It therefore suggests the regulatory interaction between the two channels is far more complicated than originally thought, which may possibly explain why ENaC inhibitors failed to rescue CF airway (Graham et al., 1993; Pons et al., 2000; Hirsh et al., 2004), since a high degree of ENaC inhibition would not enhance CFTR but result in further CFTR deficiency. The gene discussed is CFTR; the disease is cystic fibrosis.