Our long term goal is to characterize the mechanisms involved in the regulation of ion transport in tight epithelia. One immediate aim is to analyze the mechanisms that regulate K+ movements across apical and basolateral membranes. It is becoming clear that elucidation of the regulation of K+ conductance is necessary for a full understanding of the signals involved in regulating transepithelial ion transport. We are examining the response of basolateral K+ conductance to increases in cell cyclic AMP induced directly by the addition of cAMP analogs or by neurohypophysial hormones. We are also interested in the modulations of basolateral membrane K+ conductance that occur when transepithelial Na+ transport is either stimulated or inhibited by mechanisms that presumably do not involve changes in cAMP levels. We intend to use conventional microelectrode and fluctuation analysis techniques, as well as the patch clamp technique, to characterize the properties of different K+ pathways. This approach will allow us to determine the relationship between the behavior observed in the whole tissue and that of the isolated channel. By comparing the properties of apical and basolateral K+ pathways we will examine whether or not the same channel is located in both membranes. Another major aim is to study the properties of a cAMP activated, Ca2+-sensitive, monovalent-cation selective channel that we have identified in the apical membrane of the toad urinary bladder and skin. We will examine whether this is a channel akin to the divalent cation channels of excitable tissues and what its role is in the response of epithelia to agents that increase cAMP. Finally, we intend to continue examining the mechanism of the stimulation of Na+ transport caused by hypotonic solutions. This is important because cell volume may be one of the signals involved in adjusting basolateral conductance to changes in ionic flux through the basolateral membrane, and because changes in cell volume trigger volume regulatory responses in cells. We are particularly interested in determining whether hypotonic solutions stimulate cAMP synthesis in the epithelium and the characteristics of their activation of the apical Na+ channel.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK033612-06
Application #
3232025
Study Section
General Medicine B Study Section (GMB)
Project Start
1984-04-01
Project End
1992-03-31
Budget Start
1989-04-01
Budget End
1990-03-31
Support Year
6
Fiscal Year
1989
Total Cost
Indirect Cost
Name
Suny Downstate Medical Center
Department
Type
Schools of Medicine
DUNS #
068552207
City
Brooklyn
State
NY
Country
United States
Zip Code
11203
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Erlij, D; De Smet, P; Van Driessche, W (1994) Effect of insulin on area and Na+ channel density of apical membrane of cultured toad kidney cells. J Physiol 481 ( Pt 3):533-42
Escalante, B; Erlij, D; Falck, J R et al. (1993) Cytochrome P450-dependent arachidonate metabolites affect renal transport in the rabbit. J Cardiovasc Pharmacol 22 Suppl 2:S106-8
Erlij, D; Kaufman, A I; Gersten, L (1992) Urinary Ca2+ and the regulation of K+ secretion in toad bladder by neurohypophyseal hormones. Pflugers Arch 420:23-8
Escalante, B; Erlij, D; Falck, J R et al. (1991) Effect of cytochrome P450 arachidonate metabolites on ion transport in rabbit kidney loop of Henle. Science 251:799-802
Escalante, B; Erlij, D; Falck, J R et al. (1991) Ion transport inhibition in the medullary thick ascending limb of Henle's loop by cytochrome P450-arachidonic acid metabolites. Adv Prostaglandin Thromboxane Leukot Res 21A:209-12
Thompson, J S; Bragg, L E; Saxena, S K (1990) The effect of intestinal resection and urogastrone on intestinal regeneration. Arch Surg 125:1617-21
Reinach, P S; Schoen, H F (1990) NPPB inhibits the basolateral membrane K+ conductance in the isolated bullfrog cornea. Biochim Biophys Acta 1026:13-20
Schoen, H F (1989) Secretagogues increase apical membrane conductance of isolated bullfrog corneal epithelium pretreated with loop diuretics. Pflugers Arch 414:713-8
Schoen, H F; Kaufman, A; Erlij, D (1988) Effects of oxytocin on cation content and electrophysiology of frog skin epithelium. Am J Physiol 255:C357-67