The central goal of this project is to characterize the mechanisms of regulation of the four cellular transport processes involved in net Cl movement across secretory epithelia. At the basolateral membrane, these include NaCl co-transport mechanisms, Na/K pumps, and K channels; and, at the apical membrane, Cl channels. The effects of cAMP- and Ca-dependent agonists will be evaluated by monitoring ionic currents and transepithelial fluxes across polyene-treated tissues and by application of conventional and ion-selective microelectrode and patch clamp techniques to isolated tracheal epithelium, primary tracheal cell cultures and colonic tumor cell cultures. The effects of cAMP- and Ca-dependent intracellular regulatory systems (e.g. protein kinases) on Cl and K conductances and channel kinetics will also be examined. Secretagogue-induced cell volume alterations and the role of volume regulation in the concerted response to secretory agonists will be determined. Finally, we will evaluate the cellular basis for dual regulation of NaCl co-transport and K conductance in two absorptive epithelia whose transport processes resemble those found in secretory tissues. Our studies will provide a complete characterization of the mechanisms underlyng cAMP- and Ca-dependent regulation and permit construction of a dynamic model of the events involved in stimulation of Cl-secreting epthelia.
| Frizzell, R A; Halm, D R; Rechkemmer, G et al. (1986) Chloride channel regulation in secretory epithelia. Fed Proc 45:2727-31 |
| Frizzell, R A; Rechkemmer, G; Shoemaker, R L (1986) Altered regulation of airway epithelial cell chloride channels in cystic fibrosis. Science 233:558-60 |
| Halm, D R; Frizzell, R A (1986) Active K transport across rabbit distal colon: relation to Na absorption and Cl secretion. Am J Physiol 251:C252-67 |
| Shoemaker, R L; Frizzell, R A; Dwyer, T M et al. (1986) Single chloride channel currents from canine tracheal epithelial cells. Biochim Biophys Acta 858:235-42 |
| Halm, D R; Krasny Jr, E J; Frizzell, R A (1985) Electrophysiology of flounder intestinal mucosa. I. Conductance properties of the cellular and paracellular pathways. J Gen Physiol 85:843-64 |
| Halm, D R; Krasny Jr, E J; Frizzell, R A (1985) Electrophysiology of flounder intestinal mucosa. II. Relation of the electrical potential profile to coupled NaCl absorption. J Gen Physiol 85:865-83 |
