Different densities of Na-Ca exchange current in T-tubular and surface membranes and their impact on cellular activity in a model of rat ventricular cardiomyocyte

Abstract

The ratio of densities of Na-Ca exchanger current (INaCa) in the t-tubular and surface membranes (INaCa-ratio) computed from the values of INaCa and membrane capacitances (Cm) measured in adult rat ventricular cardiomyocytes before and after detubulation ranges between 1.7 and 25 (potentially even 40). Variations of action potential waveform and of calcium turnover within this span of the INaCa-ratio were simulated employing previously developed model of rat ventricular cell incorporating separate description of ion transport systems in the t-tubular and surface membranes. The increase of INaCa-ratio from 1.7 to 25 caused a prolongation of APD (duration of action potential at 90% repolarisation) by 12, 9, and 6% and an increase of peak intracellular Ca2+ transient by 45, 19, and 6% at 0.1, 1, and 5Hz, respectively. The prolonged APD resulted from the increase of INaCa due to the exposure of a larger fraction of Na-Ca exchangers to higher Ca2+ transients under the t-tubular membrane. The accompanying rise of Ca2+ transient was a consequence of a higher Ca2+ load in sarcoplasmic reticulum induced by the increased Ca2+ cycling between the surface and t-tubular membranes. However, the reason for large differences in the INaCa-ratio assessed frommeasurements in adult rat cardiomyocytes remains to be explained.