It is well known that the kidney plays a critical role in maintaining extracellular fluid composition and volume. This role is essential for human life. The kidney functions by employing three processes: filtration of large quantities of ultra filtrate across the glomerular filtration barrier; reabsorption of most of the solutes and water; and secretion of certain key substances such as K+, H+, and organic solutes. It is abundantly clear that conductive movement of ions across renal cell membranes plays a key role in solute reabsorption and secretion and in volume regulation. They key focus of this budget period is on the biophysics, regulation, and molecular biology of conductive Ca2+, and K+ movement in the kidney. A model CA+2-activated K+ channel regulation has emerged from more previous studies. This work will be extended to determine the role of calmodulin and protein kinase in regulating these channels. In addition, the role of CA2+ channels and intracellular Ca2+ in regulating CA+2-activated K+ channels will be explored. The properties and regulation of CA +2-activated K+ channels and Ca2+ channels will be studies using single channel patch clamping experiments. The molecular biology of + and Ca2+ channels in the kidney will also be studied. The specific approach is: to determine the cDNA sequence of K+ and Ca2+ channels by cloning either by homology to known channel sequences or by oocyte expression; to determine the properties of renal K+ and Ca2+ channels expressed in Xenopus oocytes; to generate polyclonal antibodies against specific sequences in the channel molecule; to determine the tissue localization of the channels and to assess the role of these channels in renal function. This an important approach because it will provide information at several levels: the molecular structure; nephron localization and function of these channels. Information provided these studies on channel function and molecular biology will be instrumental in increasing our knowledge how solute secretion and absorption occurs normally in the kidney and how renal cells control their volume. It may also will help to increase our knowledge of diseases such as hypertension.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37DK032753-15
Application #
2443960
Study Section
Special Emphasis Panel (NSS)
Project Start
1983-07-01
Project End
1999-06-30
Budget Start
1997-07-01
Budget End
1998-06-30
Support Year
15
Fiscal Year
1997
Total Cost
Indirect Cost
Name
Johns Hopkins University
Department
Physiology
Type
Schools of Medicine
DUNS #
045911138
City
Baltimore
State
MD
Country
United States
Zip Code
21218
de Lemos Barbosa, Carolina Monteiro; Souza-Menezes, Jackson; Amaral, Andressa Godoy et al. (2016) Regulation of CFTR Expression and Arginine Vasopressin Activity Are Dependent on Polycystin-1 in Kidney-Derived Cells. Cell Physiol Biochem 38:28-39
Peruchetti, Diogo B; Cheng, Jie; Caruso-Neves, Celso et al. (2014) Mis-regulation of mammalian target of rapamycin (mTOR) complexes induced by albuminuria in proximal tubules. J Biol Chem 289:16790-801
Tin, Adrienne; Woodward, Owen M; Kao, Wen Hong Linda et al. (2011) Genome-wide association study for serum urate concentrations and gout among African Americans identifies genomic risk loci and a novel URAT1 loss-of-function allele. Hum Mol Genet 20:4056-68
Santoso, Netty G; Cebotaru, Liudmila; Guggino, William B (2011) Polycystin-1, 2, and STIM1 interact with IP(3)R to modulate ER Ca release through the PI3K/Akt pathway. Cell Physiol Biochem 27:715-26
Woodward, Owen M; Köttgen, Anna; Köttgen, Michael (2011) ABCG transporters and disease. FEBS J 278:3215-25
Woodward, Owen M; Li, Yun; Yu, Shengqiang et al. (2010) Identification of a polycystin-1 cleavage product, P100, that regulates store operated Ca entry through interactions with STIM1. PLoS One 5:e12305
Kwon, Young; Kim, Sang Hoon; Ronderos, David S et al. (2010) Drosophila TRPA1 channel is required to avoid the naturally occurring insect repellent citronellal. Curr Biol 20:1672-8
Guggino, Sandra E (2009) Can we generate new hypotheses about Dent's disease from gene analysis of a mouse model? Exp Physiol 94:191-6
Wright, Jerry; Morales, Marcelo M; Sousa-Menzes, Jackson et al. (2008) Transcriptional adaptation to Clcn5 knockout in proximal tubules of mouse kidney. Physiol Genomics 33:341-54
Guggino, Sandra E (2007) Mechanisms of disease: what can mouse models tell us about the molecular processes underlying Dent disease? Nat Clin Pract Nephrol 3:449-55

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