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Molecular mechanisms of renal tubular electrolyte
transport.
Our research is concerned with cellular and
molecular mechanisms of solute and solvent transport in the kidney.
We are studying single renal tubules, in order to obtain quantitative
information about the driving forces acting on Na+, Cl-, K+, HCO3- and
H+ -ions as they traverse the luminal and antiluminal cell membranes
of the tubular epithelium.
Techniques we are now applying to single tubules
include free-flow micropuncture, microperfusion of defined tubular segments,
electron microscopy, and several electrophysiological methods: intracellular
voltage measurements, cell ion activity measurements, patch-clamping
and cell fluorescence measurements (pH, Ca, Na, etc) are also employed.
Specific problems being addressed include the mechanism of chloride
transport across proximal tubular epithelium; the mechanism of solute-solvent
coupling; the relationship between cell Na+ activity, metabolism and
net fluid transport in single nephrons; and the relationship among cell
Ca++ activity, cell pH, and cell Na+/K+ during regulation of sodium
transport. We have also investigated in detail the cell mechanism of
renal potassium transport and are studying single channel behavior in
vivo as well as the function of cloned K channels expressed in oocytes.
 Figure
caption:
Effect of changes of cytosolic pH on activity
of low conductance potassium channel in the apical membrane of a principal
tubule cell of the rat kidney. Experiments were carried out in excised
inside-out patches in which pH was varied. C: zero current flow. Note
the presence of two channels at pH 7.4, their dramatic suppression at
pH 7.O and their reappearance with restoration of pH 7.4.
Recent publications:
Giebisch
G. Renal
potassium channels: Function, regulation, and structure. Kidney
Int. 2001 Aug;60(2):436-45.
Knauf F, Yang CL, Thomson RB, Mentone SA, Giebisch G, Aronson PS. Identification
of a chloride-formate exchanger expressed on the brush border membrane
of renal proximal tubule cells. Proc Natl Acad Sci U S A. 2001 Jul
31;98(16):9425-30.
Wang T, Yang CL, Abbiati T, Shull GE, Giebisch G, Aronson PS. Essential
role of NHE3 in facilitating formate-dependent NaCl absorption in the
proximal tubule. Am J Physiol Renal Physiol. 2001 Aug;281(2):F288-92.
Eickelberg O, Geibel J, Seebach F, Giebisch G, Kashgarian M. K+-induced
HSP-72 expression is mediated via rapid Ca2+ influx in renal epithelial
cells. Am J Physiol Renal Physiol. 2001 Aug;281(2):F280-7.
gerhard.giebisch@yale.edu
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