Bile canalicular secretion - tales from Vienna and Yale.

The isolated rat hepatocyte couplet was developed to facilitate studies of canalicular bile formation in a primary bile secretory unit in culture. This preparation enabled the first determination of electrical driving forces across the canalicular membrane in an intact hepatocyte. The basic electrical properties of the hepatocyte were able to be described using this model which also facilitated functional studies of canalicular bile formation using video and confocal imaging techniques. More recently isolated hepatocytes in collagen sandwich cultures have been adapted for the studies of bile formation in polarized hepatocytes requiring longer term experiments where proteins involved in the bile secretory process can be specifically knocked down using adenoviral siRNA techniques. This presentation reviews the historical development of the hepatocyte couplet preparations and the seminal contributions of Jürg Graf to this field.