title: The renal TRPV4 channel is essential for adaptation to increased dietary potassium.
abstract: To maintain potassium homeostasis, kidneys exert flow-dependent potassium secretion to facilitate kaliuresis in response to elevated dietary potassium intake. This process involves stimulation of calcium-activated large conductance maxi-K (BK) channels in the distal nephron, namely the connecting tubule and the collecting duct. Recent evidence suggests that the TRPV4 channel is a critical determinant of flow-dependent intracellular calcium elevations in these segments of the renal tubule. Here, we demonstrate that elevated dietary potassium intake (five percent potassium) increases renal TRPV4 mRNA and protein levels in an aldosterone-dependent manner and causes redistribution of the channel to the apical plasma membrane in native collecting duct cells. This, in turn, leads to augmented TRPV4-mediated flow-dependent calcium ion responses in freshly isolated split-opened collecting ducts from mice fed the high potassium diet. Genetic TRPV4 ablation greatly diminished BK channel activity in collecting duct cells pointing to a reduced capacity to excrete potassium. Consistently, elevated potassium intake induced hyperkalemia in TRPV4 knockout mice due to deficient renal potassium excretion. Thus, regulation of TRPV4 activity in the distal nephron by dietary potassium is an indispensable component of whole body potassium balance.
authors.affiliation: Department of Integrative Biology and Pharmacology, the University of Texas Health Science Center at Houston, Houston, Texas, USA; Department of Physiology, Medical College of Georgia, Augusta University, Augusta, Georgia, USA.
authors.forename: Mykola V
authors.initials: MV
authors.lastname: Mamenko
authors.affiliation: Department of Integrative Biology and Pharmacology, the University of Texas Health Science Center at Houston, Houston, Texas, USA.
authors.forename: Nabila
authors.initials: N
authors.lastname: Boukelmoune
authors.affiliation: Department of Integrative Biology and Pharmacology, the University of Texas Health Science Center at Houston, Houston, Texas, USA; Institute of Cytology, Russian Academy of Sciences, St. Petersburg, Russian Federation.
authors.forename: Viktor N
authors.initials: VN
authors.lastname: Tomilin
authors.affiliation: Department of Integrative Biology and Pharmacology, the University of Texas Health Science Center at Houston, Houston, Texas, USA.
authors.forename: Oleg L
authors.initials: OL
authors.lastname: Zaika
authors.affiliation: Department of Veterinary Medicine and Surgery, the University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: V Behrana
authors.initials: VB
authors.lastname: Jensen
authors.affiliation: Department of Integrative Biology and Pharmacology, the University of Texas Health Science Center at Houston, Houston, Texas, USA.
authors.forename: Roger G
authors.initials: RG
authors.lastname: O'Neil
authors.affiliation: Department of Integrative Biology and Pharmacology, the University of Texas Health Science Center at Houston, Houston, Texas, USA. Electronic address: Oleh.M.Pochynyuk@uth.tmc.edu.
authors.forename: Oleh M
authors.initials: OM
authors.lastname: Pochynyuk
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D002118:Calcium / Q000378:metabolism; D020022:Genetic Predisposition to Disease; D006706:Homeostasis; D006947:Hyperkalemia / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D007684:Kidney Tubules / Q000378:metabolism* / Q000503:physiopathology; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000378:metabolism; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010641:Phenotype; D017419:Potassium, Dietary / Q000008:administration & dosage / Q000378:metabolism*; D018161:Receptors, Mineralocorticoid / Q000378:metabolism; D065667:Renal Elimination; D050916:TRPV Cation Channels / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
chemical_list: D051036:Large-Conductance Calcium-Activated Potassium Channels; D017419:Potassium, Dietary; D018161:Receptors, Mineralocorticoid; D050916:TRPV Cation Channels; C486576:Trpv4 protein, mouse; D002118:Calcium
keywords: BK channels; [Ca(2+)](i) signaling; aldosterone; distal nephron; flow-induced potassium secretion