By virtue of asymmetric distributions of ionic channels and pump mechanisms in apical and basolateral membranes of epithelial cells, epithelial tissues of renal and other origin regulate the composition of body fluids. In order to obtain a better understanding of the mechanisms involved, methods of fluctuation or noise analysis are to be used that allow the electrodiffusive Na+ channel densities and single channel Na+ currents to be measured at the apical membranes of the cells. In this way, the ? possible mechanisms whereby ionic permeability is regulated will be investigated with special emphasis on the phenomenon of """"""""autoregulation"""""""" whereby Na+ channel density appears to change in compensatory fashion in response to procedures that inhibit Na+ entry into the cells. In complementary fashion, methods of patch clamp will be used to study the apical membranes of renal tubule cells to obtain direct information of the unitary currents and their kinetics under various physiological conditions (mineralocorticoids, ADH) known to alter Na+ absorption and K+ secretion.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK030824-08
Application #
3229673
Study Section
Physiology Study Section (PHY)
Project Start
1982-04-01
Project End
1991-03-31
Budget Start
1989-04-01
Budget End
1991-03-31
Support Year
8
Fiscal Year
1989
Total Cost
Indirect Cost
Name
University of Illinois Urbana-Champaign
Department
Type
Schools of Arts and Sciences
DUNS #
041544081
City
Champaign
State
IL
Country
United States
Zip Code
61820
Paunescu, T G; Helman, S I (2001) cAmp activation of apical membrane Cl(-) channels: theoretical considerations for impedance analysis. Biophys J 81:838-51
Paunescu, T G; Helman, S I (2001) PGE(2) activation of apical membrane Cl(-) channels in A6 epithelia: impedance analysis. Biophys J 81:852-66
Butterworth, M B; Helman, S I; Els, W J (2001) cAMP-sensitive endocytic trafficking in A6 epithelia. Am J Physiol Cell Physiol 280:C752-62
Paunescu, T G; Blazer-Yost, B L; Vlahos, C J et al. (2000) LY-294002-inhibitable PI 3-kinase and regulation of baseline rates of Na(+) transport in A6 epithelia. Am J Physiol Cell Physiol 279:C236-47
Awayda, M S; Van Driessche, W; Helman, S I (1999) Frequency-dependent capacitance of the apical membrane of frog skin: dielectric relaxation processes. Biophys J 76:219-32
Helman, S I; Liu, X; Baldwin, K et al. (1998) Time-dependent stimulation by aldosterone of blocker-sensitive ENaCs in A6 epithelia. Am J Physiol 274:C947-57
Blazer-Yost, B L; Liu, X; Helman, S I (1998) Hormonal regulation of ENaCs: insulin and aldosterone. Am J Physiol 274:C1373-9
Els, W J; Liu, X; Helman, S I (1998) Differential effects of phorbol ester (PMA) on blocker-sensitive ENaCs of frog skin and A6 epithelia. Am J Physiol 275:C120-9
Helman, S I; Liu, X (1997) Substrate-dependent expression of Na+ transport and shunt conductance in A6 epithelia. Am J Physiol 273:C434-41
Blazer-Yost, B L; Helman, S I (1997) The amiloride-sensitive epithelial Na+ channel: binding sites and channel densities. Am J Physiol 272:C761-9

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