Properties of intracellular Ca2+ waves generated by a model based on Ca(2+)-induced Ca2+ release.

摘要

Cytosolic Ca2+ waves occur in a number of cell types either spontaneously or after stimulation by hormones, neurotransmitters, or treatments promoting Ca2+ influx into the cells. These waves can be broadly classified into two types. Waves of type 1, observed in cardiac myocytes or Xenopus oocytes, correspond to the propagation of sharp bands of Ca2+ throughout the cell at a rate that is high enough to permit the simultaneous propagation of several fronts in a given cells. Waves of type 2, observed in hepatocytes, endothelial cells, or various kinds of eggs, correspond to the progressive elevation of cytosolic Ca2+ throughout the cell, followed by its quasi-homogeneous return down to basal levels. Here we analyze the propagation of these different types of intracellular Ca2+ waves in a model based on Ca(2+)-induced Ca2+ release (CICR). The model accounts for transient or sustained waves of type 1 or 2, depending on the size of the cell and on the values of the kinetic parameters that measure Ca2+ exchange between the cytosol, the extracellular medium, and intracellular stores. Two versions of the model based on CICR are considered. The first version involves two distinct Ca2+ pools sensitive to inositol 1,4,5-trisphosphate (IP3) and Ca2+, respectively, whereas the second version involves a single pool sensitive both to Ca2+ and IP3 behaving as co-agonists for Ca2+ release. Intracellular Ca2+ waves occur in the two versions of the model based on CICR, but fail to propagate in the one-pool model at subthreshold levels of IP3. For waves of type 1, we investigate the effect of the spatial distribution of Ca(2+)-sensitive Ca2+ stores within the cytosol, and show that the wave fails to propagate when the distance between the stores exceeds a critical value on the order of a few microns. We also determine how the period and velocity of the waves are affected by changes in parameters measuring stimulation, Ca2+ influx into the cell, or Ca2+ pumping into the stores. For waves of type 2, the numerical analysis indicates that the best qualitative agreement with experimental observations is obtained for phase waves. Finally, conditions are obtained for the occurrence of "echo" waves that are sometimes observed in the experiments.