To preserve plasma K levels, the kidney excretes K in amounts that exactly match K intake. This is done at least in part by modulating the amount of K secreted into the urine through apical membrane K channels in the distal nephron. The movement of K through such channels will be studied both in renal tubular cells themselves and in Xenopus oocytes expressing the cloned renal K channel ROMK. The molecular determinants of ion conduction through the channels will be examined by exchanging parts of the C-terminus of ROMK with that of a related channel (IRK 1) which has different permeation properties. The role of the C-terminus will be further studied by assessing the ability of quaternary ammonium ions to enter the pore from the cytoplasmic side, and the ability of cysteine-modifying reagents to inhibit the function of channels with cysteines added to the C-terminus. The role of this part of the protein in the gating of the channel by internal pH and external K will also be explored by testing the ability of the channels to close when the cytoplasmic end is blocked by quaternary ammonium ions or polyamines. The basis for ion selectivity among K, Rb, TI and NH4 will be studied by measuring conductances with increasing concentrations of the various ions. Results will be compared with predictions made from discrete barrier models of ion permeation. The role of ROMK channels in mediating K secretion will be assessed by (1) measuring net K flux through the channels under various conditions of luminal K concentration and luminal membrane voltage (2) y measuring conducting channel densities under different physiological conditions and (3) applying this information to the development of a quantitative model of K transport by distal nephron segments. We will investigate the types of K channels (SK or ROMK channels, BK or Ca-activated K channels) expressed in the connecting tubule, a segment s previously demonstarted to take part in K secretion. Regulation of channels in this segment will be examined with particular focus on the role of dietary K (in vivo) and cAMP and glucagon-like peptide (in vitro). The possibility that hormones may promote the movement of channels between intracellular and plasma membrane compartments will be evaluated using immunocytochemistry of isolated renal tubules.
| 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 |
Showing the most recent 10 out of 70 publications
