Role of KCNE1-dependent K+ fluxes in mouse proximal tubule.
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.
Vallon
Volker
V
Department of Pharmacology, University of Tuebingen, Tuebingen, Germany.
Grahammer
Florian
F
Department of Physiology, University of Freiburg, Freiburg, Germany.
Richter
Kerstin
K
Department of Pharmacology, University of Tuebingen, Tuebingen, Germany.
Bleich
Markus
M
Department of Physiology, University of Freiburg, Freiburg, Germany.
Lang
Florian
F
Department of Physiology, University of Tuebingen, Tuebingen, Germany.
Barhanin
Jacques
J
CNRS Institut de Pharmacologie Moleculaire et Cellulaire, Valbonne, France.
Völkl
Harald
H
Department of Physiology, University of Innsbruck, Innsbruck, Austria.
Warth
Richard
R
CNRS Institut de Pharmacologie Moleculaire et Cellulaire, Valbonne, France.
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
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