Cystic fibrosis transmembrane conductance regulator and Na⁺ channel subunits mRNA transcripts, and Cl^- efflux, show a different distribution in rat duodenum and colon

Aim: We compared the distribution and putative association of Cl^- channel transport, CFTR mRNA transcripts, and Na⁺ channel (ENaC) α- and β-subunit mRNA transcripts in villus and crypt epithelial cells of duodenum, with corresponding surface and crypt cells of colon from sodium-depleted rats. Methods: Cells were loaded with ³⁶Cl^- and forskolin-stimulated efflux was determined. RT-PCR was performed for CFTR mRNA transcripts and ENaC α- and β-subunit mRNA. Duodenal epithelial cell response to VIP was assessed by measuring intracellular cAMP. Results: Forskolin-stimulated Cl^- efflux occurred with decreasing magnitude in duodenal crypt, duodenal villus, colonic crypt and colonic surface cells in Na⁺-depleted animals. CFTR expression was correlated directly with Cl^- efflux (r = 0.91, P < 0.01). Na⁺ channel α-subunit was expressed in colon and duodenum in animals fed diets with a high or low sodium content. While the β-subunit mRNA was detected in the colon of sodium-restricted rats, it was absent in the duodenum under control conditions and after Na⁺ restriction. There was an inverse correlation between mRNA transcripts for CFTR and the ENaC α-subunit (r = -0.93, P < 0.003) and β-subunit (r = -0.91, P < 0.004) in colon. VIP-stimulated cAMP in duodenal epithelial cells was greater in crypt than villus (P < 0.05). Conclusion: Cl^- efflux, CFTR transcription and forskolin-stimulated cAMP activity occur in both crypt and villus epithelial cells in duodenum. Possible interaction between CFTR and Na⁺ channels is apparently limited to parts of the colonic crypt. Lack of duodenal β-subunit expression makes ENaC activity unlikely.