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Journal of Histochemistry and Cytochemistry, Vol. 46, 405-410, Copyright © 1998, The Histochemical Society, Inc.

ARTICLE

Expression, Distribution, and Activity of Na+,K+-ATPase in Normal and Cholestatic Rat Liver

Lukas Landmanna, Sabine Angermüllerb, Christoph Rahnera, and Bruno Stiegerc
a Department of Anatomy, University of Basel, Switzerland
b Department of Anatomy and Cell Biology II, University of Heidelberg, Germany
c Division of Clinical Pharmacology, Department of Medicine, University Hospital, Zürich, Switzerland

Correspondence to: Lukas Landmann, Dept. of Anatomy, Pestalozzistr. 20, CH-4056 Basel, Switzerland.

Hepatocellular Na+,K+-ATPase is an important driving force for bile secretion and has been localized to the basolateral plasma membrane domain. Cholestasis or impaired bile flow is known to modulate the expression, domain specificity, and activity of various transport systems involved in bile secretion. This study examined Na+,K+-ATPase after ethinylestradiol (EE) treatment and after bile duct ligation (BDL), two rat models of cholestasis. It applied quantitative immunoblotting, biochemical and cytochemical determination of enzyme activity, and immunocytochemistry to the same livers. The data showed a good correlation among the results of the different methods. Neither EE nor BDL induced alterations in the subcellular distribution of Na+,K+-ATPase, which was found in the basolateral but not in the canalicular (apical) plasma membrane domain. Protein expression and enzyme activity showed a small (~10%) decrease after EE treatment and a similar increase after BDL. These modest changes could not be detected by immunofluorescence, immuno EM, or cytochemistry. The data, therefore, demonstrate that Na+,K+-ATPase is only slightly affected by EE and BDL. They suggest that other components of the bile secretory apparatus that take effect downstream of the primary basolateral driving force may play a more prominent role in the pathogenesis of cholestasis. (J Histochem Cytochem 46:405–410, 1998)

Key Words: Na+,K+-ATPase, rat liver, cholestasis, ethinylestradiol, bile duct ligation, Western blotting, enzyme activity, cytochemistry, immunocytochemistry, immuno EM


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