Variation of calcium concentration in hepatocytes (liver cells) is known to modulate diverse cellular functions, including bile secretion, glucose and energy metabolism and vesicular trafficking. A major question in the study of calcium signalling in hepatocytes is how these distinct cellular processes are controlled and organised via coordinated spatial and temporal calcium signals.
Downstream cellular responses are controlled via intracellular calcium oscillations but the underlying mechanisms which shape these oscillations have yet to be elucidated. We are interested in determining the effects of various types of calcium feedback mechanisms such as calcium feedback on Phospholipase C (PLC) and the calcium-mediated protein kinase C (PKC) feedback on the hormone receptor have on the whole-cell calcium signals. Recent experimental data suggests that hormone-induced calcium oscillations require positive calcium feedback on PLC to generate inositol trisphosphate oscillations, yielding cross-coupling between calcium and inositol trisphosphate. Furthermore, it appears that there is also a negative feedback pathway, cross-coupling PLC activation to PKC, which serves to terminate calcium spikes.
This talk will discuss recent progress in construction and analysis of a model of calcium oscillations that incorporates the new experimental results about likely feedback mechanisms in hepatocytes.