David Conesa: Analysis of homeostatic regulation in cardiac cells

Calcium ions play a leading role in heart contraction. Heart beats at a pace given by the sinoatrial node where an action potential is generated, then propagated to the rest of cardiac cells. Contractile force depends on calcium transient in the cytosol of cardiomyocytes during a process called Excitation-Contraction Coupling, which starts with this action potential. This transient, in turn, depends on the total pre-systolic level of Ca2+ in the cytosol (free and buered) and in the SR when the homeostatic regime is reached. Since large calcium loads lead to large contractions and vice versa cell functionality is thus directly related with the homeostatic balance. Calcium homeostasis is reached when Ca2+ concentrations return along consecutive beats to the same values on average.

In this work we have analyzed the main calcium currents involved in calcium handling in cardiomyocytes during a standardized beat in order to better understand how homeostasis is reached and how changes in properties of some proteins make the system to reach dierent homeostatic states, aecting the general heart function. Indeed, for the first time, we will show that is possible to predict heart tissue function from channel measurements. This is the first time ever that a theory has been produced, and tested numerically, which might be able to breach the gap between the relatively easy to do experiments in isolated cardiomyocytes and the function of the whole heart.