What can we learn from the irregularity of Ca2+ oscillations?

Abstract

In most cells, Ca(2+) increases in response to external stimulation are organized in the form of oscillations and waves that sometimes propagate from one cell to another. Numerous experimental and theoretical studies reveal that this spatiotemporal organization contains a non-negligible level of stochasticity. In this study, we extend the previous work based on a statistical analysis of experimental Ca(2+) traces in isolated, hormone-stimulated hepatocytes and on stochastic simulations of Ca(2+) oscillations based on the Gillespie's algorithm. Comparison of the coefficients of variation in the periods of experimental and simulated Ca(2+) spikes provides information about the clustering and the specific subtypes of the Ca(2+) channels. In hepatocytes coupled by gap junctions, the global perfusion with a hormone leads to successive Ca(2+) responses, giving the appearance of an intercellular wave. Statistical analysis of experimental Ca(2+) oscillations in coupled hepatocytes confirms that this coordinated Ca(2+) spiking corresponds to a phase wave but suggests the existence of an additional coupling mechanism.