Role of KCNE1-Dependent K+ Fluxes in Mouse Proximal Tubule : Journal of the American Society of Nephrology (original) (raw)

Cell and Transport Physiology

VALLON, VOLKER*; GRAHAMMER, FLORIAN‡; RICHTER, KERSTIN*; BLEICH, MARKUS‡; LANG, FLORIAN†; BARHANIN, JACQUES§; VÖLKL, HARALD¶; WARTH, RICHARD§

*Department of Pharmacology, University of Tuebingen, Tuebingen, Germany

†Department of Physiology, University of Tuebingen, Tuebingen, Germany

‡Department of Physiology, University of Freiburg, Freiburg, Germany

§CNRS Institut de Pharmacologie Moleculaire et Cellulaire, Valbonne, France

¶Department of Physiology, University of Innsbruck, Innsbruck, Austria.

Correspondence to Dr. Volker Vallon, Department of Pharmacology, University of Tübingen, Wilhelmstr. 56, D-72074 Tübingen, Germany. Phone: 07071-297 2271; Fax: 07071-29 4942; E-mail: [email protected]

Accepted March 3, 2001

Received January 12, 2001

Abstract

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.