• Dawson, David (PI)

Project: Research project

Project Details


The sodium and potassium content of human body fluids is maintained through
active absorption or secretion of these ions by epithelial tissues like the
colon and distal renal tubule. Alterations in electrolyte balance brought
about by circulating hormones, pathological states, or drugs reflect the
actions of these agents on specific transport processes in the apical and
basolateral membranes of epithelial cells. In order to understand the
cellular mechanisms underlying epithelial transport and its regulation it
is necessary to employ model systems which may be isolated from the
organism and studied under conditions where the driving forces for mass
transport can be readily manipulated. In addition it is essential to
develop methods which permit the individual properties of apical and
basolateral membranes to be discerned. The object of the proposed research
is to identify the ion transport elements in the apical and basolateral
membranes of epithelial cells, to investigate the mechanism of ion
translocation through these elements, and to determine what cellular
factors regulate ion traffic through specific elements. We will employ two
model systems, the large intestine of the turtle and the urinary bladder of
the winter flounder, which may be conveniently studied in vitro. We will
employ techniques which enable us to "functionally isolate" individual
transport elements in the intact epithelium so that their properties may be
studied directly using electrophysiological and radioisotope techniques
which are well established in our laboratory. We will attempt to develop a
preparation of isolated colonic cells which will permit us to study the
relation between plasma membrane transport and cell composition. In
addition we will attempt to isolate plasma membrane fractions which are
enriched in apical and basolateral membranes so that transport elements can
be isolated in membrane vesicles and, ultimately, reconstituted in
liposomes or lipid bilayers. This three-pronged approach will enable us to
trace the properties of individual transport elements through successive
stages of purification and ultimately to obtain an integrated description
of the cellular transport of sodium and potassium and the regulation of
these processes under normal conditions as well as in pathologic states.
Effective start/end date5/1/812/28/87


  • National Institutes of Health


  • Medicine(all)


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