The location of hepatocytes in the rat liver acinus determines their sensitivity to calcium-mobilizing hormones

Abstract

Background and Aims: In multicellular systems of rat hepatocytes and in the intact liver, inositol 1,4,5-trisphosphate (IP3)-dependent agonists induce sequentially ordered calcium ion signals. The mechanisms by which sequential waves are oriented from one hepatocyte to another are unknown. The aim of this study was to investigate the relationship between hepatocyte location in the acinus and cellular sensitivity to noradrenaline, vasopressin, adenosine triphosphate, and angiotensin II. Methods: Periportal (PP) and pericentral (PC) rat hepatocyte suspensions, isolated by the digitonin collagenase technique, were loaded with quin2-acetoxymethyl ester, and hormonal responses were studied in a spectrofluorimeter. The function of the IP3 receptor was studied by measuring the IP3-mediated 45Ca2+ release from permeabilized PP and PC hepatocytes. Results: Increases in noradrenaline and vasopressin-induced intracellular Ca2+ concentration were greater in PC than in PP hepatocytes. In contrast, PP cells were more responsive than PC cells to adenosine triphosphate, and angiotensin II induced similar intracellular Ca2+ concentration increases in both hepatocyte populations. In permeabilized PP and PC hepatocytes, internal Ca2+ stores showed the same loading kinetics, the responses to IP3 were similar, and the sizes of the IP3-sensitive compartment were not different. Conclusions: Hepatocyte location in the acinus determines cellular sensitivity to Ca2+-mobilizing agonists. Intercellular Ca2+ waves in the liver could be driven by sensitivity gradients along the hepatocyte plate.