A Study of Properties of the Ca2+ -Dependent Delayed Afterdepolarizations in a mathematical model for Human Ventricular Myocytes.

Navneet Roshan and Rahul Pandit
Indian Institute of Science


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 Na + - Ca 2+ exchanger and the SERCA pump uptake rate are the critical parameters for triggering DADs. We also show that the Na + -Ca 2+ 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.