Calcium signaling in liver

In hepatocytes, hormones linked to the formation of the second messenger inositol 1,4,5-trisphosphate (InsP 3) evoke transient increases or spikes in cytosolic free calcium ([Ca 2+] i), that increase in frequency with the agonist concentration. These oscillatory Ca 2+ signals are thought to transmit the information encoded in the extracellular stimulus to down-stream Ca 2+-sensitive metabolic processes. We have utilized both confocal and wide field fluorescence microscopy techniques to study the InsP 3-dependent signaling pathway at the cellular and subcellular levels in the intact perfused liver. Typically InsP 3-dependent [Ca 2+] i spikes manifest as Ca 2+ waves that propagate throughout the entire cytoplasm and nucleus, and in the intact liver these [Ca 2+] i increases are conveyed through gap junctions to encompass entire lobular units. The translobular movement of Ca 2+ provides a means to coordinate the function of metabolic zones of the lobule and thus, liver function. In this article, we describe the characteristics of agonist-evoked [Ca 2+] i signals in the liver and discuss possible mechanisms to explain the propagation of intercellular Ca 2+ waves in the intact organ.