The kidney maintains the appropriate amounts of potassium in the body by matching the amounts of salt excreted to those which are in the diet. The final regulation of K+ balance is thought to occur in the collecting tubule. Here, the amount of K+ secreted or absorbed depends on the activities of apical K+ channels. Previous work showed that when dietary K+ is high, the density of apical K+ channels is increased through a mechanism which is independent of aldosterone. In the proposed research they will explore this regulatory process further, focusing on the systems controlling the K+ channels. Experimental studies will involve the use of a combination of electrophysiological and molecular biological approaches. They will explore in detail the relationship between K+ channel density and dietaryes, they will examine the time course and load dependence of the upregulation of conducting K+ channel density. They will also test whether the channels are downregulated in animals on a K+-restricted diet. The principal investigator will test the hypothesis that increased levels of mRNA underly the control of the density of conducting channels using quantitative in situ hybridization techniques. The principal investigator will use antibodies raised against the K+ channel to map the sites of apical K+ channel expression and to assess the role of changes in the amount of K+ channel protein in the regulatory process. He will also explore the relationship between the long-term regulation of the K+ channels with more short-term processes. These will include both regulation through cAMP and PKA, and channel activation by acute elevation of extracellular K+. The biophysical and molecular basis for the latter effect will also be studied using the Xenopus oocyte expression system. This research should help illuminate how K+ transport by the distal nephron is regulated during health (changes in diet) and disease (e.g. renal insufficiency). It will also help to clarify how Na+ and K+ transport can be regulated separately in the collecting tubule to maintain blood volume and pressure as well as plasma K+ concentration within narrow limits.
| Yang, Lei; Frindt, Gustavo; Lang, Florian et al. (2017) SGK1-dependent ENaC processing and trafficking in mice with high dietary K intake and elevated aldosterone. Am J Physiol Renal Physiol 312:F65-F76 |
| Frindt, Gustavo; Gravotta, Diego; Palmer, Lawrence G (2016) Regulation of ENaC trafficking in rat kidney. J Gen Physiol 147:217-27 |
| Frindt, Gustavo; Palmer, Lawrence G (2015) Acute effects of aldosterone on the epithelial Na channel in rat kidney. Am J Physiol Renal Physiol 308:F572-8 |
| Palmer, Lawrence G; Schnermann, Jürgen (2015) Integrated control of Na transport along the nephron. Clin J Am Soc Nephrol 10:676-87 |
| Patel, Ankit B; Yang, Lei; Deng, Su et al. (2014) Feedback inhibition of ENaC: acute and chronic mechanisms. Channels (Austin) 8:444-51 |
| Yang, Lei; Palmer, Lawrence G (2014) Ion conduction and selectivity in acid-sensing ion channel 1. J Gen Physiol 144:245-55 |
| Frindt, Gustavo; Li, Hui; Sackin, Henry et al. (2013) Inhibition of ROMK channels by low extracellular K+ and oxidative stress. Am J Physiol Renal Physiol 305:F208-15 |
| Yang, Lei; Edvinsson, Johan; Sackin, Henry et al. (2012) Ion selectivity and current saturation in inward-rectifier K+ channels. J Gen Physiol 139:145-57 |
| Yang, Lei; Edvinsson, Johan; Palmer, Lawrence G (2012) Interactions of external K+ and internal blockers in a weak inward-rectifier K+ channel. J Gen Physiol 140:529-40 |
| Sackin, Henry; Nanazashvili, Mikheil; Li, Hui et al. (2012) Residues at the outer mouth of Kir1.1 determine K-dependent gating. Biophys J 102:2742-50 |
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