application) Disturbances of potassium homeostasis can result in fatal consequences such as cardiac arrest. The kidney is a vital organ that maintains serum potassium concentration in a very narrow range. To achieve this, renal epithelial cells are equipped with membrane transporters such as Na-ATPase and K channels. The exact mechanism of K absorption and secretion in the kidney is not completely understood, however, recent progress suggests that potassium channels may play an important role in the process. In addition to inward rectifier K channels, voltage-gated K channels are also expressed in kidney. Dr. Gary Desir's laboratory has identified several such channels. Two of these have been extensively characterized: Kv1.3 and KCNA10. Although the precise physiological role of these channels in renal K homeostasis is unclear, it is postulated that Kv1.3, in conjunction with ATP-sensitive KATP channels, mediates K exit into interstitium where K can be returned to blood stream or accumulated and recycled back into the cell by Na+,K+-ATPase pump. KCNA10 may participate in K transport, the regulation of vascular tone, the cardiac action potential, and cortisol secretion. To test these hypotheses, I will examine the sub-cellular localization of Kv1.3 in the renal epithelia, and study the Kv1.3 function in vivo using gene-targeting.
The Specific Aims of the project are: (1) Localization of Kv1.3 in renal epithelial cells. (2) Generation of Kv1.3-deficient mice. (3) Characterization of the K0.3-deficient mice. (4) Generation of KCNA10 knockout mouse and Kv1.3/KCNA10 double knockout mouse.
| Li, Guoyong; Xu, Jianchao; Wang, Peili et al. (2008) Catecholamines regulate the activity, secretion, and synthesis of renalase. Circulation 117:1277-82 |
| Li, Yanyan; Wang, Peili; Xu, Jianchao et al. (2007) Regulation of insulin secretion and GLUT4 trafficking by the calcium sensor synaptotagmin VII. Biochem Biophys Res Commun 362:658-64 |
| Li, Yanyan; Wang, Peili; Xu, Jianchao et al. (2006) Voltage-gated potassium channel Kv1.3 regulates GLUT4 trafficking to the plasma membrane via a Ca2+-dependent mechanism. Am J Physiol Cell Physiol 290:C345-51 |
| Xu, Jianchao; Li, Guoyong; Wang, Peili et al. (2005) Renalase is a novel, soluble monoamine oxidase that regulates cardiac function and blood pressure. J Clin Invest 115:1275-80 |
| Xu, Jianchao; Wang, Peili; Li, Yanyan et al. (2004) The voltage-gated potassium channel Kv1.3 regulates peripheral insulin sensitivity. Proc Natl Acad Sci U S A 101:3112-7 |
