title: Role of KCNE1-dependent K+ fluxes in mouse proximal tubule.
abstract: The electrochemical gradient for K+ across the luminal membrane of the proximal tubule favors K+ fluxes to the lumen. Here it was demonstrated by immunohistochemistry that KCNE1 and KCNQ1, which form together the slowly activated component of the delayed rectifying K+ current in the heart, also colocalize in the luminal membrane of proximal tubule in mouse kidney. Micropuncture experiments revealed a reduced K+ concentration in late proximal and early distal tubular fluid as well as a reduced K+ delivery to these sites in KCNE1 knockout (-/-), compared with wild-type (+/+) mice. These observations would be consistent with KCNE1-dependent K+ fluxes to the lumen in proximal tubule. Electrophysiological studies in isolated perfused proximal tubules indicated that this K+ flux is essential to counteract membrane depolarization due to electrogenic Na+-coupled transport of glucose or amino acids. Clearance studies revealed an enhanced fractional urinary excretion of fluid, Na+, Cl-, and glucose in KCNE1 -/- compared with KCNE1 +/+ mice that may relate to an attenuated transport in proximal tubule and contribute to volume depletion in these mice, as indicated by higher hematocrit values.
authors.affiliation: Department of Pharmacology, University of Tuebingen, Tuebingen, Germany.
authors.forename: Volker
authors.initials: V
authors.lastname: Vallon
authors.affiliation: Department of Physiology, University of Freiburg, Freiburg, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Grahammer
authors.affiliation: Department of Pharmacology, University of Tuebingen, Tuebingen, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Richter
authors.affiliation: Department of Physiology, University of Freiburg, Freiburg, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Bleich
authors.affiliation: Department of Physiology, University of Tuebingen, Tuebingen, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Lang
authors.affiliation: CNRS Institut de Pharmacologie Moleculaire et Cellulaire, Valbonne, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Barhanin
authors.affiliation: Department of Physiology, University of Innsbruck, Innsbruck, Austria.
authors.forename: Harald
authors.initials: H
authors.lastname: Völkl
authors.affiliation: CNRS Institut de Pharmacologie Moleculaire et Cellulaire, Valbonne, France.
authors.forename: Richard
authors.initials: R
authors.lastname: Warth
mesh_terms: D000584:Amiloride / Q000494:pharmacology; D000758:Anesthesia; D000818:Animals; D004594:Electrophysiology; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D051656:KCNQ Potassium Channels; D051657:KCNQ1 Potassium Channel; D007687:Kidney Tubules, Proximal / Q000378:metabolism* / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics; D010477:Perfusion; D011188:Potassium / Q000378:metabolism*; D015221:Potassium Channels / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D024642:Potassium Channels, Voltage-Gated; D011677:Punctures
chemical_list: D051656:KCNQ Potassium Channels; D051657:KCNQ1 Potassium Channel; C496910:Kcnq1 protein, mouse; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; C059983:potassium channel protein I(sk); D000584:Amiloride; D011188:Potassium