Alterations of tight and gap junctions in mouse hepatocytes following administration of colchicine.

Abstract

Following the administration of colchicine at a dosage (1 mg/mouse) known to cause an antimicrotubular effect, membranes as well as tight and gap junctions of hepatocytes were studied using the thin-sectioning and freeze-fracturing technique. As early as 1 h after administration of colchicine the intercellular spaces were dilated and vacuoles were visible within the cytoplasm. The bile canaliculi became enlarged, and after lanthanum perfusion the tracer was found in the canalicular lumen, i.e., the tight junctions became permeable to the tracer. These findings correlated with a disorganized arrangement of the tight junctional strands of the zonula occludens. In some regions the strands showed interruptions and frequently ended freely in a diffuse pattern on the plasma membrane. Proliferation of tight junctions could be observed at various locations on the plasma membrane. The gap junctions also exhibited alterations. They showed an irregular outline with outpouchings, in addition to an enlargement in their total area from approximately 0.5 microns 2 in controls up to approximately 2 microns 2 in treated mice. The surface area occupied by these junctions increased from 4% (controls) to 20% (treated) of the hepatic plasma membrane. In the cytoplasm of hepatocytes from colchicine-treated mice gap-junctional vesicles were frequently observed. In view of the antimicrotubular effect of colchicine it is tentatively suggested that the intact microtubular system of the cell may play a decisive role in the regular formation of gap and tight junctions, either directly or indirectly via microfilaments.