Airway Surface Liquid Calcium Modulates Chloride Permeability in the Cystic Fibrosis Airway

Abstract

Patients with cystic fibrosis (CF) demonstrate a characteristic defect in epithelial chloride movement, which can be demonstrated in vivo by the nasal potential difference technique. After amiloride pretreatment, the CF airway exhibits only a transient response to perfusion with low-chloride solution, contrasting with the sustained hyperpolarization seen in control subjects. This study further investigated the response to low-chloride solution in the CF airway, examining the interaction between surface divalent ions and the low-chloride response. Sequential perfusion with amiloride, low chloride, and isoproterenol was tested in groups of subjects with CF, with the diluent containing different concentrations of calcium and magnesium, on different days. When the low-chloride response was measured with the nominally calcium-free diluents, the subjects with CF had mean (SEM) responses of 8.0 (0.7), 8.6 (2.4), and 9.6 (1.6) mV in the presence of 0, 1, and 3 mM Mg2+, respectively, significantly different from the response in the presence of divalent ions. However, the subsequent response to isoproterenol was not different in the presence or absence of divalent ions. We hypothesize that perfusion of the CF airway with nominally calcium-free solutions reduces tonic inhibition of chloride secretion.

Hypertonic saline inhibits luminal sodium channels in respiratory epithelium

“…There are two possible explanations for the relatively large change in PD associated with a reduction in luminal Cl ¡ concentration in CF: (1) The solutions used in our study to superfuse the respiratory epithelium did not contain Ca 2+ and Mg 2+ . It has been shown that solutions lacking these divalent ions lead to a larger change in PD associated with a reduction in luminal Cl ¡ concentration compared with solutions containing Ca 2+ and Mg 2+ (Middleton et al 2003). This eVect might result from an increase in the open probability of tight junctions induced by a reduction in extracellular Ca 2+ concentration (Gorodeski et al 1997), thereby promoting Cl ¡ Xux to the luminal side of the epithelium if apical Cl ¡ concentration is low.…”

Impact of different chloride and glucose solutions on nasal potential difference

“…Nasal PD was measured using previously described methods. 3,12,13 Briefly, the exploring electrode consisted of a double lumen silicone rubber tube with the openings of both lumens at the same site, 3 mm from the tip. One lumen was filled with an equal mixture of saline and ECG electrode cream, connected to a high impedance voltmeter via a silver/silver chloride electrode.…”

Measurement of airway ion transport assists the diagnosis of cystic fibrosis

“…The nasal PD test provides important information to assist in the diagnosis of CF, especially in cases where the sweat test and genotype analysis are non‐diagnostic 5. The nasal PD has been used to assess the epithelial effects of current treatments 6, 7, to test the efficacy of potential new drugs for CF 8, 9, and also to investigate the physiology of the ion transport defects in CF 10, 11.…”