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 ([Ca2+](i)), that increase in frequency with the agonist concentration. These oscillatory Ca2+ signals are thought to transmit the information encoded in the extracellular stimulus to down-stream Ca2+-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 [Ca2+](i) spikes manifest as Ca2+ waves that propagate throughout the entire cytoplasm and nucleus, and in the intact liver these [Ca2+](i) increases are conveyed through gap junctions to encompass entire lobular units. The translobular movement of Ca2+ 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 [Ca2+](i) signals in the liver and discuss possible mechanisms to explain the propagation of intercellular Ca2+ waves in the intact organ. (C) 2005 Elsevier Ltd. All rights reserved.