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The impact of small anions on the physical properties of gel-forming mucin has been almost overlooked relative to that of cations. Recently, based on the coincident abnormalities in HCO(3)(-) secretion and abnormal mucus formed in the hereditary disease, Cystic Fibrosis (CF), HCO(3)(-) was hypothesized to be critical in the formation of normal mucus by virtue of its ability to sequester Ca(2+) from condensed mucins being discharged from cells. However, direct evidence of the impact of HCO(3)(-) on mucus properties is lacking. Herein, we demonstrate for the first time that mucin diffusivity (~1/viscosity) increases as a function of [HCO(3)(-)]. Direct measurements of exocytosed mucin swelling kinetics from airway cells showed that mucin diffusivity increases by ~300 percent with 20 mM extracellular HCO(3)(-) concentration. Supporting data indicate that HCO(3)(-) reduces free Ca(2+) concentration and decreases the amount of Ca(2+) that remains associated with mucins. The results demonstrate that HCO(3)(-) enhances mucin swelling and hydration by reducing Ca(2+) cross-linking in mucins, thereby decreasing its viscosity and likely increasing its transportability. In addition, HCO(3)(-) can function as a Ca(2+) chelator like EGTA (ethylene glycol tetraacetic acid) to disperse mucin aggregates. This study indicates that poor HCO(3)(-) availability in CF may explain why secreted mucus remains aggregated and more viscous in affected organs. These insights bear not only the fundamental pathogenesis in CF, but also on the process of gel mucus formation and release in general.
1University of California Merced.
This article was published in the following journal.
Name: American journal of physiology. Lung cellular and molecular physiology
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Membrane proteins that allow the exchange of chloride ions for bicarbonate ions across the cellular membrane. The action of specific antiporters in this class serve important functions such as allowing the efficient exchange of bicarbonate across red blood cell membranes as they passage through capillaries and the reabsorption of bicarbonate ions by the kidney.
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