A MODIFIED MATHEMATICAL MODEL OF HUMAN VENTRICULAR CARDIOMYOCYTE INCORPORATING SEPARATE T-TUBULAR AND SURFACE DYADS AND SUBMEMBRANE SPACES

Intracellular Ca2+ load and Ca2+ transient are considerably dependent on distribution of sarcolemmal Ca2+ pump and Na+-Ca2+ exchanger between the t-tubular and surface membranes in the presence of separate dyadic and subsarcolemmal spaces in rat ventricular cell model. To explore analogical phenomenon in human, we modified our previously published model of human ventricular myocyte. When the t-tubular fractions of Na+-Ca2+ exchanger and of sarcolemmal Ca2+ pump were increased to the newly proposed value of 0.95 in the modified model, the following changes were observed at 1 Hz steady-state stimulation: a shortening of the action potential duration at 90% repolarisation by 6% and an increase of the cytosolic Ca2+ transient by 22%. Further analysis revealed a critical role of Ca2+ concentration changes in the subsarcolemmal spaces and consequent change in cellular Ca2+ cycling in this effect