Key result
In a mathematical model of human ventricular myocytes, the Na+-Ca2+ exchanger conductance increased DAD amplitude, while the SERCA pump uptake rate increased DAD frequency.
Why the study?
Delayed afterdepolarizations can be arrhythmogenic and may arise from diseased conditions or mutations affecting ion channels, exchangers, or pumps, but reproducing these complex changes experimentally is difficult.
Computational modeling of human ventricular myocytes demonstrates that the Na+-Ca2+ exchanger and SERCA pump are critical parameters for triggering and modulating delayed afterdepolarizations.
Answers are grounded in this paper and cite their sources.
Model findings highlight Na-Ca exchanger and SERCA as DAD modulators; hypothesis-generating, leaves clinical translation open.
Delayed afterdepolarizations (DADs), observed in cardiac myocytes can be arrhythmogenic. These DADs may arise in diseased conditions or mutations that induce numerous changes in the expression levels of exchangers, ion channels, or ionic pumps. It is difficult to reproduce these changes in experiments; therefore, we carry out a detailed in silico study of these modifications in the human ventricular myocyte model due to ten Tusscher and Panfilov (TP06). We find three types of DADs. Furthermore, by using parameter-sensitivity analysis, we show that the <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">Na^ + - Ca2 +</tex> exchanger and the SERCA pump uptake rate are the critical parameters for triggering DADs. We also show that the <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">Na^ + - Ca2 +</tex> conductance increases the DAD amplitude, whereas the SERCA uptake rate increases the frequency of the DADs. We obtain a phase diagram for the TP06 model and present regions of parameter space which show various types of DADs.
No takes yet. Share an insight, caveat, or question.
Roshan et al. (2021) studied Arrhythmogenic delayed afterdepolarizations. Parameter modifications (Na+-Ca2+ exchanger and SERCA pump uptake rate) vs. Baseline model parameters was evaluated on Occurrence, amplitude, and frequency of delayed afterdepolarizations (DADs). In a mathematical model of human ventricular myocytes, the Na+-Ca2+ exchanger conductance increased DAD amplitude, while the SERCA pump uptake rate increased DAD frequency.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: