Phenotypic control of gap junctional communication by cultured alveolar epithelial cells

We examined phenotype-specific changes in gap junction protein [connexin (C x)] expression and function by cultured rat alveolar type II cells. Type II cells cultured on extracellular matrix in medium containing keratinocyte g rowth factor (KGF) and 2% fetal bovine serum (FBS; KGF/2) retained expressi on of surfactant protein C and the 180-kDa lamellar body membrane protein ( lbm180). These markers were lost when cells were cultured in medium contain ing 10% FBS (MEM/10). With RT-PCR, cells cultured in MEM/10 showed transien t increases in Cx43 and Cx46 mRNA expression, whereas Cx32 and Cx26 decreas ed and Cx30.3 and Cx37 were unchanged. Transient changes in Cx32, Cx43, and Cx46 protein expression were confirmed by immunoblot. In contrast, cells c ultured in KGF/2 retained expression of Cx32 and showed increased expressio n of Cx30.3 and Cx46 mRNAs, compared with that in day 0 cells. With immunof luorescence microscopy, Cx32 and Cx43 were at the plasma membrane of cells grown in KGF/2, whereas Cx46 was exclusively intracellular. Type II cells c ultured in MEM/10 showed similar to 3- to 4-fold more intercellular transfe r of microinjected lucifer yellow through gap junctions than cells grown in 2% FBS. Thus type II cells dynamically alter gap junctional communication, and distinct alveolar epithelial cell phenotypes express different connexi ns.