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10.1038/ki.2015.289 http://scihub22266oqcxt.onion/10.1038/ki.2015.289 26422504!4814375!26422504     free     free     free Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Kidney+Int 2016 ; 89 (1): 127-34 Nephropedia Template TP {{tp|p=26422504|t=2016. Unique chloride-sensing properties of WNK4 permit the distal nephron to modulate potassium homeostasis |pdf=|usr=}}{{26422504}} gab.com Text Unique chloride-sensing properties of WNK4 permit the distal nephron to modulate potassium homeostasis JO: Kidney Int http://www.kidney.de/pget.php?&tw=1&pmid=26422504 #FOAvip Dietary potassium deficiency activates thiazide-sensitive sodium chloride cotransport along the distal nephron. This may explain, in part, the hypertension and cardiovascular mortality observed in individuals who consume a low-potassium diet. Recent data suggest that plasma potassium affects the distal nephron directly by influencing intracellular chloride, an inhibitor of the with-no-lysine kinase (WNK)-Ste20p-related proline- and alanine-rich kinase (SPAK) pathway. As previous studies used extreme dietary manipulations, we sought to determine whether the relationship between potassium and NaCl cotransporter (NCC) is physiologically relevant and clarify the mechanisms involved. We report that modest changes in both dietary and plasma potassium affect NCC in vivo. Kinase assay studies showed that chloride inhibits WNK4 kinase activity at lower concentrations than it inhibits activity of WNK1 or WNK3. Also, chloride inhibited WNK4 within the range of distal cell chloride concentration. Mutation of a previously identified WNK chloride-binding motif converted WNK4 effects on SPAK from inhibitory to stimulatory in mammalian cells. Disruption of this motif in WNKs 1, 3, and 4 had different effects on NCC, consistent with the three WNKs having different chloride sensitivities. Thus, potassium effects on NCC are graded within the physiological range, which explains how unique chloride-sensing properties of WNK4 enable it to mediate effects of potassium on NCC in vivo. Twit Text FOAVip Unique chloride-sensing properties of WNK4 permit the distal nephron to modulate potassium homeostasis ????Kidney Int http://www.kidney.de/pget.php?&tw=1&pmid=26422504 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=26422504 #FOAvip English Wikipedia <ref>{{Cite pmid|26422504}}</ref> Unique chloride-sensing properties of WNK4 permit the distal nephron to modulate potassium homeostasis #MMPMID26422504 Terker AS; Zhang C; Erspamer KJ; Gamba G; Yang CL; Ellison DH Kidney Int 2016[Jan]; 89 (1): 127-34 PMID26422504show ga Dietary potassium deficiency activates thiazide-sensitive sodium chloride cotransport along the distal nephron. This may explain, in part, the hypertension and cardiovascular mortality observed in individuals who consume a low-potassium diet. Recent data suggest that plasma potassium affects the distal nephron directly by influencing intracellular chloride, an inhibitor of the with-no-lysine kinase (WNK)-Ste20p-related proline- and alanine-rich kinase (SPAK) pathway. As previous studies used extreme dietary manipulations, we sought to determine whether the relationship between potassium and NaCl cotransporter (NCC) is physiologically relevant and clarify the mechanisms involved. We report that modest changes in both dietary and plasma potassium affect NCC in vivo. Kinase assay studies showed that chloride inhibits WNK4 kinase activity at lower concentrations than it inhibits activity of WNK1 or WNK3. Also, chloride inhibited WNK4 within the range of distal cell chloride concentration. Mutation of a previously identified WNK chloride-binding motif converted WNK4 effects on SPAK from inhibitory to stimulatory in mammalian cells. Disruption of this motif in WNKs 1, 3, and 4 had different effects on NCC, consistent with the three WNKs having different chloride sensitivities. Thus, potassium effects on NCC are graded within the physiological range, which explains how unique chloride-sensing properties of WNK4 enable it to mediate effects of potassium on NCC in vivo. |*Homeostasis[MESH] |Animals[MESH] |Chlorides/*metabolism[MESH] |HEK293 Cells[MESH] |Humans[MESH] |Intracellular Signaling Peptides and Proteins/genetics/metabolism[MESH] |Kidney Tubules, Distal/cytology/physiology[MESH] |Mice[MESH] |Mice, Inbred BALB C[MESH] |Mice, Inbred C57BL[MESH] |Minor Histocompatibility Antigens/genetics/metabolism[MESH] |Mutation[MESH] |Nephrons/physiology[MESH] |Phosphorylation/genetics[MESH] |Potassium, Dietary/administration & dosage[MESH] |Potassium/*blood/metabolism[MESH] |Protein Serine-Threonine Kinases/genetics/*metabolism[MESH] |Solute Carrier Family 12, Member 3/*metabolism[MESH]Unique chloride-sensing properties of WNK4 permit the distal nephron t(epmc).pdf DeepDyve Pubget Overpricing