Morphogenesis of the epithelial cell transporting phenotype: synthesis and distribution of ion channels

The exchange of substances between higher organisms and the environment takes place across epithelia consisting of one or more cell layers. To perform this function, epithelial cells have two basic differentiated properties: 1) they form tight junctions (TJs) that seal the extracellular space, and 2) they are polarized into an apical and a basolateral domain, with entirely different structural, biochemical and physiological properties. Our understanding of the mechanisms involved in the expression of these properties has been greatly enhanced by the availability of epithelial cell lines that form TJs and polarize in vitro under conditions suitable for experimental control. In this article we summarize our studies on the synthesis and polarized expression of ion channels in epithelial cells. MDCK cells have four types of K+ channels in the apical domain, and a fifth one in the basolateral domain. The basolateral side also has a population of CI- channels. Each type of channel is absolutely polarized. Harvesting with trypsin-EDTA reduces the area of the plasma membrane by 50% and the channel population by 90%. Upon plating, these channels are recovered within a few hours. We describe here the main extracellular and intracellular mechanisms involved in these phenomena.