Calcium in hepatocytes modulates diverse 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. In particular, we are interested in the effect of protein kinase C (PKC) on the purinergic family of receptors. Recent data has shown that the activation of different receptors within the family of purinergic receptors generate qualitatively different calcium responses. It is believed that PKC differentially regulates each receptor resulting in distinct calcium response patterns. Furthermore, multiple pools of PKC, with unique activation pathways, are understood to exist in the cell with discrete downstream targets.
We 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. Our model suggests that multiple, uniquely activated, PKC feedback loops acting on unique cellular substrates, present in the cell coordinate to determine the qualitative behaviour of calcium oscillations in hepatocytes.
