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© The Rockefeller University Press, 0022-1295/1998//139/ $5.00
Journal of General Physiology, Volume 111, Number 1, 1998

Article

Properties of an Inwardly Rectifying ATP-sensitive K+ Channel in the Basolateral Membrane of Renal Proximal Tubule

Ulrich R. Mauerer*, Emile L. Boulpaep*, and Alan S. Segal*,{ddagger}

From the * Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, Connecticut 06520; and {ddagger} Department of Medicine, University of Vermont, Burlington, Vermont 05401

The potassium conductance of the basolateral membrane (BLM) of proximal tubule cells is a critical regulator of transport since it is the major determinant of the negative cell membrane potential and is necessary for pump-leak coupling to the Na+,K+-ATPase pump. Despite this pivotal physiological role, the properties of this conductance have been incompletely characterized, in part due to difficulty gaining access to the BLM. We have investigated the properties of this BLM K+ conductance in dissociated, polarized Ambystoma proximal tubule cells. Nearly all seals made on Ambystoma cells contained inward rectifier K+ channels ({gamma}slope, in = 24.5 ± 0.6 pS, {gamma}chord, out = 3.7 ± 0.4 pS). The rectification is mediated in part by internal Mg2+. The open probability of the channel increases modestly with hyperpolarization. The inward conducting properties are described by a saturating binding–unbinding model. The channel conducts Tl+ and K+, but there is no significant conductance for Na+, Rb+, Cs+, Li+, NH4+, or Cl–. The channel is inhibited by barium and the sulfonylurea agent glibenclamide, but not by tetraethylammonium. Channel rundown typically occurs in the absence of ATP, but cytosolic addition of 0.2 mM ATP (or any hydrolyzable nucleoside triphosphate) sustains channel activity indefinitely. Phosphorylation processes alone fail to sustain channel activity. Higher doses of ATP (or other nucleoside triphosphates) reversibly inhibit the channel. The K+ channel opener diazoxide opens the channel in the presence of 0.2 mM ATP, but does not alleviate the inhibition of millimolar doses of ATP. We conclude that this K+ channel is the major ATP-sensitive basolateral K+ conductance in the proximal tubule.

Key Words: ion channel • kidney • patch-clamp • sulfonylurea • epithelia

Address correspondence to Alan S. Segal, Department of Medicine, University of Vermont, 55A South Park Drive, Colchester, VT 05446. Fax: 802-656-8915; E-mail: asegal{at}zoo.uvm.edu


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