Compensatory and decompensatory alterations in cardiomyocyte Ca2+ dynamics in hearts with diastolic dysfunction following aortic banding

摘要

Key points class="unordered" style="list-style-type:disc" id="tjp12242-list-0001">At the cellular level cardiac hypertrophy causes remodelling, leading to changes in ionic channel, pump and exchanger densities and kinetics.Previous studies have focused on quantifying changes in channels, pumps and exchangers without quantitatively linking these changes with emergent cellular scale functionality.Two biophysical cardiac cell models were created, parameterized and validated and are able to simulate electrophysiology and calcium dynamics in myocytes from control sham operated rats and aortic‐banded rats exhibiting diastolic dysfunction.The contribution of each ionic pathway to the calcium kinetics was calculated, identifying the L‐type Ca²⁺ channel and sarco/endoplasmic reticulum Ca²⁺ATPase as the principal regulators of systolic and diastolic Ca²⁺, respectively.Results show that the ability to dynamically change systolic Ca²⁺, through changes in expression of key Ca²⁺ modelling protein densities, is drastically reduced following the aortic banding procedure; however the cells are able to compensate Ca²⁺ homeostasis in an efficient way to minimize systolic dysfunction.