Spatio-temporal modelling explains the effect of reduced plasma membrane Ca2+ efflux on intracellular Ca2+...

In many non-excitable eukaryotic cells, including hepatocytes, Ca(2+) oscillations play a key role in intra- and intercellular signalling, thus regulating many cellular processes from fertilisation to death. Therefore, understanding the mechanisms underlying these oscillations, and consequently understanding how they may be regulated, is of great interest. In this paper, we study the influence of reduced Ca(2+) plasma membrane efflux on Ca(2+) oscillations in hepatocytes. Our previous experiments with carboxyeosin show that a reduced plasma membrane Ca(2+) efflux increases the frequency of Ca(2+) oscillations, but does not affect the duration of individual transients. This phenomenon can be best explained by taking into account not only the temporal, but also the spatial dynamics underlying the generation of Ca(2+) oscillations in the cell. Here we divide the cell into a grid of elements and treat the Ca(2+) dynamics as a spatio-temporal phenomenon. By converting an existing temporal model into a spatio-temporal one, we obtain theoretical predictions that are in much better agreement with the experimental observations.