Cellular Physiology

        In hepatocytes, Ca2+ regulates glucose homeostasis, bile synthesis and secretion, protein synthesis, lipid metabolism, and the transport of xenobiotic compounds. Ca2+ also acts as regulator of proliferation, growth, and apoptosis. A complex system of Ca2+ channels, primary and secondary active transporters, and Ca2+ binding proteins are essential for cellular Ca2+ homeostasis and, in particular, in achieving precise concentrations of Ca2+ at specific locations within the cell at particular points in time. While many of these processes are common in most cell types, there are two major systems involved in Ca2+ entry from the extracellular fluid. In non-excitable cells, store-operated Ca2+ channels (SOCs) and receptor-activated Ca2+ channels provide major pathways for Ca2+ entry. Physiologically, the activity of both SOCs and receptor activated Ca2+ channels is controlled by hormone binding to G-protein- or tyrosine kinase-coupled receptors on the plasma membrane. 
        In our research into the role of Ca2+ channels in liver function and disease we use a range of techniques of electrophysiology, molecular biology, microscopy, and protein chemistry. Among those are: measurement of membrane currents by patch clamping, quantitative RT-PCR, immunofluorescence and western blotting, site-directed mutagenesis, RNA interference, measurement of cytoplasmic Ca2+ using fluorescent reporters, live cell imaging, and confocal microscopy.

Some Key Publications

1. Aromataris, E. C., M.L. Roberts, G.J. Barritt, and G.Y. Rychkov. 2006. Glucagon activates Ca2+ and Cl- channels in rat hepatocytes. Journal of Physiology 573:611-625
2. Rychkov, G.Y., T. Litjens, M.L. Roberts, and G.J. Barritt. 2005. ATP and vasopressin activate a single type of store-operated Ca2+ channel, identified by patch-clamp recording, in rat hepatocytes. Cell Calcium. 37:183-91.
3. Litjens T., T. Nguyen, J. Castro, E. C. Aromataris, L. Jones, G.J. Barritt and G.Y. Rychkov. 2007. Phospholipase C-γ 1 is required for the activation of store-operated Ca2+ channels in liver cells. Biochemical Journal. doi:10.1042/BJ20061762
4. Litjens, T., M.L. Harland, M.L. Roberts, G.J. Barritt, and G.Y. Rychkov. 2004. Fast Ca2+-dependent inactivation of the store-operated Ca2+ current (ISOC) in liver cells: a role for calmodulin. Journal of Physiology. 558:85-97.