Expression and insights on function of potassium channel TWIK-1 in mouse kidney.
Renal distribution and function of TWIK-1, a member of the two-pore-domain potassium channel family, was studied in mouse kidney. TWIK-1 is expressed in apical and subapical localizations of proximal tubule and cytoplasmic sites of thin and thick ascending limbs, distal convoluted tubules and medullary collecting duct. Studies in mice lacking intact TWIK-1 (twik-1 -/-) and wild-type mice (twik-1 +/+) revealed an attenuated ability to increase renal phosphate (Pi) reabsorption and stabilize plasma Pi concentration in response to a low Pi diet in twik-1 -/- mice. Western blot analysis and immunohistochemistry for the electrogenic 3Na(+)-1HPO(4) (2-)-cotransporter NaPi-2a revealed a reduced reno-cortical expression in twik-1 -/- mice under these conditions. Under normal diet, twik-1 -/- mice presented lower urinary flow rates. Acute pharmacologic blockade of the vasopressin V(2)-receptor revealed both an attenuated diuretic response and an attenuated internalization of aquaporin-2 in the inner medullary collecting duct in twik-1 -/- versus +/+ mice. In summary, mice deficient for TWIK-1 presented impaired regulation of (i) Pi transport in proximal tubule and (ii) water transport in medullary collecting duct. TWIK-1 may contribute to membrane trafficking/expression of transport molecules in proximal tubule and medullary collecting duct, and possibly other renal sites of expression.
Nie
Xin
X
Institute of Pharmacology and Toxicology, University of Tübingen, Germany.
Arrighi
Isabelle
I
Kaissling
Brigitte
B
Pfaff
Imke
I
Mann
Jeffrey
J
Barhanin
Jacques
J
Vallon
Volker
V
D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists; D051399:Aquaporin 2 / Q000378:metabolism; D015870:Gene Expression; D007679:Kidney Medulla / Q000378:metabolism; D007684:Kidney Tubules / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010710:Phosphates / Q000378:metabolism; D024683:Potassium Channels, Tandem Pore Domain / Q000502:physiology*; D050613:Sodium-Phosphate Cotransporter Proteins, Type IIa / Q000378:metabolism; D014556:Urine
D065092:Antidiuretic Hormone Receptor Antagonists; D051399:Aquaporin 2; C486372:Kcnk1 protein, mouse; D010710:Phosphates; D024683:Potassium Channels, Tandem Pore Domain; D050613:Sodium-Phosphate Cotransporter Proteins, Type IIa