Earlier simulation studies have modelled the nucleus as a region lacking a releasable calcium pool with lower diffusion coefficient (about 50 μm2/s) compared with cytoplasm (about 300 μm2/s), where nuclear calcium rises only because of passive diffusion [1]. However, the magnitude and duration of nuclear calcium transient can be both significantly greater than that of cytosolic calcium transient, which indicates other potential nuclear calcium release sources [2]. Given the importance of nuclear calcium in the regulation gene transcription and expression, we introduce a nulcear envelope into the 3Dv E-Cell, which has been used to model stochastic intracellular calcium wave phenomena of an isolated ventricular cell [3], as a barrier with low diffusion coefficient DNE < 5 μm2/s to maintain spatial heterogeneity, and nuclear calcium handling as a CICR type process with longer Ca2+ release duration (about 200 ms) and relative high diffusion coefficient (about 200 μm2/s). A nuclear envelope with a very low diffusion coefficient (DNE = 0.1 μm2/s), isolates the nucleus from the cytosol, and cytosolic calcium waves neither enter the nucleus nor initiate nuclear calcium transients. The nucleus acts simply as an obstacle that splits the calcium wave front into two fronts that travel around the nucleus. For intermediate values (DNE = 1.0 μm2/s) a Ca2+ wave can trigger a confined nuclear Ca2+ transient, and lead to a nuclear Ca2+ excitation. Since the nucleus has a much longer Ca2+ release duration, nuclear Ca2+ concentration remains at a high level for a relatively long period after the cytosolic Ca2+ wave passed. At higher values (DNE = 5.0 μm2/s) a nuclear calcium transient can be activated when cytosolic calcium wave reached an end of the elongated nucleus. The nuclear Ca2+ transient can re-invade neighbouring cytosol and trigger a Ca2+ wave. This can allow a Ca2+ spark located near the nucleus to be amplified by the nuclear transient and nuclear envelope, and initiate a spontaneous cytosolic Ca2+ wave due to a high DNE. Examples of these phenomena are illustrated in Fig. 1.
University of Manchester (2007) Proc Physiol Soc 8, PC1
Poster Communications: Cytosolic and nuclear calcium dynamics interaction in a three-dimensional ventricular E-Cell (3Dv E-Cell)
P. Li1, A. V. Holden1
1. Institute of Membrane and Systems Biology, University of Leeds, Leeds, United Kingdom.
View other abstracts by:
Fig. 1 Effects of the nuclear envelope diffusion coefficient on nuclear-cytosolic calcium transient coupling on intracellular calcium wave patterns. Isochrones of 20μM [Ca2+] are shown with time steps of 50ms. At t = 0ms, a stimulus is applied at the bottom end of the cell by increasing calcium concentration to 50 μM, with (a) DNE = 0.1 μm2/s, (b) DNE = 1.0 μm2/s, (c) DNE = 5.0 μm2/s.
Where applicable, experiments conform with Society ethical requirements.