A New Role for Bicarbonate in Mucus Formation.

14:55 EDT 2nd September 2014 | BioPortfolio

Summary of "A New Role for Bicarbonate in Mucus Formation."

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.

Affiliation

1University of California Merced.

Journal Details

This article was published in the following journal.

Name: American journal of physiology. Lung cellular and molecular physiology
ISSN: 1522-1504
Pages:

Links

PubMed Articles [14545 Associated PubMed Articles listed on BioPortfolio]

Dynamic Changes in Mucus Thickness and Ion Secretion during Citrobacter rodentium Infection and Clearance.

Citrobacter rodentium is an attaching and effacing pathogen used as a murine model for enteropathogenic Escherichia coli. The mucus layers are a complex matrix of molecules, and mucus swelling, hydrat...

Rates of synthesis and source of glycolate in intact chloroplasts.

Intact chloroplasts capable of high rates of CO2 assimilation completely oxidized 3-phosphoglycerate and dihydroxyacetone phosphate to glycolate when CO2 concentrations were low. Bicarbonate was conve...

Role of the bicarbonate-responsive soluble adenylyl cyclase in pH sensing and metabolic regulation.

The evolutionarily conserved soluble adenylyl cyclase (sAC, adcy10) was recently identified as a unique source of cAMP in the cytoplasm and the nucleus. Its activity is regulated by bicarbonate and fi...

Attenuation of cigarette smoke-induced airway mucus production by hydrogen-rich saline in rats.

Over-production of mucus is an important pathophysiological feature in chronic airway disease such as chronic obstructive pulmonary disease (COPD) and asthma. Cigarette smoking (CS) is the leading cau...

Spontaneous Colitis in Muc2-Deficient Mice Reflects Clinical and Cellular Features of Active Ulcerative Colitis.

The colonic mucus layer plays a critical role in intestinal homeostasis by limiting contact between luminal bacteria and the mucosal immune system. A defective mucus barrier in animal models allows ba...

Clinical Trials [1285 Associated Clinical Trials listed on BioPortfolio]

Inhaled Bicarbonate Therapy in Cystic Fibrosis

The purpose of this study is to see if inhaled bicarbonate will increase the ability to cough up mucus in a person with cystic fibrosis.

Effect of Potassium Bicarbonate Supplementation on Bone and Muscle in Older Adults

There is increasing evidence that the acid-base balance of diet plays an important role in the health of bones and muscles. An excess of acid in the body can result in calcium loss and mus...

Oral Versus Intravenous Hydration to Prevent Contrast Induced Nephropathy

The increased risk for contrast-induced nephropathy (CIN) in patients with chronic kidney disease (CKD) undergoing coronary angiography (CAG) has been established. Current and historical ...

Effect of Lucinactant on Mucus Clearance in Cystic Fibrosis Lung Disease

Mucus clearance is impaired in cystic fibrosis. Inhaled surfactants may reduce adhesive forces between mucus and airway surfaces and improve mucus clearance. This in turn my improve lung...

Use of Bicarbonate to Reduce the Incidence of Acute Renal Failure After Cardiac Surgery

The purpose of this study is to determine if the incidence of acute renal failure (ARF) in high risk patients who undergo coronary artery bypass grafting (CABG) is reduced by treating pati...

Medical and Biotech [MESH] Definitions

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.

The liquid secretion of the stomach mucosa consisting of hydrochloric acid (GASTRIC ACID); PEPSINOGENS; INTRINSIC FACTOR; GASTRIN; MUCUS; and the bicarbonate ion (BICARBONATES). (From Best & Taylor's Physiological Basis of Medical Practice, 12th ed, p651)

Proteins that cotransport sodium ions and bicarbonate ions across cellular membranes.

A bone morphogenetic protein that may play a role in CARTILAGE formation. It is a potent regulator of the growth of CHONDROCYTES and the synthesis of cartilage matrix proteins. Evidence for its role in cartilage formation can be seen in MICE, where genetic mutations that cause loss of bone morphogenetic protein 5 function result in the formation of small malformed ears.

A synthetic methylprostaglandin E1 analog that reduces gastric acid secretion and enhances the gastric mucus-bicarbonate barrier. It is effective in the therapy of gastric ulcers and gives significant protection against NSAID-induced gastric mucosal damage. The drug also prevents cyclosporin A-induced damage to endocrine and exocrine pancreatic secretions. It shows a low order of acute toxicity and there is no evidence of embryotoxicity, fetotoxicity, teratogenicity, or mutagenicity in animal studies.

Search BioPortfolio: