As a consequence of a broad spectrum of pathologic disorders, derangement in renal potassium excretion and subsequent alterations in extracellular potassium levels may have profound and even life-threatening effects on cell and organ function. Normally, potassium homeostasis is maintained largely through the regulation of unique, renal cortical collecting duct (CCD) K channels; the activity of these transport elements ultimately dictates the extent of urinary K excretion. To provide a rational framework for elucidating the defects in disorders of potassium homeostasis and designing more effective and specific treatments, it is essential to elucidate the molecular mechanisms governing the modulation of these channels. As the initial step in such an effort, l have recently employed an expression cloning strategy to isolate a novel K channel cDNA, we call CDK1, from a cortical collecting duct cell line. Based functional similarities between the CDK1 channel expressed in Xenopus oocytes and the native CCD K channel, the CDK1 cDNA is likely to encode the major- functional unit, the conductive-pore, of the cortical collecting duct secretory K channel. As a logical extension of these studies, a multidisciplinary approach combining electrophysiology, biochemistry and molecular biological techniques will be employed to l) address the hypothesis that CDK1 encodes the secretory K channel mediating urinary K excretion. 2) determine the molecular basis of the major avenues of short- term CCD K channel regulation and 3) determine the molecular basis for CCD K channel diversity. These studies represent a timely and important extension of the principal investigator's work, and should ultimately provide considerable insight into the basis of disorders in renal K handling and K homeostasis.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29DK048271-02
Application #
2148449
Study Section
General Medicine B Study Section (GMB)
Project Start
1994-08-01
Project End
1999-07-31
Budget Start
1995-08-01
Budget End
1996-07-31
Support Year
2
Fiscal Year
1995
Total Cost
Indirect Cost
Name
University of Maryland Baltimore
Department
Physiology
Type
Schools of Medicine
DUNS #
003255213
City
Baltimore
State
MD
Country
United States
Zip Code
21201
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Le Maout, S; Brejon, M; Olsen, O et al. (1997) Basolateral membrane targeting of a renal-epithelial inwardly rectifying potassium channel from the cortical collecting duct, CCD-IRK3, in MDCK cells. Proc Natl Acad Sci U S A 94:13329-34