1. Spatiotemporal features of Ca2+ buffering and diffusion in atrial cardiac myocytes with inhibited sarcoplasmic reticulum.
- Author
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Michailova A, DelPrincipe F, Egger M, and Niggli E
- Subjects
- Adenosine Triphosphate metabolism, Animals, Buffers, Calcium Signaling drug effects, Cells, Cultured, Computer Simulation, Diffusion, Guinea Pigs, Heart Atria drug effects, Heart Atria metabolism, Membrane Potentials drug effects, Membrane Potentials physiology, Microscopy, Confocal methods, Microscopy, Fluorescence methods, Models, Chemical, Muscle Cells cytology, Muscle Cells drug effects, Myocardium metabolism, Patch-Clamp Techniques, Ryanodine pharmacology, Sarcoplasmic Reticulum drug effects, Thapsigargin pharmacology, Calcium metabolism, Calcium Signaling physiology, Models, Cardiovascular, Muscle Cells physiology, Sarcoplasmic Reticulum metabolism
- Abstract
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+).
- Published
- 2002
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