Lack of correlation between CFTR expression, CFTR Cl- currents, amiloride-sensitive Na+ conductance, and cystic fibrosis phenotype

Cystic fibrosis (CF) is characterized by defective Cl- and enhanced Na+ con ductance, both due to malfunction of the cystic fibrosis transmembrane cond uctance regulator (CFTR) protein in airway epithelial cells. In the present study we examined whether expression of CFTR mRNA (CFTR messenger ribonucl eic acid) is different in airway epithelia derived from either CF patients or healthy volunteers. Moreover, we tried to correlate differences in epith elial Cl- and Na+ conductance with the level of CFTR mRNA expression and st udied whether these properties correlate to the clinical phenotype of CF pa tients. To that end, CFTR mRNA was determined by means of quantitative reve rse transcriptase polymerase chain reaction (RT-PCR) and cyclic adenosine m onophosphate (cAMP)-activated Cl- and epithelial Na+ conductances were exam ined in airway epithelial cells using microelectrode techniques. Complement ary in vitro data were obtained from cultured CF and non-CF airway epitheli al cell lines. Genotype and Shwachman score were assessed for each patient. We found variable levels of CFTR mRNA expression in airway cells of both CF patients and healthy volunteers. As expected, epithelial Na+ conductance w as enhanced and CFTR Cl- conductance was absent in airway cells from CF pat ients. However, CFTR mRNA expression did not correlate with either electrop hysiological properties or Shwachman scores obtained from CF patients. In a ddition, CFTR mRNA expression did not correlate to Cl- conductance in cultu red CF and non-CF airway epithelial cells. These results indicate a lack of correlation between levels of CFTR mRNA and CFTR function, and that only s mall amounts of CFTR are required for expression of the CFTR Cl- conductanc e. (C) 1999 Wiley-Liss.