The cells of epithelia, of renal and other origin, are responsible for the vectorial transport of salt and water between the fluids bathing the apical and basolateral membranes of the cells. Being sensitive to hormonal and pharmacological influences, epithelia regulate and participate in the homeostatic mechanisms that maintain the fluid environments of an organism. Whereas """"""""tight"""""""" epithelia like the distal tubules of the kidney and the frog skin actively transport Na ions from apical to basolateral fluids, the mechanisms and the control of the mechanisms of a) apical membrane permeability to Na and other ions, b) the metabolically dependent Na/K exchange pumps at the basolateral membranes, and c) the passive ionic transport processes of the basolateral membranes are not well understood. To investigate these, studies are to be done electrophysiologically and isotopically with isolated epithelia of frog skin that permit investigations of the basolateral membranes in the relative absence of important unstirred layers. Electrophysiological and isotopic fluxes are designed to examine the nature of the Na/K exchange pump and its stoichiometry under changing conditions of transepithelial Na transport, and especially under conditions where intracellular pH and ionized Ca++ are believed to exert important influences on the membranes. Nuclear magnetic resonance spectroscopy is to be done to examine the intracellular pH and phosphorous metabolites that relate directly to the energy supply of the pumps and other metabolically dependent processes of the cell membranes. To study apical membranes directly, and the nature and control of their Na and K channels, patch clamp studies are proposed in renal epithelia that will permit access to data not available by other means.
| Baxendale-Cox, L M; Duncan, R L; Liu, X et al. (1997) Steroid hormone-dependent expression of blocker-sensitive ENaCs in apical membranes of A6 epithelia. Am J Physiol 273:C1650-6 |
| Helman, S I; Baxendale, L M (1990) Blocker-related changes of channel density. Analysis of a three-state model for apical Na channels of frog skin. J Gen Physiol 95:647-78 |
