Membrane capacitance and conductance changes parallel mucin secretion in the human airway epithelium

1 Novartis Institutes for Biomedical Research, Horsham, West Sussex, United Kingdom; 2 Department of Physiology and Biophysics, Rosalind Franklin University of Medicine and Science, North Chicago, Illinois; and 3 Department of Pediatrics, University of Pittsburgh, Pittsburgh, Pennsylvania Submitted 11 August 2005 ; accepted in final form 5 October 2005 Measurement of the magnitude and kinetics of exocytosis from intact epithelia has historically been difficult. Using well-differentiated cultures of human bronchial epithelial cells, we describe the use of transepithelial impedance analysis to enable the real-time quantification of mucin secretagogue-induced changes in membrane capacitance (surface area) and conductance. ATP S, UTP, ionomycin, and PMA induced robust increases in total cellular capacitance that were demonstrated to be dominated by a specific increase in apical membrane surface area. The UTP-induced increase in capacitance occurred in parallel with goblet cell emptying and the secretion of mucin and was associated with decreases in apical and basolateral membrane resistances. The magnitude and kinetics of the capacitance increases were dependent on the agonist and the sidedness of the stimulation. The peak increase in capacitance induced by UTP was 30 mucin granule fusions per goblet cell. Secretagogue-induced decreases in apical membrane resistance were independent of exocytosis, although each of the secretagogues induced profound reductions in basolateral membrane resistance. Transepithelial impedance analysis offers the potential to study morphological and conductance changes in cultured human bronchial epithelial cells. degranulation; exocytosis; goblet cell; impedance analysis; mucus Address for reprint requests and other correspondence: J. L. Kreindler, Dept. of Pediatrics, Univ. of Pittsburgh, Pittsburgh, PA 15213 (e-mail: james.kreindler{at}chp.edu )