Intrahepatic cholestasis as a canalicular motility disorder. Evidence using cytochalasin.

A rich network of actin-containing microfilaments are associated with the plasma membrane of the liver cells. These filaments are especially numerous in the pericanalicular region. Recently, active contractions of bile canaliculi have been observed in normal coupled isolated hepatocytes. In this report, we document that this motility behavior is abolished by cytochalasins B and D. Other cytoplasmic contractile movements are also reduced or lost after a brief initial period of enhanced surface activity with the formation of zeiotic blebs. The lack of contractile activity of bile canaliculi is accompanied by the gradual dilation of canalicular lumina. Since there is overwhelming evidence that the functional effects of the cytochalasins on cell motility are due to their effects on actin filaments, we propose that the altered canalicular contractility observed is due to the effects of cytochalasin on pericanalicular actin filaments. If bile canalicular contractility is a requirement for normal bile flow, then interference with this mechanism may be a factor in the pathogenesis of some types of intrahepatic cholestasis.