Soda stream modifies airway fluid

Figure 1. The contribution of the newly described paracellular HCO3 conductance to airway surface liquid (ASL) secretion by epithelia In health, cystic-fibrosis transmembrane-regulator (CFTR) together with pendrin and other anion channels (not shown) extrude Cl– and HCO3 across the apical membrane of these cells, creating a transepithelial electrochemical gradient that draws Na+ through the cation-selective paracellular pathway, ultimately generating a transepithelial osmotic gradient that draws water from the pulmonary interstitial fluid onto the airway surface. The volume of periciliary fluid (the aqueous component of ASL) is fine-tuned by the balancing action of the epithelial Na+ channel (ENaC) which reabsorbs Na+, perhaps in concert with paracellular Cl– reabsorption, tempering net fluid secretion. Basolateral processes are omitted for simplicity, but include Na+-coupled transporters for importing Cl– and HCO3 (or extruding H+, the by-product of intracellular HCO3 generation by carbonic anhydrase). The importance of transcellular ion transport for appropriate periciliary fluid secretion is evident from the pulmonary disease in patients with inactivating mutations in CFTR (i.e., cystic fibrosis) or hyperactivating mutations in ENaC. The influence of CFTR-mediated HCO3 secretion on periciliary fluid pH is tempered by channel and pump-mediated H+ secretion (Fischer & Widdicombe, 2006). Under these conditions, the newly described paracellular HCO3 flux (red) would tend to counter ASL alkalinization (A). Should the ASL become acidic as, for example, in newborns with cystic fibrosis, this paracellular HCO3 flux would reverse and tend to be counter ASL acidification (B). vehicle for their expulsion by tract-lining cilia that move the mucus out towards the throat (mucociliary clearance). The periciliary fluid beneath hydrates the mucus, provides a largely mucus-free zone in which the cilia can beat, acts as a lubricant between the mucus and the tract wall, and contains a number of antimicrobial factors (Fahy & Dickey, 2010). A critical parameter of ASL is its bicarbonate concentration ([HCO3]) which, by limiting ASL acidification, lowers mucus viscosity and promotes the efficacy of local pathogen defense systems (Shin et al. 2020). Indeed, acidic ASL is an exacerbating feature of several lung diseases (e.g. asthma, cystic fibrosis: Hunt & Gaston, 2013), and airway alkalinization has emerged as a promising therapeutic strategy (Alaiwa et al. 2016; Delpiano et al. 2018). In their paper in the current issue of The Journal of Physiology, Thornell et al. (2020) expand our knowledge of the mechanisms that control periciliary, and therefore ASL, [HCO3] and pH. Periciliary fluid is secreted by surface epithelial cells that line the conducting passages as well as by acinar cells in the submucosal glands that drain into these passages. The importance of transcellular and paracellular ion fluxes for this process are well documented (Fig. 1A). Although the tight junctions are predominantly cation selective, they are also permeable to anions. A paracellular HCO3 flux has been mooted to balance ASL pH defects (e.g. in children with cystic fibrosis) but its existence has never been demonstrated (Fischer & Widdicombe, 2006; Schultz et al. 2017). In their paper, Thornell et al. (2020) investigate whether the paracellular pathway