Ca(2+) signaling in cells is largely governed by Ca(2+) diffusion
and Ca(2+) binding to mobile and stationary Ca(2+) buffers, including
organelles. To examine Ca(2+) signaling in cardiac atrial myocytes,
a mathematical model of Ca(2+) 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 Ca(2+)
signals in terms of amplitude, time course, and spatial features.
For experimental reference data, L-type Ca(2+) currents were recorded
from atrial cells with the whole-cell voltage-clamp technique. Ca(2+)
signals were simultaneously imaged with the fluorescent Ca(2+) indicator
Fluo-3 and a laser-scanning confocal microscope. The simulations
indicate that in atrial myocytes lacking T-tubules, Ca(2+) movement
from the cell membrane to the center of the cells relies strongly
on the presence of mobile Ca(2+) buffers, particularly when the sarcoplasmic
reticulum is inhibited pharmacologically. Furthermore, during the
influx of Ca(2+) 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(2+) affinity, ATP acts as a significant buffer and carrier for
Ca(2+), even at the modest elevations of Ca(2+)(i) reached during
influx of Ca(2+).