Our research project will focus on the exploration of unresolved problems concerning the regulation of renal potassium (K+) channels (ROMK). The kidney plays a major role in potassium homeostasis by a balance between potassium secretion in principal tubule cells and potassium reabsorption in intercalated cells of the distal nephron. Following active uptake of potassium across the basolateral membrane by Na-K+ ATPase, diffusion across the apical membrane of principal cells occurs via low-conductance potassium channels. These channels have been cloned and we propose to explore the mechanism of their regulation. Two major goals will be pursued. First, we propose to explore the regulation of nucleotidedependent channel gating by kinases, pH and phospolipids, and the stoichiometry of channel subunits. Second, because recent studies have identified ROMK deletions in Bartter's syndrome, a condition of renal sodium (Na) and K+ wasting, we plan to study the effects of loss of apical potassium channels in a ROMK knock-but model. We will also examine alternative transport mechanisms of K+ secretion. Patch-clamp and whole-cell current measurements will be carried out in native tubules and in an oocyte expression system, and tubule perfusion studies in ROMK knock-out mice.
| Hebert, Steven C; Desir, Gary; Giebisch, Gerhard et al. (2005) Molecular diversity and regulation of renal potassium channels. Physiol Rev 85:319-71 |
| Lin, Dao-Hong; Sterling, Hyacinth; Wang, Zhijian et al. (2005) ROMK1 channel activity is regulated by monoubiquitination. Proc Natl Acad Sci U S A 102:4306-11 |
| O'Connell, Anthony D; Leng, Qiang; Dong, Ke et al. (2005) Phosphorylation-regulated endoplasmic reticulum retention signal in the renal outer-medullary K+ channel (ROMK). Proc Natl Acad Sci U S A 102:9954-9 |
| 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 |
| Lu, Ming; Wang, Tong; Yan, Qingshang et al. (2004) ROMK is required for expression of the 70-pS K channel in the thick ascending limb. Am J Physiol Renal Physiol 286:F490-5 |
| Giebisch, Gerhard (2004) Challenges to potassium metabolism: internal distribution and external balance. Wien Klin Wochenschr 116:353-66 |
| Giebisch, Gerhard; Hebert, Steven C; Wang, Wen-Hui (2003) New aspects of renal potassium transport. Pflugers Arch 446:289-97 |
| Lu, Ming; Wang, Tong; Yan, Qingshang et al. (2002) Absence of small conductance K+ channel (SK) activity in apical membranes of thick ascending limb and cortical collecting duct in ROMK (Bartter's) knockout mice. J Biol Chem 277:37881-7 |
| Vanoye, Carlos G; MacGregor, Gordon G; Dong, Ke et al. (2002) The carboxyl termini of K(ATP) channels bind nucleotides. J Biol Chem 277:23260-70 |
| Dong, K; Xu, J; Vanoye, C G et al. (2001) An amino acid triplet in the NH2 terminus of rat ROMK1 determines interaction with SUR2B. J Biol Chem 276:44347-53 |
Showing the most recent 10 out of 12 publications
