Altered expression and function of hepatocyte gap junctions following common bile duct ligation in the rat. Fallon, Michael B., Michael H. Nathanson, Albert Mennone, Juan C. Saez, Angela D. Burgstahler, and James M. Anderson. Department of Internal Medicine and The Liver Center, Yale University School of Medicine, New Haven, CT 06510, and Departamento de Ciencias, Fisioloqicas, Facultad de Ciencias Biol[acute]ogicas, Pontificia, Universiadad, Catolica de Chile, Santiago, Chile.
APStracts 2:0063C, 1995.
Gap junction channels allow intercellular exchange of ions and small molecules between adjacent cells. Such communication coordinates cellular and organ function in tissues, although it is unclear if altered gap junction expression and communication contribute to organ dysfunction in pathologic states. We examined the immunofluorescent (IF) localization and mRNA and protein levels of the two hepatocyte gap junction proteins connexin32 and 26, after hepatic injury induced by common bile duct ligation (CBDL) in the rat. Intercellular communication was measured by comparing gap junction-mediated coordination of hormone-induced Ca++ signals in isolated rat hepatocyte couplets (IRHC) from control and CBDL animals. Connexin32 plasma membrane IF, protein and mRNA levels decreased markedly early after CBDL and remained low at 14 days. Connexin26 plasma membrane IF and protein levels also decreased markedly after CBDL, but mRNA levels rose, and a partial return in membrane IF and protein levels were noted at 9 and 14 days. Coordination of vasopressin-induced Ca++ signals between cells in IRHCs 1 day after CBDL was significantly impaired compared to controls. These results demonstrate that hepatocyte gap junction communication is impaired early after CBDL, due to decreased connexin protein levels. Disruption of gap junctions after CBDL may contribute to loss of hepatic functions which depend on gap junction communication. 

Received 6 July 1994; accepted in final form 28 November 1994.
APS Manuscript Number C0388-4.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 27 February 1995.