Schematic of laboratory set up for potential difference (PD) measurements in ferrets.

Cartoon representing hardware and electrical connections representing PD apparatus modified from the human instrument recommended by the standard operating procedure of the CF Therapeutics Development Network and the European Clinical Trial Network [19]. Ground Lead: Connects electrical apparatus to ground for reference from which voltage is measured. Headstage: Connects electrode inputs to bioamplifier and safely isolates from wall AC current. Bioamplifier: Serves as voltmeter to measure PD. Analog-Digital Converter: Converts analog signals to digital form. K/Cl Calomel Electrodes: Measure PD. Agar Bridge: Connects positively charged (+) calomel electrodes to ferret nasal epithelium or lower airway epithelium through Airway Catheter and negatively charged (-) calomel electrodes to subcutaneous tissue through Butterfly Needle. Syringe Pumps: Deliver test solutions perfused sequentially from pump 1 to 5 with a flow rate of 4ml/hr (see S1 Table). The PD changes are observed and recorded on the computer using LabChart 7.0 software. Following the procedure, the nasal cannula and subcutaneous needle were removed, and anesthesia reversed with atipamezole (5 mg/kg body weight, IM) delivered at an equal volume as dexmedetomidine. All ferrets recovered within 10–15 min, and remained on a warming pad until aroused and moving. Supplemental oxygen was not required during the NPD procedures in our experience, however supplemental oxygen was delivered during recovery from anesthesia.