Examining basal chloride transport using the nasal potential difference response in a murine model

Epithelia of humans and mice with cystic fibrosis are unable to secrete chl oride in response to a chloride gradient or to cAMP-elevating agents. Bioel ectrical properties measured using the nasal transepithelial potential diff erence (TEPD) assay are believed to reflect these cystic fibrosis transmemb rane conductance regulator (CFTR)-dependent chloride transport defects. Alt hough the response to forskolin is CFTR mediated, the mechanisms responsibl e for the response to a chloride gradient are unknown. TEPD measurements pe rformed on inbred mice were used to compare the responses to low chloride a nd forskolin in vivo. Both responses show little correlation between or wit hin inbred strains of mice, suggesting they are mediated through partially distinct mechanisms. In addition, these responses were assayed in the prese nce of several chloride channel inhibitors, including DIDS, diphenylamine-2 -carboxylate, glibenclamide, and 5-nitro-2-(3-phenylpropylamino)-benzoic ac id, and a protein kinase A inhibitor, the Rp diastereomer of adenosine 3', 5'-cyclic monophosphothioate (Rp-cAMPS). The responses to low chloride and forskolin demonstrate significantly different pharmacological profiles to b oth DIDS and Rp-cAMPS, indicating that channels in addition to CFTR contrib ute to the low chloride response.