Hormones increase mRNA of cyclic-nucleotide-gated cation channels in airway epithelia

Previous studies have shown that the mRNA of cyclic-nucleotide-gated nonsel ective cation (CNG) channels is expressed in rat airway epithelia and that these channels contribute to sodium-mediated short-circuit currents in cult ured rat tracheal epithelia. Patch-clamp studies from human A549 cells indi cate that these channels contribute to cGMP-stimulated L-cis-diltiazemand d ichlorobenzamil-inhibited whole-cell sodium currents. This study demonstrat es that mRNA for primary and secondary subunits of CNG channels, h alpha CN G1 and h beta CNG1 respectively, are expressed in several human airway cell lines, including normal and cystic fibrosis bronchial airway cells, in nor mal and cystic fibrosis tracheal airway cell lines and nasal polyp tissue f rom a cystic fibrosis patient. The mRNA of r alpha CNG1 in rat lung increas ed in response to increased circulating glucocorticoids and decreased in an imals with lowered circulating glucocorticoids after aminoglutethimide trea tment. Likewise the mRNA of h alpha CNG1 increased in the presence of gluco corticoids in cultured alveolar airway cells. The mRNA of alpha CNG1 in rat lung was also increased in response to a low-salt diet and lowered in anim als fed a high-salt diet. Likewise the mRNA of alpha CNG1 was increased in response to increased aldosterone and decreased in animals given spironolac tone. These results suggest that mRNA for alpha CNG1 increases in response to elevated glucocorticoids or mineralocorticoids. Because alpha CNG1 is a functional sodium entry channel in both rat and human airway epithelial cel ls, if channel protein is also elevated this channel could mediate an incre ase in sodium absorption across lung epithelia in response to circulating h ormones.