Spatiotemporal Features of Ca2+ Buffering and Diffusion in Atrial Cardiac Myocytes with Inhibited Sarcoplasmic Reticulum

Ca signaling in cells is largely governed by Ca diffusion and Ca binding to mobile and stationary Ca buffers, including organelles. To examine Ca signaling in cardiac atrial myocytes, a mathematical model of Ca was developed which represents several subcellular compartments, including a subsarcolemmal space with restricted diffusion, a myofilament space, and the cytosol. The model was used to quantitatively simulate experimental Ca terms of amplitude, time course, and spatial features. For experimental reference data, L-type Ca currents were recorded from atrial cells with the whole-cell voltage-clamp technique. Ca signals were simultaneously imaged with the fluorescent indicator Fluo-3 and a laser-scanning confocal microscope. The simulations indicate that in atrial myocytes lacking T-tubules, Ca movement from the cell membrane to the center of the cells relies strongly on the presence of mobile Ca buffers, particularly when the sarcoplasmic reticulum is inhibited pharmacologically. Furthermore, during the influx of Ca large and steep concentration gradients are predicted between the cytosol and the submicroscopically narrow subsarcolemmal space. In addition, the computations revealed that, despite its low Ca affinity, ATP acts as a significant buffer and , even at the modest elevations of [Ca ] i reached during influx of Ca