title: Increasing plasma [K+] by intravenous potassium infusion reduces NCC phosphorylation and drives kaliuresis and natriuresis.
abstract: Dietary potassium loading results in rapid kaliuresis, natriuresis, and diuresis associated with reduced phosphorylation (p) of the distal tubule Na(+)-Cl(-) cotransporter (NCC). Decreased NCC-p inhibits NCC-mediated Na(+) reabsorption and shifts Na(+) downstream for reabsorption by epithelial Na(+) channels (ENaC), which can drive K(+) secretion. Whether the signal is initiated by ingesting potassium or a rise in plasma K(+) concentration ([K(+)]) is not understood. We tested the hypothesis, in male rats, that an increase in plasma [K(+)] is sufficient to reduce NCC-p and drive kaliuresis. After an overnight fast, a single 3-h 2% potassium (2%K) containing meal increased plasma [K(+)] from 4.0 ± 0.1 to 5.2 ± 0.2 mM; increased urinary K(+), Na(+), and volume excretion; decreased NCC-p by 60%; and marginally reduced cortical Na(+)-K(+)-2Cl(-) cotransporter (NKCC) phosphorylation 25% (P = 0.055). When plasma [K(+)] was increased by tail vein infusion of KCl to 5.5 ± 0.1 mM over 3 h, significant kaliuresis and natriuresis ensued, NCC-p decreased by 60%, and STE20/SPS1-related proline alanine-rich kinase (SPAK) phosphorylation was marginally reduced 35% (P = 0.052). The following were unchanged at 3 h by either the potassium-rich meal or KCl infusion: Na(+)/H(+) exchanger 3 (NHE3), NHE3-p, NKCC, ENaC subunits, and renal outer medullary K(+) channel. In summary, raising plasma [K(+)] by intravenous infusion to a level equivalent to that observed after a single potassium-rich meal triggers renal kaliuretic and natriuretic responses, independent of K(+) ingestion, likely driven by decreased NCC-p and activity sufficient to shift sodium reabsorption downstream to where Na(+) reabsorption and flow drive K(+) secretion.
authors.affiliation: Cell and Neurobiology, Keck School of Medicine of USC, 1333 San Pablo St Los Angeles, CA 90033. mcdonoug@usc.edu.
authors.forename: Srinivas
authors.initials: S
authors.lastname: Rengarajan
authors.forename: Donna H
authors.initials: DH
authors.lastname: Lee
authors.forename: Young Taek
authors.initials: YT
authors.lastname: Oh
authors.forename: Eric
authors.initials: E
authors.lastname: Delpire
authors.forename: Jang H
authors.initials: JH
authors.lastname: Youn
authors.forename: Alicia A
authors.initials: AA
authors.lastname: McDonough
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D053503:Epithelial Sodium Channels / Q000378:metabolism; D006947:Hyperkalemia / Q000097:blood* / Q000139:chemically induced / Q000503:physiopathology / Q000652:urine; D007262:Infusions, Intravenous; D007668:Kidney / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D009318:Natriuresis; D010766:Phosphorylation; D011188:Potassium / Q000008:administration & dosage / Q000097:blood* / Q000652:urine; D015221:Potassium Channels / Q000378:metabolism; D017419:Potassium, Dietary / Q000097:blood / Q000652:urine; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000097:blood / Q000652:urine*; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism; D064486:Solute Carrier Family 12, Member 3 / Q000378:metabolism; D013997:Time Factors
chemical_list: D053503:Epithelial Sodium Channels; D015221:Potassium Channels; D017419:Potassium, Dietary; C578876:Slc12a3 protein, rat; C000613387:Slc9a3 protein, rat; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers; D064486:Solute Carrier Family 12, Member 3; D012964:Sodium; C116037:PAS domain kinases; D017346:Protein Serine-Threonine Kinases; D011188:Potassium
keywords: feedback; hyperkalemia; potassium homeostasis; sodium transport regulation