However, the basis of the low volume hypothesis, including ENaC hyperactivity by loss of CFTR function and Na+ hyperabsorption in CF epithelia is not supported by several experimental approaches, such as patch-clamp studies of ENaC channel activity (Nagel et al., 2005), the measurement of transepithelial Na+ absorption (Chen et al., 2010; Itani et al., 2011; Willumsen and Boucher, 1991a, b) and amiloride-sensitive changes in short-circuit currents of cultured pig airway epithelia (Chen et al., 2010). This evidence concerns the gene CFTR and cystic fibrosis.