Effects of Calcium on Intestinal Mucin: Implications for Cystic Fibrosis

Abstract

Extract: A major feature of the disease cystic fibrosis is the excessive concentration of mucus within ducts and glands of mucous-producing organs. Some mucous secretions also show an elevation in calcium concentration. Using purified rat intestinal goblet cell mucin as a model mucin, we have investigated the effect of millimolar additions (1–25 mM ) of CaCl₂ on the physical properties of the mucin. Isotonicity of incubation media was preserved in order to mimic in vivo conditions. CaCl₂ (8–15 mM) caused a 15–33% decrease in viscosity, no change in electrophoretic mobility in acrylamide gels, and a 20–30% decrease in solubility of the mucin. Solubility changes were reversed by the addition of EDTA (20 mM ) to incubations. Insolubility was also produced in incubations of mucin with a mixture of soluble intestinal contents (NaCl washings). These findings strongly suggest that the mucin became smaller and more dense as calcium was added, a process most probably achieved by loss of intramolecular water. Speculation: It is hypothesized that elevated concentrations of calcium within glycoprotein secretions of patient with cystic fibrosis may substantially increase the density and insolubility of mucins, promoting the formation of mucous “plugs.”