Regulation of bile secretion by calcium signaling in health and disease

• Published in: Biochimica et biophysica acta. Molecular cell research 2018-11, Vol.1865 (11), p.1761-1770
• Main Authors: Trampert, David C., Nathanson, Michael H.
• Format: Article
• Language: English
• Subjects: Bile secretion; Calcium; Cholangiocyte; Cholestasis; Hepatocyte; Inositol 1,4,5-trisphosphate receptor
• ISSN: 0167-4889; 1879-2596
• DOI: 10.1016/j.bbamcr.2018.05.010

Calcium (Ca2+) signaling controls secretion in many types of cells and tissues. In the liver, Ca2+ regulates secretion in both hepatocytes, which are responsible for primary formation of bile, and cholangiocytes, which line the biliary tree and further condition the bile before it is secreted. Cholestatic liver diseases, which are characterized by impaired bile secretion, may result from impaired Ca2+ signaling mechanisms in either hepatocytes or cholangiocytes. This review will discuss the Ca2+ signaling machinery and mechanisms responsible for regulation of secretion in both hepatocytes and cholangiocytes, and the pathophysiological changes in Ca2+ signaling that can occur in each of these cell types to result in cholestasis. •Ca2+ signaling orchestrates secretion of bile from both hepatocytes and cholangiocytes.•In hepatocytes InsP3R-2 regulates the secretion of organic anions and bile acids via MRP2 and BSEP respectively.•In cholangiocytes InsP3R-3 contributes to the alkalinisation of bile via HCO3− secretion.•Gap junctions facilitate coordinated intercellular Ca2+ signaling across hepatocytes and cholangiocytes.•Impaired Ca2+ signaling is common in cholestasis and renders itself a useful target for therapeutics.