Abstract

The cortical collecting duct (CCD) plays an important role in Na+ reabsorption and K+ excretion. Both K+ secretion and Na+ reabsorption involve several transport proteins including apical Na+ and K+ channels, Na-K-ATPase, and basolateral K+ channels. The basolateral K+ channels participate in generating cell membrane potential and play a critical role in K+ recycling which is important for maintaining the activity of the Na-K-ATPase. Preliminary experiments show that the basolateral small conductance K+ channel (SK) is involved in K+ recycling since the activity of the SK channels is closely related to the apical Na+ transport. That apical Na+ transport acts in concert with Na-K-ATPase and basolateral K+ conductance is important for maintaining a constant intracellular ion concentration and cell volume in the CCD. Therefore, the basolateral K+ channels must be regulated so that K+ recycling can match the apical Na+ transport. We have previously shown that the SK channels are activated by nitric oxide (NO) via a cGMP-dependent pathway. Furthermore, preliminary data demonstrated that inhibiting the apical Na+ transport reduces the activity of the basolateral SK channel activity and the effect of inhibiting Na+ transport depends on NO-cGMP signal transduction pathways. We propose to test the hypothesis that NO is critically involved in coupling the activity of the SK channels to the apical Na+ transport and the activity of Na-K-ATPase. The proposed studies have four Aims.
Aim 1 will involve investigating the effects of NO on the SK channels and exploring the mechanisms by which NO regulates the SK channels.
Aim 2 will study the role of NO in mediating the Ca2+ effects on the SK channels.
Aim 3 will assess the role of NO in mediating the coupling mechanism between apical Na+ transport and basolateral K+ channels and between Na-K-ATPase and basolateral K+ channels.
Aim 4 will examine the effect of Angiotensin II on the SK channel and investigate the role of NO in mediating the effect of angiotensin IL. Since the studies are conducted on freshly isolated CCD, the results will provide information essential for understanding the role of NO in the regulation of Na+ and K+ transport in the CCD.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
2R01DK047402-06
Application #
2693176
Study Section
General Medicine B Study Section (GMB)
Program Officer
Ketchum, Christian J
Project Start
1994-01-01
Project End
2003-12-31
Budget Start
1999-01-05
Budget End
1999-12-31
Support Year
6
Fiscal Year
1999
Total Cost
Indirect Cost

  Institution

Name
New York Medical College
Department
Pharmacology
Type
Schools of Medicine
DUNS #
City
Valhalla
State
NY
Country
United States
Zip Code
10595

  Publications

Wei, Yuan; Liao, Yi; Zavilowitz, Beth et al. (2014) Angiotensin II type 2 receptor regulates ROMK-like K? channel activity in the renal cortical collecting duct during high dietary K? adaptation. Am J Physiol Renal Physiol 307:F833-43
Jin, Yan; Wang, Yan; Wang, Zhi-Jian et al. (2009) Inhibition of angiotensin type 1 receptor impairs renal ability of K conservation in response to K restriction. Am J Physiol Renal Physiol 296:F1179-84
Wang, Wen-Hui; Giebisch, Gerhard (2009) Regulation of potassium (K) handling in the renal collecting duct. Pflugers Arch 458:157-68
Muto, Shigeaki; Tsuruoka, Shuichi; Miyata, Yukio et al. (2009) Basolateral Na+/H+ exchange maintains potassium secretion during diminished sodium transport in the rabbit cortical collecting duct. Kidney Int 75:25-30
Wei, Yuan; Zavilowitz, Beth; Satlin, Lisa M et al. (2007) Angiotensin II inhibits the ROMK-like small conductance K channel in renal cortical collecting duct during dietary potassium restriction. J Biol Chem 282:6455-62
Babilonia, Elisa; Li, Dimin; Wang, Zhijian et al. (2006) Mitogen-activated protein kinases inhibit the ROMK (Kir 1.1)-like small conductance K channels in the cortical collecting duct. J Am Soc Nephrol 17:2687-96
Babilonia, Elisa; Wei, Yuan; Sterling, Hyacinth et al. (2005) Superoxide anions are involved in mediating the effect of low K intake on c-Src expression and renal K secretion in the cortical collecting duct. J Biol Chem 280:10790-6
Sterling, Hyacinth; Lin, Dao-Hong; Chen, Yu-Jung et al. (2004) PKC expression is regulated by dietary K intake and mediates internalization of SK channels in the CCD. Am J Physiol Renal Physiol 286:F1072-8
Lin, Dao-Hong; Sterling, Hyacinth; Yang, Baofeng et al. (2004) Protein tyrosine kinase is expressed and regulates ROMK1 location in the cortical collecting duct. Am J Physiol Renal Physiol 286:F881-92
Sterling, Hyacinth; Lin, Dao-Hong; Gu, Rui-Min et al. (2002) Inhibition of protein-tyrosine phosphatase stimulates the dynamin-dependent endocytosis of ROMK1. J Biol Chem 277:4317-23

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