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

AbstractCa2+ signaling in cells is largely governed by Ca2+ diffusion and Ca2+ binding to mobile and stationary Ca2+ buffers, including organelles. To examine Ca2+ signaling in cardiac atrial myocytes, a mathematical model of Ca2+ diffusion 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 Ca2+ signals in terms of amplitude, time course, and spatial features. For experimental reference data, L-type Ca2+ currents were recorded from atrial cells with the whole-cell voltage-clamp technique. Ca2+ signals were simultaneously imaged with the fluorescent Ca2+ indicator Fluo-3 and a laser-scanning confocal microscope. The simulations indicate that in atrial myocytes lacking T-tubules, Ca2+ movement from the cell membrane to the center of the cells relies strongly on the presence of mobile Ca2+ buffers, particularly when the sarcoplasmic reticulum is inhibited pharmacologically. Furthermore, during the influx of Ca2+ 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 Ca2+ affinity, ATP acts as a significant buffer and carrier for Ca2+, even at the modest elevations of [Ca2+]i reached during influx of Ca2+