The major goal of this project is to understand how potassium ions are transported by epithelia. Two major epithelia which are responsible for the regulation of plasma potassium levels are the kidney and the colon. Studies of the rabbit descending colon are proposed as a model system for investigating K+ transport mechanisms. Specifically, the regulation of apical membrane Na+ and K+ permeabilities by a number of agents including aldosterone, cyclic nucleotides, and metabolic factors will be examined. Novel information will be obtained about basolateral membrane properties, specifically, K+ channels and their kinetic properties. Basolateral membrane K+ channels will also be assessed in toad bladder, Necturus gall bladder and locust rectal epithelium and compared to those from the colon. Regional differences in colonic K+ transport will be investigated and the mechanisms of Na+ and K+ transport in the human descending colon will be determined. The methods used to achieve these goals include: (1) conventional and ion-sensitive microelectrode techniques, (2) current-voltage relationships, (3) radio-isotopic flux determinations, (4) impedance analysis and morphometric measurement and (5) current fluctuation analysis. The information gained from these converging methods will be incorporated into an equivalent circuit model of the mammalian colon which takes into account morphological features, K+ channel properties and the regulation of K+ transport across the epithelium.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK029962-06
Application #
3229166
Study Section
Physiology Study Section (PHY)
Project Start
1981-07-01
Project End
1986-10-31
Budget Start
1986-07-01
Budget End
1986-10-31
Support Year
6
Fiscal Year
1986
Total Cost
Indirect Cost
Name
Yale University
Department
Type
Schools of Medicine
DUNS #
082359691
City
New Haven
State
CT
Country
United States
Zip Code
06520
Matsumoto, P S; Mo, L; Wills, N K (1997) Osmotic regulation of Na+ transport across A6 epithelium: interactions with prostaglandin E2 and cyclic AMP. J Membr Biol 160:27-38
Crowe, W E; Ehrenfeld, J; Brochiero, E et al. (1995) Apical membrane sodium and chloride entry during osmotic swelling of renal (A6) epithelial cells. J Membr Biol 144:81-91
Hagiya, M; Francavilla, A; Polimeno, L et al. (1994) Cloning and sequence analysis of the rat augmenter of liver regeneration (ALR) gene: expression of biologically active recombinant ALR and demonstration of tissue distribution. Proc Natl Acad Sci U S A 91:8142-6
Francavilla, A; Hagiya, M; Porter, K A et al. (1994) Augmenter of liver regeneration: its place in the universe of hepatic growth factors. Hepatology 20:747-57
Jovov, B; Lewis, S A; Crowe, W E et al. (1994) Role of intracellular Ca2+ in modulation of tight junction resistance in A6 cells. Am J Physiol 266:F775-84
Francavilla, A; Carr, B I; Azzarone, A et al. (1994) Hepatocyte proliferation and gene expression induced by triiodothyronine in vivo and in vitro. Hepatology 20:1237-41
Wills, N K; Purcell, R K; Clausen, C et al. (1993) Effects of aldosterone on the impedance properties of cultured renal amphibian epithelia. J Membr Biol 133:17-27
Wills, N K; Purcell, R K; Clausen, C (1992) Na+ transport and impedance properties of cultured renal (A6 and 2F3) epithelia. J Membr Biol 125:273-85
Yoshimi, F; Nakamura, K; Zhu, Y et al. (1991) Canine total orthotopic small bowel transplantation under FK 506. Transplant Proc 23:3240-2
Lewis, S A; Clausen, C; Wills, N K (1991) Transport-related modulation of the membrane properties of toad urinary bladder epithelium. Biochim Biophys Acta 1070:99-110

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