Ca²⁺ 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⁺.