Na+ pump inhibition downregulates an ATP-sensitive K+ channel in rabbit proximal convoluted tubule
Hurst, A.M.; Beck, J.S.; Laprade, R.; Lapointe, J.Y.
American Journal of Physiology 264(4 Pt 2): F760-F764
1993
ISSN/ISBN: 0002-9513 PMID: 8386476 Document Number: 418428
In several epithelial and nonepithelial tissues a functional link between the basolateral Na+-K+-adenosinetriphosphatase (Na+-K+-ATPase) and a basolateral K+ conductance has been established. However, the nature of this link is unclear. We have previously identified a K+ channel on the basolateral membrane of the proximal convoluted tubule perfused in vitro, the activity of which is increased by stimulation of Na+ transport . In the present study we investigate whether basolateral membrane K+ channel activity is tightly coupled to Na+-K+-ATPase activity. In cell-attached patches (150 mM K+ pipette), following stimulation of channel activity by addition of Na+-cotransported solutes to the tubule lumen, mean channel open probability (NPo) was reduced from 0.35 ± 0.09 to 0.14 ± 0.06 (n = 7, P < 0.05) by blocking the Na+-K+-ATPase with 100 mM strophanthidin. In excised patches the channel was reversibly blocked by 2 mM ATP from the cytosolic face of the patch, such that NPo fell to 20.1 ± 7.0% (n = 5, P < 0.001) of control and recovered to 52.2 ± 11.2% (n = 5, P < 0.05) after washout of ATP. Diazoxide, a putative opener of ATP-sensitive K+ channels, when added to the bathing solution of an unstimulated tubule (microperfused in the absence of Na+-cotransported solutes), increased NPo from 0.046 ± 0.035 to 0.44 ± 0.2 (n= 6, P < 0.05). These results demonstrate that the Na+-K+-ATPase is functionally coupled to a basolateral membrane K+ channel through an intracellular messenger, possibly ATP. Reprinted by permission of the publisher.