This ratio can be utilized to differentiate calcium alternans arising from distinct ischemic conditions, reflecting SERCA pump function.
- The findings provide a new mechanistic insight into calcium alternans and offer a potential biomarker for assessing cardiac dysfunction during ischemia.
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